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Sample records for amino metabolism modifications

  1. Amino Acid Metabolism Disorders

    Science.gov (United States)

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup ...

  2. Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

    OpenAIRE

    Pujos-Guillot, Estelle; Pickering, Gisèle; Lyan, Bernard; Ducheix, Gilles; Brandolini-Bunlon, Marion; Glomot, Françoise; Dardevet, Dominique; Dubray, Claude; PAPET, Isabelle

    2011-01-01

    Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on ...

  3. Expression of Cell-Surface Marker ABCB5 Causes Characteristic Modifications of Glucose, Amino Acid and Phospholipid Metabolism in the G3361 Melanoma-Initiating Cell Line.

    Science.gov (United States)

    Lutz, Norbert W; Banerjee, Pallavi; Wilson, Brian J; Ma, Jie; Cozzone, Patrick J; Frank, Markus H

    2016-01-01

    We present a pilot study aimed at determining the effects of expression of ATP-binding cassette member B5 (ABCB5), a previously described marker for melanoma-initiating cells, on cellular metabolism. Metabolic profiles for two groups of human G3361 melanoma cells were compared, i.e. wildtype melanoma cells with intact ABCB5 expression (ABCB5-WT) and corresponding melanoma cell variants with inhibited ABCB5 expression, through shRNA-mediated gene knockdown (ABCB5-KD). A comprehensive metabolomic analysis was performed by using proton and phosphorus NMR spectroscopy of cell extracts to examine water-soluble metabolites and lipids. Parametric and non-parametric statistical analysis of absolute and relative metabolite levels yielded significant differences for compounds involved in glucose, amino acid and phospholipid (PL) metabolism. By contrast, energy metabolism was virtually unaffected by ABCB5 expression. The sum of water-soluble metabolites per total protein was 17% higher in ABCB5-WT vs. ABCB5-KD G3361 variants, but no difference was found for the sum of PLs. Enhanced abundance was particularly pronounced for lactate (+ 23%) and alanine (+ 26%), suggesting an increase in glycolysis and potentially glutaminolysis. Increases in PL degradation products, glycerophosphocholine and glycerophosphoethanolamine (+ 85 and 123%, respectively), and redistributions within the PL pool suggested enhanced membrane PL turnover as a consequence of ABCB5 expression. The possibility of glycolysis modulation by an ABCB5-dependent IL1β-mediated mechanism was supported by functional studies employing monoclonal antibody (mAb)-dependent ABCB5 protein inhibition in wildtype G3361 melanoma cells. Our metabolomic results suggest that the underlying biochemical pathways may offer targets for melanoma therapy, potentially in combination with other treatment forms. PMID:27560924

  4. Long-term Temozolomide Treatment Induces Marked Amino Metabolism Modifications and an Increase in TMZ Sensitivity in Hs683 Oligodendroglioma Cells

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    Delphine Lamoral-Theys

    2010-01-01

    Full Text Available Gliomas account for more than 50% of all primary brain tumors. The worst prognosis is associated with gliomas of astrocytic origin, whereas gliomas with an oligodendroglial origin offer higher sensitivity to chemotherapy, especially when oligodendroglioma cells display 1p19q deletions. Temozolomide (TMZ provides therapeutic benefits and is commonly used with radiotherapy in highly malignant astrocytic tumors, including glioblastomas. The actual benefits of TMZ during long-term treatment in oligodendroglioma patients have not yet been clearly defined. In this study, we have investigated the effects of such a long-term TMZ treatment in the unique Hs683 oligodendroglioma model. We have observed increased TMZ sensitivity of Hs683 orthotopic tumors that were previously treated in vitro with months of progressive exposure to increasing TMZ concentrations before being xenografted into the brains of immunocompromised mice. Whole-genome and proteomic analyses have revealed that this increased TMZ sensitivity of Hs683 oligodendroglioma cells previously treated for long periods with TMZ can be explained, at least partly, by a TMZ-induced p38-dependant dormancy state, which in turn resulted in changes in amino acid metabolism balance, in growth delay, and in a decrease in Hs683 oligodendroglioma cell-invasive properties. Thus, long-term TMZ treatment seems beneficial in this Hs683 oligodendroglioma model, which revealed itself unable to develop resistance against TMZ.

  5. Amino acid modifications on tRNA

    Institute of Scientific and Technical Information of China (English)

    Jing Yuan; Kelly Sheppard; Dieter S(o)ll

    2008-01-01

    The accurate formation of cognate aminoacyl-transfer RNAs (aa-tRNAs) is essential for the fidelity of translation.Most amino acids are esterified onto their cognate tRNA isoacceptors directly by aa.tRNA synthetases.However,in the case of four amino acids (Gin,Asn,Cys and Sec),aminoacyl-tRNAs are made through indirect pathways in many organisms across all three domains of life.The process begins with the charging ofnoncognate amino acids to tRNAs by a specialized synthetase in the case of Cys-tRNAcys formation or by synthetases with relaxed specificity,such as the non-discriminating glutamyl-tRNA,non-discriminating aspartyl-tRNA and seryl-tRNA synthetases.The resulting misacylated tRNAs are then converted to cognate pairs through transformation of the amino acids on the tRNA,which is catalyzed by a group of tRNA-dependent modifying enzymes,such as tRNA-dependent amidotransferases,Sep-tRNA:Cys-tRNA synthase,O-phosphoseryi-tRNA kinase and Sep-tRNA:Sec-tRNA synthase.The majority of these indirect pathways are widely spread in all domains of life and thought to be part of the evolutionary process.

  6. The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia.

    Science.gov (United States)

    Perkins, W J; Lanier, W L; Karlsson, B R; Milde, J H; Michenfelder, J D

    1989-09-25

    The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic

  7. Computational Methods for Modification of Metabolic Networks

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    Takeyuki Tamura

    2015-01-01

    Full Text Available In metabolic engineering, modification of metabolic networks is an important biotechnology and a challenging computational task. In the metabolic network modification, we should modify metabolic networks by newly adding enzymes or/and knocking-out genes to maximize the biomass production with minimum side-effect. In this mini-review, we briefly review constraint-based formalizations for Minimum Reaction Cut (MRC problem where the minimum set of reactions is deleted so that the target compound becomes non-producible from the view point of the flux balance analysis (FBA, elementary mode (EM, and Boolean models. Minimum Reaction Insertion (MRI problem where the minimum set of reactions is added so that the target compound newly becomes producible is also explained with a similar formalization approach. The relation between the accuracy of the models and the risk of overfitting is also discussed.

  8. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However....... However, this does not seem applicable for inflammatory diseases or human models of sepsis, in which the enhanced imbalance between these two processes is observed within an enhanced, normal or reduced muscle protein turnover.......PURPOSE OF REVIEW: This review highlights the role of cytokines, in particular tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in relation to the nature of human in-vivo muscle wasting in disease. RECENT FINDINGS: Infusion of human TNF-α and IL-6 in healthy individuals, acutely...

  9. Metabolism of amino acid amides in Pseudomonas putida ATCC 12633

    NARCIS (Netherlands)

    Hermes, H.F.M.; Croes, L.M.; Peeters, W.P.H.; Peters, P.J.H.; Dijkhuizen, L.

    1993-01-01

    The metabolism of the natural amino acid L-valine, the unnatural amino acids D-valine, and D-, L-phenylglycine (D-, L-PG), and the unnatural amino acid amides D-, L-phenylglycine amide (D, L-PG-NH2) and L-valine amide (L-Val-NH2) was studied in Pseudomonas putida ATCC 12633. The organism possessed c

  10. Disturbed amino acid metabolism in HIV: association with neuropsychiatric symptoms

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    Johanna M Gostner

    2015-07-01

    Full Text Available Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1-infected patients. Both essential amino acids, tryptophan and phenylalanine are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms such as development of depression, fatigue, and cognitive impairment.Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions.

  11. Natural toxins that affect plant amino acid metabolism

    Science.gov (United States)

    A diverse range of natural compounds interfere with the synthesis and other aspects of amino acid metabolism. Some are amino acid analogues, but most are not. This review covers a number of specific natural phytotoxic compounds by molecular target site. Inhibition of glutamine synthetase is of part...

  12. The gut microbiota modulates host amino acid and glutathione metabolism in mice

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias;

    2015-01-01

    The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from......, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism...... conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon...

  13. The Role of Microbial Amino Acid Metabolism in Host Metabolism

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    Evelien P. J. G. Neis

    2015-04-01

    Full Text Available Disruptions in gut microbiota composition and function are increasingly implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. The functional output of the gut microbiota, including short-chain fatty acids and amino acids, are thought to be important modulators underlying the development of these disorders. Gut bacteria can alter the bioavailability of amino acids by utilization of several amino acids originating from both alimentary and endogenous proteins. In turn, gut bacteria also provide amino acids to the host. This could have significant implications in the context of insulin resistance and type 2 diabetes mellitus, conditions associated with elevated systemic concentrations of certain amino acids, in particular the aromatic and branched-chain amino acids. Moreover, several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids, which also play a role in the development of obesity. In this review, we aim to compile the available evidence on the contribution of microbial amino acids to host amino acid homeostasis, and to assess the role of the gut microbiota as a determinant of amino acid and short-chain fatty acid perturbations in human obesity and type 2 diabetes mellitus.

  14. Metabolic Response of Pakchoi Leaves to Amino Acid Nitrogen

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-li; YU Wen-juan; ZHOU Qian; HAN Rui-feng; HUANG Dan-feng

    2014-01-01

    Different nitrogen (N) forms may cause changes in the metabolic profiles of plants. However, few studies have been conducted on the effects of amino acid-N on plant metabolic proifles. The main objective of this study was to identify primary metabolites associated with amino acid-N (Gly, Gln and Ala) through metabolic proifle analysis using gas chromatography-mass spectrometry (GC-MS). Plants of pakchoi (Brassica campestris L. ssp. chinensis L.), Huawang and Wuyueman cultivars, were grown with different nitrogen forms (i.e., Gly, Gln, Ala, NO3--N, and N starvation) applied under sterile hydroponic conditions. The fresh weight and plant N accumulation of Huawang were greater than those of Wuyueman, which indicates that the former exhibited better N-use efficiency than the latter. The physiological performances of the applied N forms were generally in the order of NO3--N>Gln>Gly>Ala. The metabolic analysis of leaf polar extracts revealed 30 amino acid N-responsive metabolites in the two pakchoi cultivars, mainly consisting of sugars, amino acids, and organic acids. Changes in the carbon metabolism of pakchoi leaves under amino acid treatments occurred via the accumulation of fructose, glucose, xylose, and arabinose. Disruption of amino acid metabolism resulted in accumulation of endogenous Gly in Gly treatment, Pro in Ala treatment, and Asn in three amino acid (Gly, Gln and Ala) treatments. By contrast, the levels of endogenous Gln and Leu decreased. However, this reduction varied among cultivars and amino acid types. Amino acid-N supply also affected the citric acid cycle, namely, the second stage of respiration, where leaves in Gly, Gln and Ala treatments contained low levels of malic, citric and succinic acids compared with leaves in NO3--N treatments. No signiifcant difference in the metabolic responses was observed between the two cultivars which differed in their capability to use N. The response of primary metabolites in pakchoi leaves to amino acid-N supply

  15. N-13 labeled amino acids: biodistribution, metabolism and dosimetric considerations

    International Nuclear Information System (INIS)

    With the growing interest in metabolic imaging and with the increasing number of cyclotron/PET facilities, more studies are being performed in animal and humans using short-lived positron-emitting radionuclides. Amino acids labeled either with N-13 or C-11 are one group of compounds being used to study in vivo regional organ (i.e., brain and heart) or tumor metabolism. Of the studies previously reported using C-11 or N-13 labeled amino acids (methionine, alanine, valine, glutamate, glutamine and tryptophan), imaging was restricted mainly to the organ or tissue of interest with little information obtained about the whole-bode distribution of the label. Such data are important for studying interorgan transport of amino acids and for determining accurate dosimetric measurements after intravenous injection of labeled amino acids. The goals of the authors study were to compare the distribution of several N-13 L-amino acids and N-13 ammonia in tumor-bearing mice and to determine the metabolic fate of the label in vivo. The following amino acids were enzymatically labeled using N-13 ammonia: glutamine, glutamate, methionine, α-aminobutyric acid, valine and leucine. 30 references, 2 figures, 14 tables

  16. Regulation of intestinal protein metabolism by amino acids.

    Science.gov (United States)

    Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

    2013-09-01

    Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

  17. Transcriptional regulation of central amino acid metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Larsen, Rasmus

    2005-01-01

    This thesis describes the functional characterisation of the transcriptional regulators GlnR, ArgR and AhrC of Lactococcus lactis, which are responsible for the control of genes involved in the metabolism of the amino acids glutamine, glutamate and arginine. A chromosomal glnR deletion mutant was ma

  18. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

    OpenAIRE

    M. Ryan Smith; Vayalil, Praveen K.; Fen Zhou; Benavides, Gloria A; Beggs, Reena R.; Hafez Golzarian; Bhavitavya Nijampatnam; Oliver, Patsy G.; Smith, Robin A.J.; Murphy, Michael P.; Velu, Sadanandan E.; Aimee Landar

    2016-01-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compo...

  19. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    Directory of Open Access Journals (Sweden)

    Marko Kreft

    2012-04-01

    Full Text Available Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.

  20. Role of mitochondrial transamination in branched chain amino acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hutson, S.M.; Fenstermacher, D.; Mahar, C.

    1988-03-15

    Oxidative decarboxylation and transamination of 1-/sup 14/C-branched chain amino and alpha-keto acids were examined in mitochondria isolated from rat heart. Transamination was inhibited by aminooxyacetate, but not by L-cycloserine. At equimolar concentrations of alpha-ketoiso(1-/sup 14/C)valerate (KIV) and isoleucine, transamination was increased by disrupting the mitochondria with detergent which suggests transport may be one factor affecting the rate of transamination. Next, the subcellular distribution of the aminotransferase(s) was determined. Branched chain aminotransferase activity was measured using two concentrations of isoleucine as amino donor and (1-/sup 14/C)KIV as amino acceptor. The data show that branched chain aminotransferase activity is located exclusively in the mitochondria in rat heart. Metabolism of extramitochondrial branched chain alpha-keto acids was examined using 20 microM (1-/sup 14/C)KIV and alpha-ketoiso(1-/sup 14/C)caproate (KIC). There was rapid uptake and oxidation of labeled branched chain alpha-keto acid, and, regardless of the experimental condition, greater than 90% of the labeled keto acid substrate was metabolized during the 20-min incubation. When a branched chain amino acid (200 microM) or glutamate (5 mM) was present, 30-40% of the labeled keto acid was transaminated while the remainder was oxidized. Provision of an alternate amino acceptor in the form of alpha-keto-glutarate (0.5 mM) decreased transamination of the labeled KIV or KIC and increased oxidation. Metabolism of intramitochondrially generated branched chain alpha-keto acids was studied using (1-/sup 14/C)leucine and (1-/sup 14/C)valine. Essentially all of the labeled branched chain alpha-keto acid produced by transamination of (1-/sup 14/C)leucine or (1-/sup 14/C)valine with a low concentration of unlabeled branched chain alpha-keto acid (20 microM) was oxidized.

  1. Reliable Metabolic Flux Estimation in Escherichia coli Central Carbon Metabolism Using Intracellular Free Amino Acids

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    Nobuyuki Okahashi

    2014-05-01

    Full Text Available 13C metabolic flux analysis (MFA is a tool of metabolic engineering for investigation of in vivo flux distribution. A direct 13C enrichment analysis of intracellular free amino acids (FAAs is expected to reduce time for labeling experiments of the MFA. Measurable FAAs should, however, vary among the MFA experiments since the pool sizes of intracellular free metabolites depend on cellular metabolic conditions. In this study, minimal 13C enrichment data of FAAs was investigated to perform the FAAs-based MFA. An examination of a continuous culture of Escherichia coli using 13C-labeled glucose showed that the time required to reach an isotopically steady state for FAAs is rather faster than that for conventional method using proteinogenic amino acids (PAAs. Considering 95% confidence intervals, it was found that the metabolic flux distribution estimated using FAAs has a similar reliability to that of the PAAs-based method. The comparative analysis identified glutamate, aspartate, alanine and phenylalanine as the common amino acids observed in E. coli under different culture conditions. The results of MFA also demonstrated that the 13C enrichment data of the four amino acids is required for a reliable analysis of the flux distribution.

  2. Patterns of amino acid metabolism by proliferating human mesenchymal stem cells

    NARCIS (Netherlands)

    Higuera, G.A.; Schop, D.; Spitters, T.W.; Dijkhuizen, R.; Bracke, M.; Bruijn, J.D.; Martens, D.E.; Karperien, M.; Boxtel, van A.J.B.; Blitterswijk, van C.A.

    2012-01-01

    The nutritional requirements of stem cells have not been determined; in particular, the amino acid metabolism of stem cells is largely unknown. In this study, we investigated the amino acid metabolism of human mesenchymal stem cells (hMSCs), with focus on two questions: Which amino acids are consume

  3. Defining meal requirements for protein to optimize metabolic roles of amino acids

    Science.gov (United States)

    Dietary protein provides essential amino acids (EAAs) for the synthesis of new proteins plus an array of other metabolic functions; many of these functions are sensitive to postprandial plasma and intracellular amino acid concentrations. Recent research has focused on amino acids as metabolic signal...

  4. Chemical Modification of Amino Acid Residues in Human Plasminogen

    Institute of Scientific and Technical Information of China (English)

    LIANG Fang; SUN Hong; ZHAO Cheng-guang; CUI Ting; HONG Shui-sheng; CHEN Jia; LIU Lan-ying

    2003-01-01

    The chemical modification of human plasminogen(HPg) was studied with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC), N-acetylimidazole(NAI), 1,2-cyclohexanedione(CHD), chloramine T(Ch-T) and N-bromosuccinimide(NBS) as modifying reagents at its carboxyl group, tyrosine, arginine, methionine and tryptophan residues, respectively. The results indicate that tyrosine and arginine residues are not essential for HPg activity, while carboxyl groups, methionine and tryptophan residues are important for the activity of HPg. The Keech and Farrant′s kinetic analysis reveals that one tryptophan residue, one methionine residue and two carboxyl groups are essential for HPg activity.

  5. Chemical modification of amino acids by atmospheric-pressure cold plasma in aqueous solution

    Science.gov (United States)

    Takai, Eisuke; Kitamura, Tsuyoshi; Kuwabara, Junpei; Ikawa, Satoshi; Yoshizawa, Shunsuke; Shiraki, Kentaro; Kawasaki, Hideya; Arakawa, Ryuichi; Kitano, Katsuhisa

    2014-07-01

    Plasma medicine is an attractive new research area, but the principles of plasma modification of biomolecules in aqueous solution remain elusive. In this study, we investigated the chemical effects of atmospheric-pressure cold plasma on 20 naturally occurring amino acids in aqueous solution. High-resolution mass spectrometry revealed that chemical modifications of 14 amino acids were observed after plasma treatment: (i) hydroxylation and nitration of aromatic rings in tyrosine, phenylalanine and tryptophan; (ii) sulfonation and disulfide linkage formation of thiol groups in cysteine; (iii) sulfoxidation of methionine and (iv) amidation and ring-opening of five-membered rings in histidine and proline. A competitive reaction experiment using 20 amino acids demonstrated that sulfur-containing and aromatic amino acids were preferentially decreased by the plasma treatment. These data provide fundamental information for elucidating the mechanism of protein inactivation for biomedical plasma applications.

  6. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    DEFF Research Database (Denmark)

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S;

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pat......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.......Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy...

  7. Dynamics of human whole body amino acid metabolism

    International Nuclear Information System (INIS)

    The mechanism of regulation of the nitrogen metabolism in humans under various nutritional and physiological states was examined using stable isotopes. In the simultaneous continuous infusion of 1- [13] - leucine and α- [15N]- lysine, their fluxed decreased when individuals received lower protein intake. The rates of oxidation and incorporation into body proteins of leucine changed in parallel with the protein intake. Such effects of diet on whole body leucine kinetics were modified by the energy state and dietary energy level. The nitrogen balance was also improved by an excess level of dietary energy. When the intake of dietary protein was lowered below the maintenance level, the whole body flux and de novo synthesis of glycine were lowered, but alanine synthesis was clearly increased. The intravenous infusion of glucose at 4 mg/kg.min, which causes increase in excess blood sugar and plasma insulin, increased the alanine flux, but had no effect on the glycine flux. The rate of albumin synthesis, determined by giving 15N-glycine orally every 3 hr, decreased with the lowered intake of dietary protein in young men, but not in elderly men. This explains why the serum albumin synthesis increases with the increase in the intake of dietary protein in young men, but not in elderly men. The rate of whole body protein synthesis in young men receiving the L-amino acid diets providing with the required intake of specific amino acid was much lower than that in the men receiving the diets providing with generous intake of specific amino acid. Thus the control mechanism to maintain the homeostasis of body nitrogen and amino acids is related in some unknown way to the nutritional requirement of the hosts. (Kaihara, S.)

  8. Amino acid supplementation alters bone metabolism during simulated weightlessness

    Science.gov (United States)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  9. Postsynthetic modification of an amino-tagged MOF using peptide coupling reagents: a comparative study.

    Science.gov (United States)

    Hintz, Henrik; Wuttke, Stefan

    2014-10-01

    The suitability of four peptide coupling reagents for postsynthetic modification (PSM) of amino-tagged metal-organic frameworks (MOFs) with carboxylic acids was investigated. Mild reaction conditions at room temperature allow effective covalent attachment of drugs and biomolecules inside the pores of MOFs with moderate chemical stability.

  10. Modeling the role of covalent enzyme modification in Escherichia coli nitrogen metabolism

    Science.gov (United States)

    Kidd, Philip B.; Wingreen, Ned S.

    2010-03-01

    In the bacterium Escherichia coli, the enzyme glutamine synthetase (GS) converts ammonium into the amino acid glutamine. GS is principally active when the cell is experiencing nitrogen limitation, and its activity is regulated by a bicyclic covalent modification cascade. The advantages of this bicyclic-cascade architecture are poorly understood. We analyze a simple model of the GS cascade in comparison to other regulatory schemes and conclude that the bicyclic cascade is suboptimal for maintaining metabolic homeostasis of the free glutamine pool. Instead, we argue that the lag inherent in the covalent modification of GS slows the response to an ammonium shock and thereby allows GS to transiently detoxify the cell, while maintaining homeostasis over longer times.

  11. Comparison of bare and amino modified mesoporous silica@poly(ethyleneimine)s xerogel as indomethacin carrier: Superiority of amino modification.

    Science.gov (United States)

    Li, Jing; Xu, Lu; Wang, Hongyu; Yang, Baixue; Liu, Hongzhuo; Pan, Weisan; Li, Sanming

    2016-02-01

    The purpose of this study was to facilely develop amino modified mesoporous silica xerogel synthesized using biomimetic method (B-AMSX) and to investigate its potential ability to be a drug carrier for loading poorly water-soluble drug indomethacin (IMC). For comparison, mesoporous silica xerogel without amino modification (B-MSX) was also synthesized using the same method. The changes of characteristics before and after IMC loading were systemically studied using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS) and nitrogen adsorption/desorption analysis. The results showed that B-MSX and B-AMSX were spherical nanoparticles with mesoporous structure. Compared with B-MSX, IMC loading capacity of B-AMSX was higher because more drug molecules can be loaded through stronger hydrogen bonding force. DSC and SAXS analysis confirmed the amorphous state of IMC after being loaded into B-MSX and B-AMSX. The in vitro drug release study revealed that B-MSX and B-AMSX improved IMC release significantly, and B-AMSX released IMC a little faster than B-MSX because of larger pore diameter of IMC-AMSX. B-MSX and B-AMSX degraded gradually in dissolution medium evidenced by color reaction and absorbance value, and B-AMSX degraded slower than B-MSX due to amino modification. In conclusion, B-AMSX with superiority of higher loading capacity and enhanced dissolution release can be considered to be a good candidate as drug carrier for IMC.

  12. Comparison of bare and amino modified mesoporous silica@poly(ethyleneimine)s xerogel as indomethacin carrier: Superiority of amino modification.

    Science.gov (United States)

    Li, Jing; Xu, Lu; Wang, Hongyu; Yang, Baixue; Liu, Hongzhuo; Pan, Weisan; Li, Sanming

    2016-02-01

    The purpose of this study was to facilely develop amino modified mesoporous silica xerogel synthesized using biomimetic method (B-AMSX) and to investigate its potential ability to be a drug carrier for loading poorly water-soluble drug indomethacin (IMC). For comparison, mesoporous silica xerogel without amino modification (B-MSX) was also synthesized using the same method. The changes of characteristics before and after IMC loading were systemically studied using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS) and nitrogen adsorption/desorption analysis. The results showed that B-MSX and B-AMSX were spherical nanoparticles with mesoporous structure. Compared with B-MSX, IMC loading capacity of B-AMSX was higher because more drug molecules can be loaded through stronger hydrogen bonding force. DSC and SAXS analysis confirmed the amorphous state of IMC after being loaded into B-MSX and B-AMSX. The in vitro drug release study revealed that B-MSX and B-AMSX improved IMC release significantly, and B-AMSX released IMC a little faster than B-MSX because of larger pore diameter of IMC-AMSX. B-MSX and B-AMSX degraded gradually in dissolution medium evidenced by color reaction and absorbance value, and B-AMSX degraded slower than B-MSX due to amino modification. In conclusion, B-AMSX with superiority of higher loading capacity and enhanced dissolution release can be considered to be a good candidate as drug carrier for IMC. PMID:26652425

  13. Targeting amino acid metabolism in cancer growth and anti-tumor immune response

    Institute of Scientific and Technical Information of China (English)

    Elitsa; Ananieva

    2015-01-01

    Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.

  14. AMINO ACID METABOLISM IN COWS DURING THE TRANSITION PERIOD IN BALANCING DIET ON THE EXCHANGE PROTEIN AND DIGESTIBLE AMINO ACIDS

    Directory of Open Access Journals (Sweden)

    Ryadchikov V. G.

    2014-02-01

    Full Text Available Application of a factorial method for determining the needs in metabolic protein and essential amino acids, helps to deepen knowledge on physiology of protein and amino acid supply and allow to improve the standards for dairy cows during the transition period; in insufficient of metabolic protein and essential amino acids increased coefficients of their transformation into net protein and absorptive amino acids as a result of mobilization of body of cows; with an optimal protein nutrition their transformation in net milk protein, lysine and methionine accordingly amounted to 0.67, 0,83 and 0,82. The most significant changes in the concentration of methionine, proline, glutamate, glutamine, glycine were observed in cows before calving and immediately after birth, stabilization of their level starts with a 24 lactation day, that is connected with the peculiarities of the feeding behavior of the cows and the gradual intensification of the processes of metabolism and milk production. To control the status of protein metabolism we have offered benchmarks compositions of free amino acids in cows’ blood plasma phases: 21-0 days before calving, 0-21 and 22-120 days after calving

  15. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels.

    Science.gov (United States)

    Smith, M Ryan; Vayalil, Praveen K; Zhou, Fen; Benavides, Gloria A; Beggs, Reena R; Golzarian, Hafez; Nijampatnam, Bhavitavya; Oliver, Patsy G; Smith, Robin A J; Murphy, Michael P; Velu, Sadanandan E; Landar, Aimee

    2016-08-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP), decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231) breast adenocarcinoma cells up to 6 days after an initial 24h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR) in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10µM) of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC) protein levels, although other protein levels were unaffected. This study

  16. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels.

    Science.gov (United States)

    Smith, M Ryan; Vayalil, Praveen K; Zhou, Fen; Benavides, Gloria A; Beggs, Reena R; Golzarian, Hafez; Nijampatnam, Bhavitavya; Oliver, Patsy G; Smith, Robin A J; Murphy, Michael P; Velu, Sadanandan E; Landar, Aimee

    2016-08-01

    Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP), decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231) breast adenocarcinoma cells up to 6 days after an initial 24h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR) in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10µM) of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC) protein levels, although other protein levels were unaffected. This study

  17. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

    Directory of Open Access Journals (Sweden)

    M. Ryan Smith

    2016-08-01

    Full Text Available Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP, decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231 breast adenocarcinoma cells up to 6 days after an initial 24 h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10 µM of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC protein levels, although other protein levels were

  18. Tetrazine-Containing Amino Acid for Peptide Modification and Live Cell Labeling.

    Directory of Open Access Journals (Sweden)

    Zhongqiu Ni

    Full Text Available A novel amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl phenyl-2-aminopropanoic acid was synthesized in this study. The compound possessed better water-solubility and was synthesized more easily compared with the well-known and commercially available 3-(p-benzylamino-1, 2, 4, 5-tetrazine. Tetrazine-containing amino acid showed excellent stability in biological media and might be used for cancer cell labeling. Moreover, the compound remained relatively stable in 50% TFA/DCM with little decomposition after prolonged exposure at room temperature. The compound could be utilized as phenylalanine or tyrosine analogue in peptide modification, and the tetrazine-containing peptide demonstrated more significant biological activity than that of the parent peptide. The combination of tetrazine group and amino acid offered broad development prospects of the bioorthogonal labeling and peptide synthesis.

  19. Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition.

    Science.gov (United States)

    Mitchell, W Kyle; Wilkinson, Daniel J; Phillips, Bethan E; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J

    2016-07-01

    Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle "quality" decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies. PMID:27422520

  20. Effects of amino silicone oil modification on properties of ramie fiber and ramie fiber/polypropylene composites

    International Nuclear Information System (INIS)

    Highlights: • Ramie fiber (RF) changed to be hydrophobic after amino silicone oil modification. • Mechanical properties of RF/PP composites improved after fiber being modified. • N−H=O and O−H=N hydrogen bonds formed at the interface of modifier and fiber. • Amino silicone molecular interacts with cellulose in a preferred orientation. - Abstract: The effects of amino silicone oil modification on the properties of ramie fiber and ramie/polypropylene composites were investigated with experiments and molecular dynamics simulation. First, the effects of amino silicone oil treatments on the properties of ramie and ramie/polypropylene composites were investigated by experiments. The results indicated that the amino silicone oil modification can change the surface properties of ramie fiber from hydrophilic to hydrophobic and improve the mechanical properties of ramie/polypropylene composites. And then, the amino silicone oil modification mechanism at atomic and molecular levels was investigated by the molecular dynamics simulation. The simulation work elucidate that the surface modification mechanism can be described as: the amino silicone oil can interact with cellulose by the intermolecular forces, and the molecular chain of amino silicone oil tends to be an orientation that the hydrophobic alkyl groups project outward and the polar amino groups point to the surface of cellulose. Therefore, the surface of ramie fiber was covered with amino silicone oil, and the surface property of ramie fiber was changed from hydrophilic to hydrophobic. So the surface modification with amino silicone oil can improve the interfacial compatibility between ramie fiber and polymer

  1. Physiological and biochemical studies of bacterial amino acid amide metabolism

    NARCIS (Netherlands)

    Hermes, Hubertus Franciscus Maria

    2008-01-01

    Amino acids represent a class of versatile chiral building blocks for a whole range of fine chemicals, used in the pharmaceutical and agro-chemical industry. Considerable experience currently is available with a wide variety of chemo-enzymatic processes for the synthesis of amino acids, which is app

  2. Nitrogen and amino acid metabolism in dairy cows

    NARCIS (Netherlands)

    Tamminga, S.

    1981-01-01

    For the process of milk production, the dairy cow requires nutrients of which energy supplying nutrients and protein or amino acid supplying nutrients are the most important. Amino acid supplying nutrients have to be absorbed from the small intestine and the research reported in this thesis mainly c

  3. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  4. Microbial transglutaminase production by Streptoverticillium mobaraense: Analysis of amino acid metabolism using mass balances

    NARCIS (Netherlands)

    Zhu, Y.; Rinzema, A.; Bonarius, H.P.J.; Tramper, J.; Bol, J.

    1998-01-01

    Metabolic flows, especially those of amino acids, were determined and analyzed at different stages of a batch fermentation for microbial transglutaminase production by Streptoverticillium mobaraense. The method is mainly based on mass balances and measurements of amino acids and other metabolites. T

  5. Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Directory of Open Access Journals (Sweden)

    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  6. Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis and intermediary metabolism. Metabolic flux in developing maize kernels.

    Science.gov (United States)

    Glawischnig, E; Gierl, A; Tomas, A; Bacher, A; Eisenreich, W

    2001-03-01

    Information on metabolic networks could provide the basis for the design of targets for metabolic engineering. To study metabolic flux in cereals, developing maize (Zea mays) kernels were grown in sterile culture on medium containing [U-(13)C(6)]glucose or [1,2-(13)C(2)]acetate. After growth, amino acids, lipids, and sitosterol were isolated from kernels as well as from the cobs, and their (13)C isotopomer compositions were determined by quantitative nuclear magnetic resonance spectroscopy. The highly specific labeling patterns were used to analyze the metabolic pathways leading to amino acids and the triterpene on a quantitative basis. The data show that serine is generated from phosphoglycerate, as well as from glycine. Lysine is formed entirely via the diaminopimelate pathway and sitosterol is synthesized entirely via the mevalonate route. The labeling data of amino acids and sitosterol were used to reconstruct the labeling patterns of key metabolic intermediates (e.g. acetyl-coenzyme A, pyruvate, phosphoenolpyruvate, erythrose 4-phosphate, and Rib 5-phosphate) that revealed quantitative information about carbon flux in the intermediary metabolism of developing maize kernels. Exogenous acetate served as an efficient precursor of sitosterol, as well as of amino acids of the aspartate and glutamate family; in comparison, metabolites formed in the plastidic compartments showed low acetate incorporation. PMID:11244098

  7. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  8. Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Saltin, B; Wagenmakers, A J

    1999-01-01

    acid production was also 10-fold higher during exercise compared with that at rest (difference not significant). The net production rates of threonine, glycine and tyrosine and of the sum of the non-metabolized amino acids were about 1.5-2.5-fold higher during exercise with the leg with a low glycogen...... in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60......-65% of maximal one-leg power output, starting either with the normal-glycogen or the low-glycogen leg, at random. The net production of threonine, lysine and tyrosine and the sum of the non-metabolized amino acids were 9-20-fold higher (Prest. Total amino...

  9. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

    Directory of Open Access Journals (Sweden)

    Luigi Fontana

    2016-07-01

    Full Text Available Protein-restricted (PR, high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

  10. Metabolic regulation of amino acid uptake in marine waters

    Energy Technology Data Exchange (ETDEWEB)

    Kirchman, D.L.; Hodson, R.E.

    1986-03-01

    To determine the relationships among the processes of uptake, intracellular pool formation, and incorporation of amino acids into protein, the authors measured the uptake of dipeptides and free amino acids by bacterial assemblages in estuarine and coastal waters of the southeast US. The dipeptide phenylalanyl-phenylalanine (phe-phe) lowered V/sub max/ of phenylalanine uptake when the turnover rate of phenylalanine was relatively high. When the turnover rate was relatively low, phe-phe either had no effect or increased V/sub max/ of phenylalanine uptake. An analytical model was developed and tested to measure the turnover time of the intracellular pool of phenylalanine. The results suggested that the size of the intracellular pool is regulated, which precludes high assimilation rates of both phenylalanine and phe-phe. In waters with relatively low phenylalanine turnover rates, bacterial assemblages appear to have a greater capacity to assimilate phenylalanine and phe-phe simultaneously. Marine bacterial assemblages do not substantially increase the apparent respiration of amino acids when concentrations increase. The authors conclude that sustained increases in uptake rates and mineralization by marine bacterial assemblages in response to an increase in the concentrations of dissolved organic nitrogen is determined by the rate of protein synthesis.

  11. Branched chain amino acids requirements and metabolism in pigs

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham

    2015-01-01

    reasons: first, BCAA share the same enzymes in their catabolic pathways, and there is an interaction among them in a way that excess Leu for example increases the catabolism of them all and changes the requirements. Second, BCAA are not only building blocks of protein biosynthesis, but are also involved......, and Leu requirements in ratio to Lys for pigs after weaning and second, to study the metabolic profile in blood and urine of pigs fed with different BCAA in the diet, and finally, to identify the biomarkers of BCAA, when pigs were fed with the optimum dietary BCAA level to support the best growth...... of the last “-omics”, is a global analysis and interpretation of metabolome in specific health or nutritional status. Non-targeted metabolomics is used for screening the metabolic profile, and the metabolic signature could be used for hypothesis generation. The results of a non-targeted LC-MS metabolomics...

  12. Amino acid adsorption on mesoporous materials: influence of types of amino acids, modification of mesoporous materials, and solution conditions.

    Science.gov (United States)

    Gao, Qiang; Xu, Wujun; Xu, Yao; Wu, Dong; Sun, Yuhan; Deng, Feng; Shen, Wanling

    2008-02-21

    In order to disclose the dominant interfacial interaction between amino acids and ordered mesoporous materials, the adsorption behaviors of five amino acids on four mesoporous materials were investigated in aqueous solutions with adjustable amino acid concentration, ion strength, and pH. The selected amino acids were acidic amino acid glutamic acid (Glu), basic amino acid arginine (Arg), and neutral amino acids phenylalanine (Phe), leucine (Leu), and alanine (Ala), and the selected mesoporous materials were SBA-15, Al-SBA-15, CH3(10%)-SBA-15, and CH3(20%)-SBA-15. The adsorption capacities of Glu and Arg were strongly dependent on pH and surface charge of the mesoporous adsorbent. The adsorption of Phe showed pH insensitivity but depended on the surface organic functionalization of mesoporous adsorbent. On the basis of the theoretical analysis about the interaction between amino acid and adsorbent, such a remarkable difference was attributed to the different nature of the interaction between amino acid and adsorbent. Arg could be readily adsorbed on the surface of SBA-15, especially Al-SBA-15, under appropriate pH in which the electrostatic interaction was predominant. The driving force of Phe adsorption on mesoporous adsorbent mainly came from the hydrophobic interaction. Therefore, the adsorption capability of Arg decreased with increasing ion strength of solution, while the adsorption capability of Phe increased with the increasing degree of CH3 functionalization on SBA-15. For neutral amino acid Phe, Ala, and Leu, the adsorption capability increased with the increase of the length of their side chains, which was another evidence of hydrophobic effect. Thus, all the adsorption of amino acids on mesoporous silica materials can be decided by the combined influence of two fundamental interactions: electrostatic attraction and hydrophobic effect.

  13. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery

    DEFF Research Database (Denmark)

    Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin;

    2015-01-01

    (acylcarnitines) and lipolysis (glycerol) did not indicate impaired metabolic flexibility during exercise in diabetic participants. CONCLUSIONS/INTERPRETATION: Type 2 diabetic individuals showed specific exercise-regulated gene expression. These data provide novel insight into potential mechanisms to ameliorate......AIMS/HYPOTHESIS: The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite...... showed an exercise-induced compensatory regulation of genes involved in biosynthesis and metabolism of amino acids (PSPH, GATM, NOS1 and GLDC), which responded to differences in the amino acid profile (consistently lower plasma levels of glycine, cysteine and arginine). Markers of fat oxidation...

  14. Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria

    Institute of Scientific and Technical Information of China (English)

    Purnima Guda; Chittibabu Guda; Shankar Subramaniam

    2007-01-01

    We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochon- dria. Human mitochondrial proteins determined by experimental and computa- tional methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mito- chondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which pre- dicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we recon- structed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.

  15. TREATMENT OF THE METABOLIC SYNDROME: THE IMPACT OF LIFESTYLE MODIFICATION

    Science.gov (United States)

    Along with the increasing prevalence of obesity comes a constellation of metabolic derangements: dyslipidemias, hypertension, insulin resistance, and glucose intolerance, as well as increased prothrombotic and inflammatory markers. The association of these factors has been termed the "metabolic synd...

  16. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Directory of Open Access Journals (Sweden)

    Roze Ludmila V

    2010-08-01

    Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

  17. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Science.gov (United States)

    2010-01-01

    Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary

  18. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Knudsen, Karen Birgitte Moos; Kondrup, Jens;

    2001-01-01

    BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine...

  19. Comparative functional genomics of amino acid metabolism of lactic acid bacteria

    NARCIS (Netherlands)

    Pastink, M.I.

    2009-01-01

    The amino acid metabolism of lactic acid bacteria used as starters in industrial fermentations has profound effects on the quality of the fermented foods. The work described in this PhD thesis was initiated to use genomics technologies and a comparative approach to link the gene content of some well

  20. Change of oxygen free radical metabolism and free amino acids of patients with hyperthyroidism

    Institute of Scientific and Technical Information of China (English)

    Hua-Ling Ruan; Li Zhao; Kun-Quan Guo; Kun Yang; Lin-Xiu Ye; Xue Sun

    2016-01-01

    Objective:To study the change situation of oxygen free radical metabolism and free amino acids of patients with hyperthyroidism.Methods:Eighty-one patients with hyperthyroidism who were treated in our hospital from May 2013 to October 2014 were selected as the observation group, while 81 healthy persons with health examination at the same period were the control group. Then, the serum oxygen free radical indexes and free amino acids of the two groups were respectively detected and compared, and the detection results of patients in the observation group with different etiologic types and basal metabolic rate were also compared. Results:The serum oxygen free radical related indexes of the observation group were all higher than those of the control group; the serum antioxidant related indexes were all lower than those of the control group; and the serum free amino acids levels were all obviously lower than those of the control group. Besides, the detection results of patients with severe hyperthyroidism in the observation group were worse than those of patients with mild and moderate disease, while the detection results of the observation group with different types of hyperthyroidism had no significant differences.Conclusions:The fluctuation of oxygen free radical metabolism and free amino acids of patients with hyperthyroidism are obvious, and the detection results of patients with different basal metabolic rates are also quite obvious.

  1. New insights into the regulation of plant immunity by amino acid metabolic pathways.

    Science.gov (United States)

    Zeier, Jürgen

    2013-12-01

    Besides defence pathways regulated by classical stress hormones, distinct amino acid metabolic pathways constitute integral parts of the plant immune system. Mutations in several genes involved in Asp-derived amino acid biosynthetic pathways can have profound impact on plant resistance to specific pathogen types. For instance, amino acid imbalances associated with homoserine or threonine accumulation elevate plant immunity to oomycete pathogens but not to pathogenic fungi or bacteria. The catabolism of Lys produces the immune signal pipecolic acid (Pip), a cyclic, non-protein amino acid. Pip amplifies plant defence responses and acts as a critical regulator of plant systemic acquired resistance, defence priming and local resistance to bacterial pathogens. Asp-derived pyridine nucleotides influence both pre- and post-invasion immunity, and the catabolism of branched chain amino acids appears to affect plant resistance to distinct pathogen classes by modulating crosstalk of salicylic acid- and jasmonic acid-regulated defence pathways. It also emerges that, besides polyamine oxidation and NADPH oxidase, Pro metabolism is involved in the oxidative burst and the hypersensitive response associated with avirulent pathogen recognition. Moreover, the acylation of amino acids can control plant resistance to pathogens and pests by the formation of protective plant metabolites or by the modulation of plant hormone activity.

  2. Two food-borne heterocyclic amines: Metabolism and DNA adduct formation of amino-alpha-carbolines

    DEFF Research Database (Denmark)

    Frederiksen, Hanne

    2005-01-01

    or proteins of animal or vegetable origin, furthermore they are found in many cooked foods, such as fish, meat, and chicken. The specific mutagenicity of the amino-a-carbolines are lower in the Ames Salmonella assay than other heterocyclic amines, but in rodent studies the carcinogenicity of the aminoa, alpha...... been studied. Characteristic for the amino-a-carbolines are that relatively large amounts of these compounds in rat and human hepatic microsomes are activated to potent carcinogenic compounds compared with other heterocyclic amines, but further in vivo studies of the amino-a-carbolines are needed...... to highlight these indications. In this review, the main characteristics with focus on the metabolism and the DNA-adduct formation of the amino-a-carbolines are described and compared with other heterocyclic amines....

  3. From start to finish: amino-terminal protein modifications as degradation signals in plants.

    Science.gov (United States)

    Gibbs, Daniel J; Bailey, Mark; Tedds, Hannah M; Holdsworth, Michael J

    2016-09-01

    Contents 1188 I. 1188 II. 1189 III. 1190 IV. 1191 V. 1192 1192 References 1192 SUMMARY: The amino- (N-) terminus (Nt) of a protein can undergo a diverse array of co- and posttranslational modifications. Many of these create degradation signals (N-degrons) that mediate protein destruction via the N-end rule pathway of ubiquitin-mediated proteolysis. In plants, the N-end rule pathway has emerged as a major system for regulated control of protein stability. Nt-arginylation-dependent degradation regulates multiple growth, development and stress responses, and recently identified functions of Nt-acetylation can also be linked to effects on the in vivo half-lives of Nt-acetylated proteins. There is also increasing evidence that N-termini could act as important protein stability determinants in plastids. Here we review recent advances in our understanding of the relationship between the nature of protein N-termini, Nt-processing events and proteolysis in plants. PMID:27439310

  4. Chemical modification of an alpha 3-fucosyltransferase; definition of amino acid residues essential for enzyme activity.

    Science.gov (United States)

    Britten, C J; Bird, M I

    1997-02-11

    The biosynthesis of the carbohydrate antigen sialyl Lewis X (sLe(x)) is dependent on the activity of an alpha 3-fucosyltransferase (EC 2.4.1.152, GDP-fucose:Gal beta (1-4)GlcNAc-R alpha (1-3)fucosyltransferase). This enzyme catalyses the transfer of fucose from GDP-beta-fucose to the 3-OH of N-acetylglucosamine present in lactosamine acceptors. In this report, we have investigated the amino acids essential for the activity of a recombinant alpha 3-fucosyltransferase (FucT-VI) through chemical modification of the enzyme with group-selective reagents. FucT-VI activity was found to be particularly sensitive to the histidine-selective reagent diethylpyrocarbonate and the cysteine reagent N-ethylmaleimide, with IC50 values of less than 200 microM. Reagents selective for arginine and lysine had no effect on enzyme activity. The inclusion of GDP-beta-fucose during preincubation with NEM reduces the rate of inactivation whereas inclusion of an acceptor saccharide for the enzyme, Gal beta (1-4)GlcNAc, had no effect. No protective effect with either GDP-beta-fucose or Gal beta (1-4)GlcNAc was observed on treatment of the enzyme with diethylpyrocarbonate. These data suggest that in addition to an NEM-reactive cysteine in, or adjacent to, the substrate-binding site of the enzyme, FucT-VI possesses histidine residue(s) that are essential for enzyme activity.

  5. Metabolic switch during adipogenesis: From branched chain amino acid catabolism to lipid synthesis.

    Science.gov (United States)

    Halama, Anna; Horsch, Marion; Kastenmüller, Gabriele; Möller, Gabriele; Kumar, Pankaj; Prehn, Cornelia; Laumen, Helmut; Hauner, Hans; Hrabĕ de Angelis, Martin; Beckers, Johannes; Suhre, Karsten; Adamski, Jerzy

    2016-01-01

    Fat cell metabolism has an impact on body homeostasis and its proper function. Nevertheless, the knowledge about simultaneous metabolic processes, which occur during adipogenesis and in mature adipocytes, is limited. Identification of key metabolic events associated with fat cell metabolism could be beneficial in the field of novel drug development, drug repurposing, as well as for the discovery of patterns predicting obesity risk. The main objective of our work was to provide comprehensive characterization of metabolic processes occurring during adipogenesis and in mature adipocytes. In order to globally determine crucial metabolic pathways involved in fat cell metabolism, metabolomics and transcriptomics approaches were applied. We observed significantly regulated metabolites correlating with significantly regulated genes at different stages of adipogenesis. We identified the synthesis of phosphatidylcholines, the metabolism of even and odd chain fatty acids, as well as the catabolism of branched chain amino acids (BCAA; leucine, isoleucine and valine) as key regulated pathways. Our further analysis led to identification of an enzymatic switch comprising the enzymes Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase) and Auh (AU RNA binding protein/enoyl-CoA hydratase) which connects leucine degradation with cholesterol synthesis. In addition, propionyl-CoA, a product of isoleucine degradation, was identified as a putative substrate for odd chain fatty acid synthesis. The uncovered crosstalks between BCAA and lipid metabolism during adipogenesis might contribute to the understanding of molecular mechanisms of obesity and have potential implications in obesity prediction. PMID:26408941

  6. Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-08-01

    Full Text Available Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

  7. Metabolism of Aromatic Amino Acids during the Growth Cycle of Batch Suspension Cultures of Catharanthus roseus

    OpenAIRE

    Nagaoka, Noriko; ASHIHARA, Hiroshi

    1988-01-01

    Profiles of the levels and metabolism of aromatic compounds in suspension-cultured cells of Catharanthus roseus during the growth cycle were determined. The level of total protein-amino acids, i.e., sum of the amounts of amino acids in hydrolyzates of proteins, and the level of total phenolic acids increased after transfer of the cells in the stationary phase to fresh Murashige-Skoog medium. The maximum levels of the proteinamino acids and those of the phenolic acids were observed on days 3-5...

  8. Lifestyle modification in the management of the metabolic syndrome: achievements and challenges

    Directory of Open Access Journals (Sweden)

    Riccardo Dalle Grave

    2010-11-01

    Full Text Available Riccardo Dalle Grave1, Simona Calugi1, Elena Centis2, Rebecca Marzocchi2, Marwan El Ghoch1, Giulio Marchesini21Department of Eating & Weight Disorder, Villa Garda Hospital, Garda (VR, Italy; 2Unit of Metabolic Diseases & Clinical Dietetics, Alma Mater Studiorum – University of Bologna, Bologna, ItalyAbstract: Lifestyle modification based on behavior therapy is the most important and effective strategy to manage the metabolic syndrome. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioral and cognitive strategies. The intervention may be delivered face-to-face or in groups, or in groups combined with individual sessions. The main challenge of treatment is helping patients maintain healthy behavior changes in the long term. In the last few years, several strategies have been evaluated to improve the long-term effect of lifestyle modification. Promising results have been achieved by combining lifestyle modification with pharmacotherapy, using meals replacement, setting higher physical activity goals, and long-term care. The key role of cognitive processes in the success/failure of weight loss and maintenance suggests that new cognitive procedures and strategies should be included in the traditional lifestyle modification interventions, in order to help patients build a mind-set favoring long-term lifestyle changes. These new strategies raise optimistic expectations for an effective treatment of metabolic syndrome with lifestyle modifications, provided public health programs to change the environment where patients live support them.Keywords: metabolic syndrome, obesity, lifestyle modification, cognitive behavior therapy

  9. Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

    DEFF Research Database (Denmark)

    Mourtzakis, Marina; Saltin, B.; Graham, T.;

    2006-01-01

    with pyruvate metabolism, and they comprised 68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism......During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline...... at 3 h 23 min ± 11 min). Femoral arterial and venous blood, blood flow measurements, and muscle samples were obtained hourly during exercise and recovery (3 h). Carbohydrate oxidation peaked at 30 min of exercise and subsequently decreased for the remainder of the exercise bout (P

  10. Essential amino acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    Traditional methods used to evaluate protein metabolism left unanswered some of the relevant questions in public health in developing countries, such as growth retardation in children. Particularly, in developing countries, infection (clinical and subclinical) and malnutrition are still relevant problems, and the most important scientific issues for the application of stable isotope tracer methods are related to the impact of infection, such as the oxidative disposal of essential amino acids in well-nourished and malnourished children. The objectives of the present proposal are: (1) To simplify, make less expensive, less time-consuming, and less invasive, methods in clinical research on amino acid metabolism using stable-isotope tracers in children; and (2) To assess the effects of infection (clinical or subclinical) on whole-body protein turnover in children with and without malnutrition. The objectives involve the engineering and assessment of a portable instrument to be used in evaluations of protein oxidation in the developing world. Methodological issues such as intra- and inter-subject variability, which are of great importance for the interpretation of amino acid metabolism and protein turnover, will also be considered. 18 refs, 2 figs

  11. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  12. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    DEFF Research Database (Denmark)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner;

    2016-01-01

    OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. METHODS: To identify pathways related t...... catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D....... methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. RESULTS: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate...... fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. CONCLUSIONS: Our data indicate that impaired muscle BCAA...

  13. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers.

    Science.gov (United States)

    Mayers, Jared R; Torrence, Margaret E; Danai, Laura V; Papagiannakopoulos, Thales; Davidson, Shawn M; Bauer, Matthew R; Lau, Allison N; Ji, Brian W; Dixit, Purushottam D; Hosios, Aaron M; Muir, Alexander; Chin, Christopher R; Freinkman, Elizaveta; Jacks, Tyler; Wolpin, Brian M; Vitkup, Dennis; Vander Heiden, Matthew G

    2016-09-01

    Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements. PMID:27609895

  14. Characteristic metabolism of free amino acids in cetacean plasma: cluster analysis and comparison with mice.

    Directory of Open Access Journals (Sweden)

    Kazuki Miyaji

    Full Text Available From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaptation used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future.

  15. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

    Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were...... incremental increase in hepatic glucose release rather than hepatic catabolism of amino acids....

  16. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue.

    Science.gov (United States)

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males' subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  17. Lysine acetylation is a common post-translational modification of key metabolic pathway enzymes of the anaerobe Porphyromonas gingivalis.

    Science.gov (United States)

    Butler, Catherine A; Veith, Paul D; Nieto, Matthew F; Dashper, Stuart G; Reynolds, Eric C

    2015-10-14

    Porphyromonas gingivalis is a Gram-negative anaerobe considered to be a keystone pathogen in the development of the bacterial-associated inflammatory oral disease chronic periodontitis. Although post-translational modifications (PTMs) of proteins are commonly found to modify protein function in eukaryotes and prokaryotes, PTMs such as lysine acetylation have not been examined in P. gingivalis. Lysine acetylation is the addition of an acetyl group to a lysine which removes this amino acid's positive charge and can induce changes in a protein's secondary structure and reactivity. A proteomics based approach combining immune-affinity enrichment with high sensitivity Orbitrap mass spectrometry identified 130 lysine acetylated peptides from 92 P. gingivalis proteins. The majority of these peptides (71) were attributed to 45 proteins with predicted metabolic activity; these proteins could be mapped to several P. gingivalis metabolic pathways where enzymes catalysing sequential reactions within the same pathway were often found acetylated. In particular, the catabolic pathways of complex anaerobic fermentation of amino acids to produce energy had 12 enzymes lysine acetylated. The results suggest that lysine acetylation may be an important mechanism in metabolic regulation in P. gingivalis, which is vital for P. gingivalis survival and adaptation of its metabolism throughout infection. Statement of significance. Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis, an inflammatory disease of the supporting tissues of the teeth. The ability of the pathogen to induce dysbiosis and disease is related to an array of specific virulence factors and metabolic regulation that enables the bacterium to proliferate in an inflamed periodontal pocket. The mechanisms P. gingivalis uses to adapt to a changing and hostile environment are poorly understood and here we show, for the first time, that enzymes of critical metabolic pathways for energy

  18. Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

    Directory of Open Access Journals (Sweden)

    Pelletier Eric

    2010-10-01

    Full Text Available Abstract Background Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed. Results C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms. Conclusions Analysis of the C

  19. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Yukino Hatazawa

    Full Text Available Peroxisome proliferator-activated receptor (PPAR γ coactivator 1α (PGC-1α is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT 2, branched-chain α-keto acid dehydrogenase (BCKDH, which catabolize BCAA. The expression of BCKDH kinase (BCKDK, which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  20. Modification of amino acids at shock pressures of 3 to 30 GPA: Initial results

    Science.gov (United States)

    Peterson, Etta; Horz, Friedrich; Haynes, Gerald; See, Thomas

    1991-01-01

    Since the discovery of amino acids in the Murchison meteorite, much speculation has focused on their origin and subsequent alteration, including the possible role of secondary processes, both terrestrial and extraterrestrial. As collisional processes and associated shock waves seem to have affected the silicate portions of many primitive meteorites, a mixture of powdered Allende (125-150 m grain size) and nine synthetic amino acids (six protein and three nonprotein) were subjected to controlled shock pressures from 3 to 30 GPa to determine the effect of shocks on amino acid survivability. Preliminary characterizations of the recovered shock products are presented.

  1. Amino acid metabolism in the kidneys of genetic and nutritionally obese rats.

    Science.gov (United States)

    Herrero, M C; Remesar, X; Bladé, C; Arola, L

    1997-06-01

    The ability of the kidney to take up and/or release amino acids has been determined in two models of obesity in Zucker rats, one genetic and the other nutritional (diet-obese). There was a noticeable increase in gluconeogenic amino acids in the arterial blood of diet-obese animals whereas the genetically obese rats showed small variations in the levels of these amino acids. There were significant decreases in renal Gly and Ser, only in the genetically obese rats. Genetically obese animals showed an increase in Glutamine synthetase activity. The uptake and/or release of amino acids showed important variations between the groups. The diet-obese group exhibited greater variation, since this group took up Glu, Ala, Gy, Phe and Citrulline and released Gln, Ser, Arg and Tyr. Genetically obese rats took up Gln, His and Taurine and released Ser. These different patterns may be related to variations in the whole body metabolic rate, since the diet-obese group was more active than the genetically obese group.

  2. Water metabolism and modification of tritium excretion in the rat

    International Nuclear Information System (INIS)

    1. The intake and excretion of tritium were studied in rats exposed to tritiated water vapor. The metabolism of tritium was also investigated in rats given single administrations of tritiated water and in rats given daily administrations (per os or i.p.). The results were essentially in accord with those reported previously. 2. Amounts of drinking water consumed and urine excreted by rats drinking water with 0.15% saccharin were 1.5 to 2 times higher than in rats drinking tap water. The tritium activity in various tissues of rats drinking water with 0.15% saccharin decreased to about half of that of rats drinking tap water. A similar tendency was observed also in rats drinking beer. The diuretic agent sodium acetazolamide also enhanced the urinary excretion of tritium. (author)

  3. Trehalose 6-phosphate coordinates organic and amino acid metabolism with carbon availability.

    Science.gov (United States)

    Figueroa, Carlos M; Feil, Regina; Ishihara, Hirofumi; Watanabe, Mutsumi; Kölling, Katharina; Krause, Ursula; Höhne, Melanie; Encke, Beatrice; Plaxton, William C; Zeeman, Samuel C; Li, Zhi; Schulze, Waltraud X; Hoefgen, Rainer; Stitt, Mark; Lunn, John E

    2016-02-01

    Trehalose 6-phosphate (Tre6P) is an essential signal metabolite in plants, linking growth and development to carbon metabolism. The sucrose-Tre6P nexus model postulates that Tre6P acts as both a signal and negative feedback regulator of sucrose levels. To test this model, short-term metabolic responses to induced increases in Tre6P levels were investigated in Arabidopsis thaliana plants expressing the Escherichia coli Tre6P synthase gene (otsA) under the control of an ethanol-inducible promoter. Increased Tre6P levels led to a transient decrease in sucrose content, post-translational activation of nitrate reductase and phosphoenolpyruvate carboxylase, and increased levels of organic and amino acids. Radio-isotope ((14)CO2) and stable isotope ((13)CO2) labelling experiments showed no change in the rates of photoassimilate export in plants with elevated Tre6P, but increased labelling of organic acids. We conclude that high Tre6P levels decrease sucrose levels by stimulating nitrate assimilation and anaplerotic synthesis of organic acids, thereby diverting photoassimilates away from sucrose to generate carbon skeletons and fixed nitrogen for amino acid synthesis. These results are consistent with the sucrose-Tre6P nexus model, and implicate Tre6P in coordinating carbon and nitrogen metabolism in plants. PMID:26714615

  4. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Science.gov (United States)

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling. PMID:26020623

  5. Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats

    Science.gov (United States)

    Jaspers, Stephen R.; Henriksen, Erik; Jacob, Stephan; Tischler, Marc E.

    1989-01-01

    The effects of muscle unloading, adrenalectomy, and cortisol treatment on the metabolism of branched-chain amino acids in the soleus and extensor digitorum longus of tail-cast suspended rats were investigated using C-14-labeled lucine, isoleucine, and valine in incubation studies. It was found that, compared to not suspended controls, the degradation of branched-chain amino acids in hind limb muscles was accelerated in tail-cast suspended rats. Adrenalectomy was found to abolish the aminotransferase flux and to diminish the dehydrogenase flux in the soleus. The data also suggest that cortisol treatment increases the rate of metabolism of branched-chain amino acids at the dehydrogenase step.

  6. Clinical aggressiveness of malignant gliomas is linked to augmented metabolism of amino acids.

    Science.gov (United States)

    Panosyan, Eduard H; Lasky, Joseph L; Lin, Henry J; Lai, Albert; Hai, Yang; Guo, Xiuqing; Quinn, Michael; Nelson, Stanley F; Cloughesy, Timothy F; Nghiemphu, P Leia

    2016-05-01

    Glutamine, glutamate, asparagine, and aspartate are involved in an enzyme-network that controls nitrogen metabolism. Branched-chain-amino-acid aminotransferase-1 (BCAT1) promotes proliferation of gliomas with wild-type IDH1 and is closely connected to the network. We hypothesized that metabolism of asparagine, glutamine, and branched-chain-amino-acids is associated with progression of malignant gliomas. Gene expression for asparagine synthetase (ASNS), glutaminase (GLS), and BCAT1 were analyzed in 164 gliomas from 156 patients [33-anaplastic gliomas (AG) and 131-glioblastomas (GBM), 64 of which were recurrent GBMs]. ASNS and GLS were twofold higher in GBMs versus AGs. BCAT1 was also higher in GBMs. ASNS expression was twofold higher in recurrent versus new GBMs. Five patients had serial samples: 4-showed higher ASNS and 3-higher GLS at recurrence. We analyzed grade and treatment in 4 groups: (1) low ASNS, GLS, and BCAT1 (n = 96); (2) low ASNS and GLS, but high BCAT1 (n = 26); (3) high ASNS or GLS, but low BCAT1 (n = 25); and (4) high ASNS or GLS and high BCAT1 (n = 17). Ninety-one  % of patients (29/32) with grade-III lesions were in group 1. In contrast, 95 % of patients (62/65) in groups 2-4 had GBMs. Treatment was similar in 4 groups (radiotherapy-80 %; temozolomide-30 %; other chemotherapy-50 %). High expression of ASNS, GLS, and BCAT1 were each associated with poor survival in the entire group. The combination of lower ASNS, GLS, and BCAT1 levels correlated with better survival for newly diagnosed GBMs (66 patients; P = 0.0039). Only tumors with lower enzymes showed improved outcome with temozolomide. IDH1(WT) gliomas had higher expression of these genes. Manipulation of amino acid metabolism in malignant gliomas may be further studied for therapeutics development. PMID:26922345

  7. Amino acid metabolism during total parenteral nutrition in healthy volunteers: evaluation of a new amino acid solution.

    Science.gov (United States)

    Berard, M P; Hankard, R; Cynober, L

    2001-10-01

    The aim of this study was to determine the metabolism and the tolerance of a new amino acid (AA) solution administered under conditions mimicking cyclical parenteral nutrition (PN) in humans. Eight healthy volunteers received peripheral PN for 10 h providing 10.5 mg N x kg(-1) x h(-1) and 2.0 kcal x kg(-1) x h(-1) (glucose-to-lipids ratio: 70/30%). For adaptation, a non-protein energy intake was increased progressively for 90 min; thereafter, AA infusion was started and maintained at a constant rate for 10 h. Plasma and urine concentrations of all the AAs were measured before, during and after the PN. For each given AA, the relation between plasma variations at the steady-state and infusion rate, plasma clearance (Cl), renal clearance (Clr), re-absorption rate (Reab) and, retention rate (Reten) were determined. The nitrogen balance (DeltaN) was calculated during the PN period. The results are presented as means+/-sem. All plasma AA concentrations decreased during the starting period of non-protein energy intake. The plasma AA concentrations reached a steady-state within 3 h upon AA infusion, except for glycine and lysine (6 h). At the steady state, the plasma concentrations of the infused AAs were closely correlated to their infusion rate (y= -18.3+1.5x, r(2)=0.92). The plasma glutamine concentration was maintained during the PN, which indicates that the solution might stimulate the de novo synthesis of this AA. When the PN was stopped, plasma levels of the AAs decreased, most of them returning to their basal levels, or significantly below for lysine (Por= 99%, Reten >or=99% and for non-essential AAs: Cl or= 98% except glycine (95+/-1), aspartate (94+/-2) and histidine (94+/-1), Reten >or=97% except histidine (94+/-1), glycine (95+/-3). These results indicate that in healthy subjects, the amounts of AAs provided by the new solution were well balanced for an intravenous administration, and so were well utilized without excessive urinary excretion. The present study

  8. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Directory of Open Access Journals (Sweden)

    Albert Mas

    2014-01-01

    Full Text Available Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements.

  9. Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

    Science.gov (United States)

    Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao

    2016-01-01

    This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697

  10. Bioactive Compounds Derived from the Yeast Metabolism of Aromatic Amino Acids during Alcoholic Fermentation

    Science.gov (United States)

    Guillamon, Jose Manuel; Torija, Maria Jesus; Beltran, Gemma; Troncoso, Ana M.; Garcia-Parrilla, M. Carmen

    2014-01-01

    Metabolites resulting from nitrogen metabolism in yeast are currently found in some fermented beverages such as wine and beer. Their study has recently attracted the attention of researchers. Some metabolites derived from aromatic amino acids are bioactive compounds that can behave as hormones or even mimic their role in humans and may also act as regulators in yeast. Although the metabolic pathways for their formation are well known, the physiological significance is still far from being understood. The understanding of this relevance will be a key element in managing the production of these compounds under controlled conditions, to offer fermented food with specific enrichment in these compounds or even to use the yeast as nutritional complements. PMID:24895623

  11. Essential amino-acid metabolism in infected/non-infected, poor, Guatemalan children

    International Nuclear Information System (INIS)

    As mentioned above, it was our intention to develop and test a simplified version of the protocol to assess amino acid metabolism in children. With the combined efforts of a team of experts in the field, a generic protocol was developed as a mandate of the first CRP held at Boston in the fall of 1993. During the beginning of 1994, the final version of such a protocol was released to all the participants of the CRP meeting and arrangements were made in order to apply it and assess its usefulness in the field setting. Therefore, we have shifted our activities to apply, assess and adapt the generic protocol. We are now testing the protocol in the field to establish the variability parameters in both between and within individuals. After testing and refining the protocol, with the help of other groups in developed countries, by validation and/or comparative studies, we would be in a better position to recommend it as a tool to study amino acid metabolism in children in developing countries, whether to describe some specific profiles or to evaluate nutrition interventions. 1 fig., 3 tabs

  12. Amino acid metabolism in the human fetus at term: leucine, valine, and methionine kinetics.

    Science.gov (United States)

    van den Akker, Chris H P; Schierbeek, Henk; Minderman, Gardi; Vermes, Andras; Schoonderwaldt, Ernst M; Duvekot, Johannes J; Steegers, Eric A P; van Goudoever, Johannes B

    2011-12-01

    Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.

  13. Targeted modification of storage protein content resulting in improved amino acid composition of barley grain

    DEFF Research Database (Denmark)

    Sikdar, Md. Shafiqul Islam; Bowra, S; Schmidt, Daiana;

    2016-01-01

    C-hordein in barley and ω-gliadins in wheat are members of the prolamins protein families. Prolamins are the major component of cereal storage proteins and composed of non-essential amino acids (AA) such as proline and glutamine therefore have low nutritional value. Using double stranded RNAi sil...

  14. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  15. Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

    International Nuclear Information System (INIS)

    Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VIIa, participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VIIa molecule, namely, 10 γ-carboxylated, N-terminally located glutamic acid residues, 1 β-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VIIa as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VIIa. By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradation, the protein backbone of recombinant factor VIIa was found to be identical with human factor VIIa. Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VIIa. In the recombinant factor VIIa, asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VIIa and human plasma factor VIIa. These results show that factor VIIa as produced in the transfected baby hamster kidney cells is very similar to human plasma factor VIIa and that this cell line thus might represent an alternative source for human factor VIIa

  16. Influence of Amino Acid Metabolism on Embryonic Stem Cell Function and Differentiation.

    Science.gov (United States)

    Kilberg, Michael S; Terada, Naohiro; Shan, Jixiu

    2016-07-01

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have promise in regenerative medicine because of their ability to differentiate into all 3 primary germ layers. This review describes recent advances in the understanding of the link between the metabolism of ESCs/iPSCs and their maintenance/differentiation in the cell culture setting, with particular emphasis on amino acid (AA) metabolism. ESCs are endowed with unique metabolic features with regard to energy consumption, metabolite flux through particular pathways, and macromolecular synthesis. Therefore, nutrient availability has a strong influence on stem cell growth, self-renewal, and lineage specification, both in vivo and in vitro. Evidence from several laboratories has documented that self-renewal and differentiation of mouse ESCs are critically dependent on proline metabolism, with downstream metabolites possibly serving as signal molecules. Likewise, catabolism of either threonine (mouse) or methionine (human) is required for growth and differentiation of ESCs because these AAs serve as precursors for donor molecules used in histone methylation and acetylation. Epigenetic mechanisms are recognized as critical steps in differentiation, and AA metabolism in ESCs appears to modulate these epigenetic processes. Recent reports also document that, in vitro, the nutrient composition of the culture medium in which ESCs are differentiated into embryoid bodies can influence lineage specification, leading to enrichment of a specific cell type. Although research designed to direct tissue specification of differentiating embryoid bodies in culture is still in its infancy, early results indicate that manipulation of the nutrient milieu can promote or suppress the formation of specific cell lineages. PMID:27422515

  17. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  18. Proteomic Investigation of Protein Profile Changes and Amino Acid Residue Level Modification in Cooked Lamb Meat: The Effect of Boiling.

    Science.gov (United States)

    Yu, Tzer-Yang; Morton, James D; Clerens, Stefan; Dyer, Jolon M

    2015-10-21

    Hydrothermal treatment (heating in water) is a common method of general food processing and preparation. For red-meat-based foods, boiling is common; however, how the molecular level effects of this treatment correlate to the overall food properties is not yet well-understood. The effects of differing boiling times on lamb meat and the resultant cooking water were here examined through proteomic evaluation. The longer boiling time was found to result in increased protein aggregation involving particularly proteins such as glyceraldehyde-3-phosphate dehydrogenase, as well as truncation in proteins such as in α-actinin-2. Heat-induced protein backbone cleavage was observed adjacent to aspartic acid and asparagine residues. Side-chain modifications of amino acid residues resulting from the heating, including oxidation of phenylalanine and formation of carboxyethyllysine, were characterized in the cooked samples. Actin and myoglobin bands from the cooked meat per se remained visible on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, even after significant cooking time. These proteins were also found to be the major source of observed heat-induced modifications. This study provides new insights into molecular-level modifications occurring in lamb meat proteins during boiling and a protein chemistry basis for better understanding the effect of this common treatment on the nutritional and functional properties of red-meat-based foods.

  19. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation

    DEFF Research Database (Denmark)

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian;

    2015-01-01

    and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards......Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process....... Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found...

  20. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected].

    Directory of Open Access Journals (Sweden)

    Francois-Pierre J Martin

    Full Text Available Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2 under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

  1. Sex Differences in Energy Metabolism Need to Be Considered with Lifestyle Modifications in Humans

    Directory of Open Access Journals (Sweden)

    Betty N. Wu

    2011-01-01

    Full Text Available Women have a higher proportion of body fat compared to men. However, women consume fewer kilojoules per kilogram lean mass and burn fat more preferentially during exercise compared with men. During gestation, women store even greater amounts of fat that cannot be solely attributed to increased energy intake. These observations suggest that the relationship between kilojoules consumed and kilojoules utilised is different in men and women. The reason for these sex differences in energy metabolism is not known; however, it may relate to sex steroids, differences in insulin resistance, or metabolic effects of other hormones such as leptin. When considering lifestyle modifications, sex differences in energy metabolism should be considered. Moreover, elucidating the regulatory role of hormones in energy homeostasis is important for understanding the pathogenesis of obesity and perhaps in the future may lead to ways to reduce body fat with less energy restriction.

  2. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina;

    2014-01-01

    Accumulation of damaged macromolecules, including irreversibly oxidized proteins, is a hallmark of cellular and organismal ageing. Failure of protein homesotasis is a major contributor to the age-related accumulation of damaged proteins. In skeletal muscle, tissue maintenance and regeneration....... Inactivation of the proteasome in aged cells appeared as a key contributor to the accumulation of such damaged proteins. Untargeted metabolomic profiling and functional analyses indicated glucose metabolism impairment in senescent cells, although mitochondrial respiration remained unaffected. A metabolic shift...... lipids for energy production. Such changes reflect alterations in membrane composition and dysregulation of sphingolipids signaling during senescence. This study establishes a new concept connecting oxidative protein modifications with the altered cellular metabolism associated with the senescent...

  3. Amino acid metabolism inhibits antibody-driven kidney injury by inducing autophagy.

    Science.gov (United States)

    Chaudhary, Kapil; Shinde, Rahul; Liu, Haiyun; Gnana-Prakasam, Jaya P; Veeranan-Karmegam, Rajalakshmi; Huang, Lei; Ravishankar, Buvana; Bradley, Jillian; Kvirkvelia, Nino; McMenamin, Malgorzata; Xiao, Wei; Kleven, Daniel; Mellor, Andrew L; Madaio, Michael P; McGaha, Tracy L

    2015-06-15

    Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response. The metabolic signal was driven by IFN-γ-mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on the eIF2α kinase general control nonderepressible 2 (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in glomeruli and reduced macrophage recruitment to the kidney during the incipient stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or treating mice with a GCN2 agonist induced autophagy and protected mice from nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven nephropathy showed increased IDO1 abundance and stress gene expression. Thus, these findings support the hypothesis that the IDO-GCN2 pathway in glomerular stromal cells is a critical negative feedback mechanism that limits inflammatory renal pathologic changes by inducing autophagy.

  4. A Branch Point of Streptomyces Sulfur Amino Acid Metabolism Controls the Production of Albomycin.

    Science.gov (United States)

    Kulkarni, Aditya; Zeng, Yu; Zhou, Wei; Van Lanen, Steven; Zhang, Weiwen; Chen, Shawn

    2016-01-01

    Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century. Although the productivity of S. griseus can be increased with random mutagenesis methods, understanding of Streptomyces sulfur amino acid (SAA) metabolism, which supplies a precursor for ABM biosynthesis, could lead to improved and stable production. We previously characterized the gene cluster (abm) in the genome-sequenced S. griseus strain and proposed that the sulfur atom of ABM is derived from either cysteine (Cys) or homocysteine (Hcy). The gene product, AbmD, appears to be an important link between primary and secondary sulfur metabolic pathways. Here, we show that propargylglycine or iron supplementation in growth media increased ABM production by significantly changing the relative concentrations of intracellular Cys and Hcy. An SAA metabolic network of S. griseus was constructed. Pathways toward increasing Hcy were shown to positively impact ABM production. The abmD gene and five genes that increased the Hcy/Cys ratio were assembled downstream of hrdBp promoter sequences and integrated into the chromosome for overexpression. The ABM titer of one engineered strain, SCAK3, in a chemically defined medium was consistently improved to levels ∼400% of the wild type. Finally, we analyzed the production and growth of SCAK3 in shake flasks for further process development. PMID:26519385

  5. EFFECTS OF CORDYCEPS SINENSIS PREPARATION ON BODY PROTEIN AND AMINO ACID METABOLISM IN PATIENTS AND RATS WITH CHRONIC RENAL FAILURE

    Institute of Scientific and Technical Information of China (English)

    朱淳; 刘强; 左静南; 朱汉威; 马济民

    2002-01-01

    Objective To study the effects of Cordyceps sinensis (CS) on the metabolism of body protein and intra-extracellular amino acids in patients with chronic renal failure( CRF) , and on the rates of protein synthesis in rats with CRF. Methods In patients with CRF, free amino acid concentrations in plasma and skeletal muscle before and after CS treatment were measured by the LKB-4400 amino acid automatic analytical instrument and the changes of body protein metabolism were observed by the method of 15 N-labeled glycine.Meanwhile, the rates of protein synthesis in liver ( SL % /d ) and muscle (SM%/d) of rats with CRF were determinedd by 3f-phenylalanine radioactive tracer. Results After patients with CRF were treated by CS, the Leu, lie, Thr , Lys, Cys, Tyr concentrations in plasma approached the normal levels. In one sample of skeletal muscle the Thr and Lys concentrations approached the normal, whereas both the intracellular and extracellular Val concentrations were still remarkably decreased as compared with the normal controls. Moreover, the nitrogen flow rate (Q) , rates of protein synthesis (S) and catabolism ( C) , and amino nitrogen utilization ratio (S/Q) in patients with CRF and the SL % /d and SM%/d in rats with CRF were significantly increased as compared with those before CS treatment. Conclusion CS can notably improve the amino acid metabolism, promote the body protein synthesis in patients with CRF , and increase the rates of SL % /d and SM%/d in rats with CRF.

  6. 3-(3-amino-3-carboxypropyl)-5,6-Dihydrouridine is one of two novel post-transcriptional modifications in tRNALys(UUU) from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Español, Yaiza; Giessing, Anders M B;

    2011-01-01

    the entire analysis. We identified modifications on 12 nucleosides in tRNA(Lys) (UUU), where U47 exhibited a novel modification, 3-(3-amino-3-carboxypropyl)-5,6-dihydrouridine, based on identical chromatographic retention and MS fragmentation as the synthetic nucleoside. A37 was observed in two versions....... Furthermore, the tRNA has to be investigated with single-nucleotide resolution in order to ensure complete mapping of all modifications. In the present work, we characterized tRNA(Lys) (UUU) from Trypanosoma brucei, and provide a complete overview of its post-transcriptional modifications. The first step...... of the unmodified tRNA revealed the modified residues. The modifications were further characterized at the nucleoside level by chromatographic retention time and fragmentation pattern upon higher-order tandem MS. Phylogenetic comparison with modifications in tRNA(Lys) from other organisms was used through...

  7. Molecule modification andmass deposition induced bythe implantation of lowenergy Fe+ ion beamsinto amino acids

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Fe+ ion beams with the energy of 110 keV were implanted into films of L(+)-cysteine (HSCH2CH(NH2)COOH). One of the single crystals grown in hydrochloric acid solution with the implanted samples through slow evaporation was structurally characterized by the X-ray crystallography. The crystal is monoclinic, space group C2, with a = 1.8534(4) nm, b = 0.5234(1) nm, c = 0.7212(1) nm, β= 103.72°, V = 0.67965(3) nm3, Z = 4, F(000) = 144.0, Dclac = 1.763 g@cm-3, μ(MoKα) = 1.06 mm-1, T = 293(2) K. R = 0.0379, wR = 0.0835 for 660 observed reflections (I > 2σ(I)). The structural formula of the crystal compound is (CH2CH(NH2)NO2)ClFe (Mr = 180.38 u). Products of heavy ion beam irradiation were purified and it was directly confirmed that the implanted Fe+ ions had been deposited in the novel molecules. The same doses of Fe+ ion beams of the same energy were implanted into films of L(+)-cysteine hydrochloride monohydrate. FTIR spectroscopy of the implanted samples proved that some of the original molecules were seriously damaged and significant modifications were induced.

  8. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary amino acid metabolism

    DEFF Research Database (Denmark)

    Larsen, Mogens; Galindo, C; Ouellet, D R;

    2015-01-01

    Nine Holstein cows with rumen cannulas and indwelling catheters in splanchnic blood vessels were used in a generalized randomized incomplete block design with repeated measures to study the effect of increased early postpartum AA supply on splanchnic and mammary AA metabolism. At calving, cows were......, and Lys tended to be greater for AA-CN, and the net PDV recovery of these infused AA ranged from 69 to 73%, indicating increased PDV metabolism with AA-CN. The fractional hepatic removal of these AA did not differ from zero and was unaffected by the increased supply. Consequently, the splanchnic release...... of these AA was approximately equivalent to their net PDV release for both CTRL and AA-CN. Overall, greater early postpartum AA supply increased milk and milk protein yields substantially based on increased mammary AA uptake. The PDV metabolism of branched-chain AA and Lys were increased, whereas it seemed...

  9. Effect of plant proteins and crystalline amino acid supplementation on postprandial plasma amino acid profiles and metabolic response in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Rolland, Marine; Larsen, Bodil Katrine; Holm, Jørgen;

    2015-01-01

    The use of aquafeeds formulated with plant protein sources supplemented with crystalline amino acids (CAAs) is believed to influence amino acid (AA) uptake patterns and AA metabolic fate. Oxygen consumption and ammonia excretion rates were measured in rainbow trout (468.5 +/- A 86.5 g) force fed 0.......75 % of their body mass with a diet based on either (1) fish meal (FM), (2) pea protein concentrate (PPC), or (3) pea protein concentrate supplemented with histidine, lysine, methionine and threonine (PPC+) to mimic FM AA profile. The specific dynamic action and nitrogen quotient (NQ) were calculated for 48 h...... to be caused by an unbalanced dietary AA profile and CAA supplementation, rather than inclusion of plant protein concentrate....

  10. Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification.

    Science.gov (United States)

    Chen, Chen; Wang, Jiahong; Cai, Ruiping; Yuan, Yanmeng; Guo, Zhanyun; Grewer, Christof; Zhang, Zhou

    2016-01-01

    Sodium-coupled neutral amino acid transporter 2 (SNAT2) belongs to solute carrier 38 (SLC38) family of transporters, which is ubiquitously expressed in mammalian tissues and mediates transport of small, neutral amino acids, exemplified by alanine(Ala, A). Yet structural data on SNAT2, including the relevance of intrinsic cysteine residues on structure and function, is scarce, in spite of its essential roles in many tissues. To better define the potential of intrinsic cysteines to form disulfide bonds in SNAT2, mutagenesis experiments and thiol-specific chemical modifications by N-ethylmaleimide (NEM) and methoxy-polyethylene glycol maleimide (mPEG-Mal, MW 5000) were performed, with or without the reducing regent dithiothreitol (DTT) treatment. Seven single mutant transporters with various cysteine (Cys, C) to alanine (Ala, A) substitutions, and a C245,279A double mutant were introduced to SNAT2 with a hemagglutinin (HA) tag at the C-terminus. The results showed that the cells expressing C245A or C279A were labeled by one equivalent of mPEG-Mal in the presence of DTT, while wild-type or all the other single Cys to Ala mutants were modified by two equivalents of mPEG-Mal. Furthermore, the molecular weight of C245,279A was not changed in the presence or absence of DTT treatment. The results suggest a disulfide bond between Cys245 and Cys279 in SNAT2 which has no effect on cell surface trafficking, as well as transporter function. The proposed disulfide bond may be important to delineate proximity in the extracellular domain of SNAT2 and related proteins. PMID:27355203

  11. Growth, feeding frequency, protein turnover, and amino acid metabolism in European lobster Homarus gammarus L.

    Science.gov (United States)

    Mente, E; Houlihan, D F; Smith, K

    2001-06-01

    The effect of feeding frequency on growth and protein metabolism in the European lobster, Homarus gammarus, was investigated. Fourth (IV) stage lobsters H. gammarus were fed individually a marine animal meal (herring/mussels meal) for 56 days. Feeding a daily ration equivalent to 10% of their body weight gave better growth than feeding daily rations of 5% and 20%. Protein synthesis rates were similar for the three food rations but protein growth rates were significantly lower and protein degradation rates highest in the 5% body weight per day ration group. The efficiency with which synthesised protein was retained as growth was found to be 38% in the in the 10% ratio group. Protein synthesis rates of lobsters were found to be lower than those for shrimps (Penaeus vannamei). The amino acid flux also suggests a lower protein conversion efficiency than shrimps P. vannamei. The results suggests that lobsters are slow, periodic feeders and that growth can be readily increased by manipulation of particular environmental factors such as feeding frequency. PMID:11351329

  12. Studies on Models,Patterns and Require-ments of Digestible Amino Acids for Layers by Nitrogen Metabolism

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The nitrogen (N) metabolic experiments were made to estimate separately amino acid requirements of 43~48 weeks old layers for maintenance, for protein accretion to estabolish models to estimate digestible amino acid requirements. The regression relationship of nitrogen retention vs amino acid intake was estimated for each amino acid by giving, at rate of N intake of 0.91, 0.52, 0.15 and 0.007g.kg-1 body-weight (W0.75) per d, the semi-synthetic diets was made specially deficient in one amino acid. From the regression coefficients, it was calculated that, for the accretion of 1 g protein, the dietary digestible amino acid requirements were (mg) Thr 63.1, Val 100.4, Met 39.9, Ile 88.6, Leu 114.3, Phe 63.2, Lys 87.0, His 20.5, Arg 87.9, Trp 21.4, Met+Cys 77.6, and Phe+Tyr 114.3. Daily amino acid requirements for N equilibrium were estimated to be (mg.kg-1W0.75 per day) Thr 50.6, Val 74.7, Met 30.3, ILe 66.7 Leu 81.4, Phe 44.8, Lys 60.5 His 14.7, Arg 73.9 ,Trp 17.3, Met+Cys 58.6, and Phe+Tyr 83.9 The dietary degestible amino acid patterns for protein accretion and N equilibrium were also proposed. The models of estimating digestible amino acid requirements for the different productions were developed.

  13. An Impaired Respiratory Electron Chain Triggers Down-regulation of the Energy Metabolism and De-ubiquitination of Solute Carrier Amino Acid Transporters.

    Science.gov (United States)

    Aretz, Ina; Hardt, Christopher; Wittig, Ilka; Meierhofer, David

    2016-05-01

    Hundreds of genes have been associated with respiratory chain disease (RCD), the most common inborn error of metabolism so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, ρ(0) cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. In this study, proteomic data sets including the post-translational modifications (PTMs) phosphorylation and ubiquitination were integrated with metabolomic data sets and selected enzyme activities in the osteosarcoma cell line 143B.TK(-) A shotgun based SILAC LC-MS proteomics and a targeted metabolomics approach was applied to elucidate the consequences of the ρ(0) state. Pathway and protein-protein interaction (PPI) network analyses revealed a nonuniform down-regulation of the respiratory electron chain, the tricarboxylic acid (TCA) cycle, and the pyruvate metabolism in ρ(0) cells. Metabolites of the TCA cycle were dysregulated, such as a reduction of citric acid and cis-aconitic acid (six and 2.5-fold), and an increase of lactic acid, oxalacetic acid (both twofold), and succinic acid (fivefold) in ρ(0) cells. Signaling pathways such as GPCR, EGFR, G12/13 alpha, and Rho GTPases were up-regulated in ρ(0) cells, which could be indicative for the mitochondrial retrograde response, a pathway of communication from mitochondria to the nucleus. This was supported by our phosphoproteome data, which revealed two main processes, GTPase-related signal transduction and cytoskeleton organization. Furthermore, a general de-ubiquitination in ρ(0) cells was observed, for example, 80S ribosomal proteins were in average threefold and SLC amino acid transporters fivefold de-ubiquitinated. The latter might cause the observed significant increase of amino acid levels in ρ(0) cells. We conclude that an elimination of the respiratory electron chain, e.g. mtDNA depletion, not only leads to an uneven down-regulation of mitochondrial energy pathways, but also

  14. The cyanobacterial amino acid β-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats.

    Science.gov (United States)

    Engskog, Mikael K R; Karlsson, Oskar; Haglöf, Jakob; Elmsjö, Albert; Brittebo, Eva; Arvidsson, Torbjörn; Pettersson, Curt

    2013-10-01

    The neurotoxic amino acid β-N-methylamino-l-alanine (BMAA) is produced by most cyanobacteria. BMAA is considered as a potential health threat because of its putative role in neurodegenerative diseases. We have previously observed cognitive disturbances and morphological brain changes in adult rodents exposed to BMAA during the development. The aim of this study was to characterize changes of major intermediary metabolites in serum following neonatal exposure to BMAA using a non-targeted metabolomic approach. NMR spectroscopy was used to obtain serum metabolic profiles from neonatal rats exposed to BMAA (40, 150, 460mg/kg) or vehicle on postnatal days 9-10. Multivariate data analysis of binned NMR data indicated metabolic pattern differences between the different treatment groups. In particular five metabolites, d-glucose, lactate, 3-hydroxybutyrate, creatine and acetate, were changed in serum of BMAA-treated neonatal rats. These metabolites are associated with changes in energy metabolism and amino acid metabolism. Further statistical analysis disclosed that all the identified serum metabolites in the lowest dose group were significantly (pmodel used in this study is so far the only animal model that displays significant biochemical and behavioral effects after a low short-term dose of BMAA. The demonstrated perturbation of intermediary metabolism may contribute to BMAA-induced developmental changes that result in long-term effects on adult brain function.

  15. Uptake of amino acids in brain tumours using positron emission tomography as an indicator for assessing metabolic activity and malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Schober, O.; Meyer, G.J.; Duden, C.; Lauenstein, L.; Niggemann, J.; Mueller, J.A.; Hundeshagen, H.; Gaab, M.R.; Dietz, H.; Becker, H.

    1987-11-01

    Diagnosis and post-therapeutic follow-up of tumour patients necessitates morphological and particularly functional imaging methods. For the latter approach positron emission tomography has proven a valid tool for the measurement of perfusion, of energy consumption parameters such as oxygen extraction, glucose metabolism and amino acid uptake. However, neither perfusion nor energy consumption parameters have yielded unambiguous information on the clinical status of various tumours in respect of their malignancy and their growth status. It is shown in this paper that amino acid uptake seems to be a valid measure for the functional activity of tumour tissue for a broad range of neoplasms. The uptake of /sup 11/C-L-Methionine was measured in 33 patients having various brain tumours, and was compared with 6 patients who had an infarction, and with 8 patients suffering from arachnoidal cysts. The amino acid uptake correlated well with the histological grading of the tumours and the clinical status of the patient. The uptake was well differentiated against metabolically inactive lesions. Parallel investigations on the uptake mechanisms of amino acids in an animal model have shown that transport phenomena regulate the uptake rather than protein synthesis rates. However, protein synthesis may nevertheless exercise a control function on the transport process.

  16. [3H]-amino acid uptake and metabolic studies on Gigantocotyle explanatum and Gastrothylax crumenifer (Digenea: Paramphistomidae)

    International Nuclear Information System (INIS)

    The amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer utilize leucine, alanine, proline and methionine during in vitro incubations. Autoradiography on sections of these flukes reveal a time-dependent differential incorporation of tritium-labelled amino acids in various tissues. The tegument appears to be the primary surface through which amino acids are absorbed. Following absorption, the reappearance of [3H]-leucine and [3H]-alanine on the tegumental surface during late chase periods indicates their possible involvement in tegumental secretion. A combination of diffusion and carrier-mediated uptake, possibly involving gamma-glutamyl transpeptidase, is indicated. The transport loci show differences in carrier-affinity (Kt) and maximum uptake velocities (Vmax) for amino acids under study, which suggest multiple transport molecules. Metabolic studies reveal that aspartate, alanine, ornithine, proline, leucine and methionine undergo transamination through 2-oxoglutarate-linked transaminases, distributed in the cytosolic and mitochondrial fractions of G. explanatum and G. crumenifer. With the exception of alanine transaminase, the enzyme levels in the cytosolic fraction were higher than the mitochondrial fraction of the two amphistomes. Predominantly cytosolic glutamate dehydrogenase which was comparatively higher in G. explanatum, catalyse amination of alpha-ketoglutarate. A high level of cytosolic arginase alone does not indicate a functional urea cycle. A tentative pathway of amino acid metabolism in these amphistomes is proposed

  17. Constraint-based strain design using continuous modifications (CosMos) of flux bounds finds new strategies for metabolic engineering.

    Science.gov (United States)

    Cotten, Cameron; Reed, Jennifer L

    2013-05-01

    In recent years, a growing number of metabolic engineering strain design techniques have employed constraint-based modeling to determine metabolic and regulatory network changes which are needed to improve chemical production. These methods use systems-level analysis of metabolism to help guide experimental efforts by identifying deletions, additions, downregulations, and upregulations of metabolic genes that will increase biological production of a desired metabolic product. In this work, we propose a new strain design method with continuous modifications (CosMos) that provides strategies for deletions, downregulations, and upregulations of fluxes that will lead to the production of the desired products. The method is conceptually simple and easy to implement, and can provide additional strategies over current approaches. We found that the method was able to find strain design strategies that required fewer modifications and had larger predicted yields than strategies from previous methods in example and genome-scale networks. Using CosMos, we identified modification strategies for producing a variety of metabolic products, compared strategies derived from Escherichia coli and Saccharomyces cerevisiae metabolic models, and examined how imperfect implementation may affect experimental outcomes. This study gives a powerful and flexible technique for strain engineering and examines some of the unexpected outcomes that may arise when strategies are implemented experimentally.

  18. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary amino acid metabolism.

    Science.gov (United States)

    Larsen, M; Galindo, C; Ouellet, D R; Maxin, G; Kristensen, N B; Lapierre, H

    2015-11-01

    Nine Holstein cows with rumen cannulas and indwelling catheters in splanchnic blood vessels were used in a generalized randomized incomplete block design with repeated measures to study the effect of increased early postpartum AA supply on splanchnic and mammary AA metabolism. At calving, cows were blocked according to parity (second and third or greater) and allocated to 2 treatments: abomasal infusion of water (CTRL; n=4) or free AA with casein profile (AA-CN; n=5) in addition to a basal diet. The AA-CN infusion started with half of the maximal dose at the calving day (1 d in milk; DIM) and then steadily decreased from 791 to 226 g/d until 29 DIM. On 5, 15, and 29 DIM, 6 sample sets of arterial, portal, hepatic, and mammary blood were taken at 45-min intervals. Over the whole period, increasing AA supply increased milk (+7.8 ± 1.3 kg/d) and milk protein yields (+220 ± 65 g/d) substantially. The increased milk yield was not supported by greater dry matter intake (DMI) as, overall, DMI decreased with AA-CN (-1.6 ± 0.6 kg/d). Arterial concentrations of essential AA were greater for AA-CN compared with CTRL. The net portal-drained viscera (PDV) release of His, Met, and Phe was greater for AA-CN compared with CTRL, and the net PDV recovery of these infused AA ranged from 72 to 102% once changes in DMI were accounted for. The hepatic removal of these AA was increased equivalently to the increased net PDV release, resulting in an unaltered net splanchnic release. The net PDV release of Ile, Leu, Val, and Lys tended to be greater for AA-CN, and the net PDV recovery of these infused AA ranged from 69 to 73%, indicating increased PDV metabolism with AA-CN. The fractional hepatic removal of these AA did not differ from zero and was unaffected by the increased supply. Consequently, the splanchnic release of these AA was approximately equivalent to their net PDV release for both CTRL and AA-CN. Overall, greater early postpartum AA supply increased milk and milk protein

  19. Global Proteome Analyses of Lysine Acetylation and Succinylation Reveal the Widespread Involvement of both Modification in Metabolism in the Embryo of Germinating Rice Seed.

    Science.gov (United States)

    He, Dongli; Wang, Qiong; Li, Ming; Damaris, Rebecca Njeri; Yi, Xingling; Cheng, Zhongyi; Yang, Pingfang

    2016-03-01

    Regulation of rice seed germination has been shown to mainly occur at post-transcriptional levels, of which the changes on proteome status is a major one. Lysine acetylation and succinylation are two prevalent protein post-translational modifications (PTMs) involved in multiple biological processes, especially for metabolism regulation. To investigate the potential mechanism controlling metabolism regulation in rice seed germination, we performed the lysine acetylation and succinylation analyses simultaneously. Using high-accuracy nano-LC-MS/MS in combination with the enrichment of lysine acetylated or succinylated peptides from digested embryonic proteins of 24 h after imbibition (HAI) rice seed, a total of 699 acetylated sites from 389 proteins and 665 succinylated sites from 261 proteins were identified. Among these modified lysine sites, 133 sites on 78 proteins were commonly modified by two PTMs. The overlapped PTM sites were more likely to be in polar acidic/basic amino acid regions and exposed on the protein surface. Both of the acetylated and succinylated proteins cover nearly all aspects of cellular functions. Ribosome complex and glycolysis/gluconeogenesis-related proteins were significantly enriched in both acetylated and succinylated protein profiles through KEGG enrichment and protein-protein interaction network analyses. The acetyl-CoA and succinyl-CoA metabolism-related enzymes were found to be extensively modified by both modifications, implying the functional interaction between the two PTMs. This study provides a rich resource to examine the modulation of the two PTMs on the metabolism pathway and other biological processes in germinating rice seed. PMID:26767346

  20. Expression profiles of the genes associated with metabolism and transport of amino acids and their derivatives in rat liver regeneration.

    Science.gov (United States)

    Xu, C S; Chang, C F

    2008-01-01

    Amino acids (AA) are components of protein and precursors of many important biological molecules. To address effects of the genes associated with metabolism and transport of AA and their derivatives during rat liver regeneration (LR), we firstly obtained the above genes by collecting databases data and retrieving related thesis, and then analyzed their expression profiles during LR using Rat Genome 230 2.0 array. The LR-associated genes were identified by comparing the gene expression difference between partial hepatectomy (PH) and sham-operation (SO) rat livers. It was approved that 134 genes associated with metabolism of AA and their derivatives and 26 genes involved in transport of them were LR-associated. The initially and totally expressing number of these genes occurring in initial phase of LR (0.5-4 h after PH), G0/G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction of liver tissue (72-168 h after PH) were respectively 76, 17, 79, 5 and 162, 89, 564, 195, illustrating that these LR-associated genes were initially expressed mainly in initial stage, and functioned in different phases. Frequencies of up-regulation and down-regulation of them being separately 564 and 357 demonstrated that genes up-regulated outnumbered those down-regulated. Categorization of their expression patterns into 22 types implied the diversity of cell physiological and biochemical activities. According to expression changes and patterns of the above-mentioned genes in LR, it was presumed that histidine biosynthesis in the metaphase and anaphase, valine metabolism in the anaphase, and metabolism of glutamate, glutamine, asparate, asparagine, methionine, alanine, leucine and aromatic amino acid almost were enhanced in the whole LR; as for amino acid derivatives, transport of neutral amino acids, urea, gamma-aminobutyric acid, betaine and taurine, metabolism of dopamine, heme, S-adenosylmethionine, thyroxine, and

  1. Effect of Lead on Microorganisms with Respect to Antibiogram, Glucose and Amino Acid Metabolism

    Directory of Open Access Journals (Sweden)

    Aishwarya Pradeep Rao

    2014-07-01

    Full Text Available Background: Lead poisoning is a prevalent health hazard in today's world of industrialization and is gaining the concern of medical professionals globally. The first organisms in the biosphere to be affected by this are the microorganisms. Many studies have established that metal tolerance is accompanied by antibiotic resistance as both the genes are present on plasmids. Aims and Objectives: The study was conducted to identify the concentrations of lead at which the microbial growth and antibiotic sensitivity was affected and also to identify whether any of the key metabolic activities were influenced. Microorganisms like Escherichia coli, Staphylococcus aureus and Candida albicans. Pseudomonas aeruginosa were chosen due to their increasing importance as a potent hospital acquired pathogen. Material and Methods: American Type Culture Collection (ATCC strains were chosen and exposed to varying concentrations of lead acetate ranging from 1 to 1000 ppm. The growth was quantitatively analyzed spectrophotometrically at 600 nm. The antibiogram was done using disk diffusion method. The sugar fermenting property and the amino acid utilization was studied as they are the basic requirements for growth of any microorganism. Results: On exposure to lead, a decrease in the growth was seen with the three organisms but the growth pattern was different with Pseudomonas as it showed a sudden increase at 100 ppm accompanied by the production of H S at certain concentrations. The 2 antibiotic sensitivity tests which were carried out after exposure to lead, showed a resistance pattern to the β lactam group of antibiotics, hence implying that tolerance to the heavy metal affected the sensitivity of these organisms to the antibiotics. The biochemical tests showed no change in the presence of lead. Lead may exist in the soil in various concentrations but may exert a selective pressure only at certain concentrations. It has been established that a pattern exists

  2. Comparative analysis of RNA regulatory elements of amino acid metabolism genes in Actinobacteria

    Directory of Open Access Journals (Sweden)

    Gelfand Mikhail S

    2005-10-01

    Full Text Available Abstract Background Formation of alternative structures in mRNA in response to external stimuli, either direct or mediated by proteins or other RNAs, is a major mechanism of regulation of gene expression in bacteria. This mechanism has been studied in detail using experimental and computational approaches in proteobacteria and Firmicutes, but not in other groups of bacteria. Results Comparative analysis of amino acid biosynthesis operons in Actinobacteria resulted in identification of conserved regions upstream of several operons. Classical attenuators were predicted upstream of trp operons in Corynebacterium spp. and Streptomyces spp., and trpS and leuS genes in some Streptomyces spp. Candidate leader peptides with terminators were observed upstream of ilvB genes in Corynebacterium spp., Mycobacterium spp. and Streptomyces spp. Candidate leader peptides without obvious terminators were found upstream of cys operons in Mycobacterium spp. and several other species. A conserved pseudoknot (named LEU element was identified upstream of leuA operons in most Actinobacteria. Finally, T-boxes likely involved in the regulation of translation initiation were observed upstream of ileS genes from several Actinobacteria. Conclusion The metabolism of tryptophan, cysteine and leucine in Actinobacteria seems to be regulated on the RNA level. In some cases the mechanism is classical attenuation, but in many cases some components of attenuators are missing. The most interesting case seems to be the leuA operon preceded by the LEU element that may fold into a conserved pseudoknot or an alternative structure. A LEU element has been observed in a transposase gene from Bifidobacterium longum, but it is not conserved in genes encoding closely related transposases despite a very high level of protein similarity. One possibility is that the regulatory region of the leuA has been co-opted from some element involved in transposition. Analysis of phylogenetic patterns

  3. The cerebral metabolism of amino acids and related metabolites as studied by 13C and 14C labelling

    International Nuclear Information System (INIS)

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by 13C-and 14C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [13C[acetate, it was shown that glial cells export ∼60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [13C[glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of 13CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs

  4. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

    Energy Technology Data Exchange (ETDEWEB)

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.

  5. 3-Self behavior modification programs base on the PROMISE Model for clients at metabolic risk.

    Science.gov (United States)

    Intarakamhang, Ungsinun

    2011-12-29

    The objectives of this mixed methods research were 1) to study effects of the health behavior modification program (HBMP) conducted under the principles of the PROMISE Model and the CIPP Model and 2) to compare the 3-self health behaviors and the biomedical indicators before with after the program completion. During the program, three sample groups including 30 program leaders, 30 commanders and 120 clients were assessed, and there were assessments taken on 4,649 volunteers who were at risk of metabolic syndrome before and after the program conducted in 17 hospitals. The collected data were analyzed by the t-test and the path analysis. The research instruments were questionnaires used for program evaluation, structuralized interview forms, and questionnaires used for 3-self health behavior assessment. The findings were as follows: 1) During the program, the assessment result deriving from comparing the overall opinions toward the program among the three sample groups showed no difference (F=2.219), 2) The program management factors based on the PROMISE Model (positive reinforcement, optimism, context, and process or activity provision) had an overall influence on the product or success of the HBMP (pself-efficacy, self-regulation, and self-care) were significantly higher than those appeared before the participation (p< 0.05), and their biomedical indicators (BMI, blood pressure, waistline, blood glucose, lipid profiles, cholesterol, and HbA1c) were significantly lower than those measured before the program (p< 0.05).

  6. Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

    Science.gov (United States)

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2015-11-01

    Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

  7. Comparison of amino acid oxidation and urea metabolism in haemodialysis patients during fasting and meal intake

    NARCIS (Netherlands)

    Veeneman, JM; Kingma, HA; Stellaard, F; de Jong, PE; Reijngoud, DJ; Huisman, RM

    2004-01-01

    Background. The PNA (protein equivalent of nitrogen appearance) is used to calculate protein intake from urea kinetics. One of the essential assumptions in the calculation of PNA is that urea accumulation in haemodialysis (HD) patients is equivalent to amino acid oxidation. However, urea is hydrolys

  8. Cloning of NruI and Sbo13I restriction and modification sstems in E. coli and amino acid sequence comparison of M.NruI and M.Sbo13I with other amino-methyltransferases

    Directory of Open Access Journals (Sweden)

    Benner Jack

    2010-05-01

    Full Text Available Abstract Background NruI and Sbo13I are restriction enzyme isoschizomers with the same recognition sequence 5' TCG↓CGA 3' (cleavage as indicated↓. Here we report the cloning of NruI and Sbo13I restriction-modification (R-M systems in E. coli. The NruI restriction endonuclease gene (nruIR was cloned by PCR and inverse PCR using primers designed from the N-terminal amino acid sequence. The NruI methylase gene (nruIM was derived by inverse PCR walking. Results The amino acid sequences of NruI endonuclease and methylase are very similar to the Sbo13I R-M system which has been cloned and expressed in E. coli by phage selection of a plasmid DNA library. Dot blot analysis using rabbit polyclonal antibodies to N6mA- or N4mC-modified DNA indicated that M.NruI is possibly a N6mA-type amino-methyltransferase that most likely modifies the external A in the 5' TCGCGA 3' sequence. M.Sbo13I, however, is implicated as a probable N4mC-type methylase since plasmid carrying sbo13IM gene is not restricted by Mrr endonuclease and Sbo13I digestion is not blocked by Dam methylation of the overlapping site. The amino acid sequence of M.NruI and M.Sbo13I did not show significant sequence similarity to many known amino-methyltransferases in the α, β, and γ groups, except to a few putative methylases in sequenced microbial genomes. Conclusions The order of the conserved amino acid motifs (blocks in M.NruI/M.Sbo13I is similar to the γ. group amino-methyltranferases, but with two distinct features: In motif IV, the sequence is DPPY instead of NPPY; there are two additional conserved motifs, IVa and Xa as extension of motifs IV and X, in this family of enzymes. We propose that M.NruI and M.Sbo13I form a subgroup in the γ group of amino-methyltransferases.

  9. PGC-1α-Mediated Branched-Chain Amino Acid Metabolism in the Skeletal Muscle

    OpenAIRE

    Yukino Hatazawa; Miki Tadaishi; Yuta Nagaike; Akihito Morita; Yoshihiro Ogawa; Osamu Ezaki; Takako Takai-Igarashi; Yasuyuki Kitaura; Yoshiharu Shimomura; Yasutomi Kamei; Shinji Miura

    2014-01-01

    Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellula...

  10. Arsenite tolerance in rice (Oryza sativa L.) involves coordinated role of metabolic pathways of thiols and amino acids.

    Science.gov (United States)

    Tripathi, Preeti; Tripathi, Rudra Deo; Singh, Rana Pratap; Dwivedi, Sanjay; Chakrabarty, Debasis; Trivedi, Prabodh K; Adhikari, Bijan

    2013-02-01

    Thiolic ligands and several amino acids (AAs) are known to build up in plants against heavy metal stress. In the present study, alteration of various AAs in rice and its synchronized role with thiolic ligand was explored for arsenic (As) tolerance and detoxification. To understand the mechanism of As tolerance and stress response, rice seedlings of one tolerant (Triguna) and one sensitive (IET-4786) cultivar were exposed to arsenite (0-25 μM) for 7 days for various biochemical analyses using spectrophotometer, HPLC and ICPMS. Tolerant and sensitive cultivars respond differentially in terms of thiol metabolism, essential amino acids (EEAs) and nonessential amino acids (NEEAs) vis-á-vis As accumulation. Thiol biosynthesis-related enzymes were positively correlated to As accumulation in Triguna. Conversely, these enzymes, cysteine content and GSH/GSSG ratio declined significantly in IET-4786 upon As exposure. The level of identified phytochelatin (PC) species (PC(2), PC(3) and PC(4)) and phytochelatin synthase activity were also more pronounced in Triguna than IET-4786. Nearly all EAAs were negatively affected by As-induced oxidative stress (except phenylalanine in Triguna), but more significantly in IET-4786 than Triguna. However, most of the stress-responsive NEAAs like glutamic acid, histidine, alanine, glycine, tyrosine, cysteine and proline were enhanced more prominently in Triguna than IET-4786 upon As exposure. The study suggests that IET-4786 appears sensitive to As due to reduction of AAs and thiol metabolic pathway. However, a coordinated response of thiolic ligands and stress-responsive AAs seems to play role for As tolerance in Triguna to achieve the effective complexation of As by PCs.

  11. Presymptomatic Alterations in Amino Acid Metabolism and DNA Methylation in the Cerebellum of a Murine Model of Niemann-Pick Type C Disease.

    Science.gov (United States)

    Kennedy, Barry E; Hundert, Amos S; Goguen, Donna; Weaver, Ian C G; Karten, Barbara

    2016-06-01

    The fatal neurodegenerative disorder Niemann-Pick type C (NPC) is caused in most cases by mutations in NPC1, which encodes the late endosomal NPC1 protein. Loss of NPC1 disrupts cholesterol trafficking from late endosomes to the endoplasmic reticulum and plasma membrane, causing cholesterol accumulation in late endosomes/lysosomes. Neurons are particularly vulnerable to this cholesterol trafficking defect, but the pathogenic mechanisms through which NPC1 deficiency causes neuronal dysfunction remain largely unknown. Herein, we have investigated amino acid metabolism in cerebella of NPC1-deficient mice at different stages of NPC disease. Imbalances in amino acid metabolism were evident from increased branched chain amino acid and asparagine levels and altered expression of key enzymes of glutamine/glutamate metabolism in presymptomatic and early symptomatic NPC1-deficient cerebellum. Increased levels of several amino acid intermediates of one-carbon metabolism indicated disturbances in folate and methylation pathways. Alterations in DNA methylation were apparent in decreased expression of DNA methyltransferase 3a and methyl-5'-cytosine-phosphodiester-guanine-domain binding proteins, reduced 5-methylcytosine immunoreactivity in the molecular and Purkinje cell layers, demethylation of genome-wide repetitive LINE-1 elements, and hypermethylation in specific promoter regions of single-copy genes in NPC1-deficient cerebellum at early stages of the disease. Alterations in amino acid metabolism and epigenetic changes in the cerebellum at presymptomatic stages of NPC disease represent previously unrecognized mechanisms of NPC pathogenesis. PMID:27083515

  12. Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

    Science.gov (United States)

    Tischler, M. E.; Jaspers, S. R.

    1985-01-01

    Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

  13. Effect of Amino Acid Residue and Oligosaccharide Chain Chemical Modifications on Spectral and Hemagglutinating Activity of Millettia dielsiana Harms. ex Diels. Lectin

    Institute of Scientific and Technical Information of China (English)

    Shun GAO; Jie AN; Chuan-Fang WU; Ying GU; Fang CHEN; Yuan YU; Qia-Qing WU; Jin-Ku BAO

    2005-01-01

    The effects of modifying the carbohydrate chain and amino acids on the conformation and activity of Millettia dielsiana Harms. ex Diels. lectin (MDL) were studied by hemagglutination, fluorescence and circular dichroism analysis. The modification of tryptophan residues led to a compete loss of hemagglutinating activity; however, the addition of mannose was able to prevent this loss of activity. The results indicate that two tryptophan residues are involved in the carbohydrate-binding site. Modifications of the carboxyl group residues produced an 80% loss of activity, but the presence of mannose protected against the modification. The results suggest that the carboxyl groups of aspartic and glutamic acids are involved in the carbohydrate-binding site of the lectin. However, oxidation of the carbohydrate chain and modification of the histidine and arginine residues did not affect the hemagglutinating activity of MDL. Fluorescence studies of MDL indicate that tryptophan residues are present in a relatively hydrophobic region, and the binding of mannose to MDL could quench tryptophan fluorescence without any change in λmax. The circular dichroism spectrum showed that all of these modifications affected the conformation of the MDL molecule to different extents, except the modification of arginine residues. Fluorescence quenching showed that acrylamide and iodoacetic acids are able to quench 77% and 98% of the fluorescence of tryptophan in MDL, respectively.However, KI produced a barely perceptible effect on the fluorescence of MDL, even when the concentration of I- was 0.15 M. This demonstrates that most of tryptophan residues are located in relatively hydrophobic or negatively charged areas near the surface of the MDL molecule.

  14. Inhibition of aconitase in citrus fruit callus results in a metabolic shift towards amino acid biosynthesis

    NARCIS (Netherlands)

    Degu, A.; Hatew, B.; Nunes-Nesi, A.; Shlizerman, L.; Zur, N.; Fernie, A.R.; Blumwald, E.; Sadka, A.

    2011-01-01

    Citrate, a major determinant of citrus fruit quality, accumulates early in fruit development and declines towards maturation. The isomerization of citrate to isocitrate, catalyzed by aconitase is a key step in acid metabolism. Inhibition of mitochondrial aconitase activity early in fruit development

  15. Training and muscle ammonia and amino acid metabolism in humans during prolonged exercise

    DEFF Research Database (Denmark)

    Graham, T E; Turcotte, L P; Kiens, Bente;

    1995-01-01

    .4 +/- 6.8 mmol/kg wet wt in Tr and Utr, respectively. Tr had greater (P catabolism. The efflux of NH3 and Gln was much...... greater than that expected from AMP deamination, suggesting that deamination of AA was occurring. Many of the AA responses use Glu, and Tr maintained the intramuscular Glu pool at a higher concentration (P catabolism and/or AA transaminations....... Under these conditions, prolonged dynamic knee extensor exercise is associated with a large release of alpha-amino moieties both as NH3 and as Gln as well as a net protein catabolism; these responses are similar in Tr and Utr....

  16. Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

    Directory of Open Access Journals (Sweden)

    Sebastiano Collino

    Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

  17. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation.

    Science.gov (United States)

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

    2015-03-01

    Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans

  18. Maternal Factors Are Associated with the Expression of Placental Genes Involved in Amino Acid Metabolism and Transport.

    Directory of Open Access Journals (Sweden)

    Pricilla E Day

    Full Text Available Maternal environment and lifestyle factors may modify placental function to match the mother's capacity to support the demands of fetal growth. Much remains to be understood about maternal influences on placental metabolic and amino acid transporter gene expression. We investigated the influences of maternal lifestyle and body composition (e.g. fat and muscle content on a selection of metabolic and amino acid transporter genes and their associations with fetal growth.RNA was extracted from 102 term Southampton Women's Survey placental samples. Expression of nine metabolic, seven exchange, eight accumulative and three facilitated transporter genes was analyzed using quantitative real-time PCR.Increased placental LAT2 (p = 0.01, y+LAT2 (p = 0.03, aspartate aminotransferase 2 (p = 0.02 and decreased aspartate aminotransferase 1 (p = 0.04 mRNA expression associated with pre-pregnancy maternal smoking. Placental mRNA expression of TAT1 (p = 0.01, ASCT1 (p = 0.03, mitochondrial branched chain aminotransferase (p = 0.02 and glutamine synthetase (p = 0.05 was positively associated with maternal strenuous exercise. Increased glutamine synthetase mRNA expression (r = 0.20, p = 0.05 associated with higher maternal diet quality (prudent dietary pattern pre-pregnancy. Lower LAT4 (r = -0.25, p = 0.05 and aspartate aminotransferase 2 mRNA expression (r = -0.28, p = 0.01 associated with higher early pregnancy diet quality. Lower placental ASCT1 mRNA expression associated with measures of increased maternal fat mass, including pre-pregnancy BMI (r = -0.26, p = 0.01. Lower placental mRNA expression of alanine aminotransferase 2 associated with greater neonatal adiposity, for example neonatal subscapular skinfold thickness (r = -0.33, p = 0.001.A number of maternal influences have been linked with outcomes in childhood, independently of neonatal size; our finding of associations between placental expression of transporter and metabolic genes and maternal smoking

  19. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism.

    Science.gov (United States)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N; Bibby, Kyle J; Stolz, Donna B; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L; Barchowsky, Aaron; Stolz, John F

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes.

  20. Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women.

    Science.gov (United States)

    Boirie, Y; Gachon, P; Cordat, N; Ritz, P; Beaufrère, B

    2001-02-01

    Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of D-[6, 6-(2)H(2)]glucose and L-[1-(13)C]leucine in 14 young (Y; 24.0 +/- 0.9 yr; mean +/- SEM, 20.5 +/- 0.4 kg/m(2)) and 12 healthy elderly subjects (E; 69.4 +/- 0.6 yr; 24.6 +/- 0.8 kg/m(2)) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg.min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (-13.5 +/- 1.4% vs. -8.8 +/- 1.3%, Y vs. E, P CL2 (-22.0 +/- 1.4% vs. -18.8 +/- 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects. PMID:11158022

  1. A new strategy for the selective determination of D-amino acids: enzymatic and chemical modifications for pre-column derivatization.

    Science.gov (United States)

    Oguri, Shigeyuki; Nomura, Michiko; Fujita, Youko

    2005-06-17

    A new strategy for the selective determination of D-amino acids (DAAs) employing a pre-column derivatization was designed with concepts based on both enzymatic and chemical modifications. Selective determination of DAAs was accomplished by following: DAA was enzymatically modified with D-amino acid oxidase (DAAO: EC 1.4.3.3) to form an alpha-keto acid. Subsequently, resulting alpha-keto acid was detected by high-performance liquid chromatography (HPLC) after chemical modification with o-phenylenediamine (PDA) in the presence of 2-mercaptoethanol (2ME) to give the corresponding quinoxalinol derivative (PDA-alpha-keto acid derivative). After optimizing the pre-column derivatization and HPLC separation, five peaks corresponding to DAAs (D-alanine, D-leucine, D-methionine, D-phenylalanine, D-valine (as the standard mixture of DAAs in this paper) were separately eluted and monitored by means of a conventional HPLC system with a gradient elution on octadecyl silica gel (ODS) column and a fluorescence detector (Ex.: 341 nm, Em.: 413 nm), respectively. It was confirmed that the present method was incapable of detecting L-amino acids (LAA) when a sample solution consisting of both LAAs and DAAs was examined. The linearity of the peak-area responses to their concentration range of DAAs from 10 to 500 microM is 0.994-1.000, and their detection limits were 0.2-1 microM (signal/noise = 3). When this method was applied to a methanolic extract of short-necked clams, Ruditapes philippinarum (in Japanese, Asari), a big peak, corresponding to D-alanine was detected, corresponding to 2.9 mg/g D-alanine. In this paper, we present an example of pre-column derivatization method that was newly configured to take into account both the biological and chemical properties of the substances in question. PMID:16007981

  2. Protein homeostasis disorders of key enzymes of amino acids metabolism: mutation-induced protein kinetic destabilization and new therapeutic strategies.

    Science.gov (United States)

    Pey, Angel L

    2013-12-01

    Many inborn errors of amino acids metabolism are caused by single point mutations affecting the ability of proteins to fold properly (i.e., protein homeostasis), thus leading to enzyme loss-of-function. Mutations may affect protein homeostasis by altering intrinsic physical properties of the polypeptide (folding thermodynamics, and rates of folding/unfolding/misfolding) as well as the interaction of partially folded states with elements of the protein homeostasis network (such as molecular chaperones and proteolytic machineries). Understanding these mutational effects on protein homeostasis is required to develop new therapeutic strategies aimed to target specific features of the mutant polypeptide. Here, I review recent work in three different diseases of protein homeostasis associated to inborn errors of amino acids metabolism: phenylketonuria, inherited homocystinuria and primary hyperoxaluria type I. These three different genetic disorders involve proteins operating in different cell organelles and displaying different structural complexities. Mutations often decrease protein kinetic stability of the native state (i.e., its half-life for irreversible denaturation), which can be studied using simple kinetic models amenable to biophysical and biochemical characterization. Natural ligands and pharmacological chaperones are shown to stabilize mutant enzymes, thus supporting their therapeutic application to overcome protein kinetic destabilization. The role of molecular chaperones in protein folding and misfolding is also discussed as well as their potential pharmacological modulation as promising new therapeutic approaches. Since current available treatments for these diseases are either burdening or only successful in a fraction of patients, alternative treatments must be considered covering studies from protein structure and biophysics to studies in animal models and patients.

  3. Second-tier test for quantification of underivatized amino acids in dry blood spot for metabolic diseases in newborn screening.

    Science.gov (United States)

    Wang, Chunyan; Zhu, Hongbin; Zhang, Wenyan; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

    2013-02-01

    The quantitative analysis of amino acids (AAs) in single dry blood spot (DBS) samples is an important issue for metabolic diseases as a second-tier test in newborn screening. An analytical method for quantifying underivatized AAs in DBS was developed by using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The sample preparation in this method is simple and ion-pairing agent is not used in the mobile phase that could avoid ion suppression, which happens in mass spectrometry and avoids damage to the column. Through chromatographic separation, some isomeric compounds could be identified and quantified, which cannot be solved through only appropriate multiple reactions monitoring transitions by MS/MS. The concentrations of the different AAs were determined using non-deuterated internal standard. All calibration curves showed excellent linearity within test ranges. For most of the amino acids the accuracy of extraction recovery was between 85.3 and 115 %, and the precision of relative standard deviation was <7.0 %. The 35 AAs could be identified in DBS specimens by the developed LC-MS/MS method in 17-19 min, and eventually 24 AAs in DBS were quantified. The results of the present study prove that this method as a second-tier test in newborn screening for metabolic diseases could be performed by the quantification of free AAs in DBS using the LC-MS/MS method. The assay has advantages of high sensitive, specific, and inexpensive merits because non-deuterated internal standard and acetic acid instead of ion-pairing agent in mobile phase are used in this protocol.

  4. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction.

    Science.gov (United States)

    Thackeray, James T; Bankstahl, Jens P; Wang, Yong; Wollert, Kai C; Bengel, Frank M

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (ptranslation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  5. Proteomic investigation of protein profile changes and amino acid residue-level modification in cooked lamb longissimus thoracis et lumborum: The effect of roasting.

    Science.gov (United States)

    Yu, Tzer-Yang; Morton, James D; Clerens, Stefan; Dyer, Jolon M

    2016-09-01

    Protein modifications of meat cooked by typical dry-heat methods (e.g., roasting) are currently not well understood. The present study utilised a shotgun proteomic approach to examine the molecular-level effect of roasting on thin lamb longissimus thoracis et lumborum patties, in terms of changes to both the protein profile and amino acid residue side-chain modifications. Cooking caused aggregation of actin, myosin heavy chains and sarcoplasmic proteins. Longer roasting time resulted in significantly reduced protein extractability as well as protein truncation involving particularly a number of myofibrillar and sarcoplasmic proteins, e.g., 6-phosphofructokinase, beta-enolase, l-lactate dehydrogenase A chain, alpha-actinin-3, actin and possibly myosin heavy chains. Modifications that have potential influence on nutritional properties, including carboxyethyllysine and a potentially glucose-derived N-terminal Amadori compound, were observed in actin and myoglobin after roasting. This study provided new insights into molecular changes resulting from the dry-heat treatment of meat, such as commonly used in food preparation. PMID:27150797

  6. Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

    OpenAIRE

    Petri Wiklund; Xiaobo Zhang; Satu Pekkala; Reija Autio; Lingjia Kong; Yifan Yang; Sirkka Keinänen-Kiukaanniemi; Markku Alen; Sulin Cheng

    2016-01-01

    Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectr...

  7. Genetic diversity in proteolytic enzymes and amino acid metabolism among Lactobacillus helveticus strains

    DEFF Research Database (Denmark)

    Broadbent, J.R.; Cai, H.; Larsen, R.L.;

    2011-01-01

    of different strains to affect these characteristics can vary widely. Because these attributes are associated with enzymes involved in proteolysis or AA catabolism, we performed comparative genome hybridizations to a CNRZ 32 microarray to explore the distribution of genes encoding such enzymes across a bank...... of 38 Lb. helveticus strains, including 2 archival samples of CNRZ 32. Genes for peptidases and AA metabolism were highly conserved across the species, whereas those for cell envelope-associated proteinases varied widely. Some of the genetic differences that were detected may help explain...

  8. Effect of abomasal glucose infusion on splanchnic amino acid metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic AA metabolism. The experimental design was a split plot, with cow as the whole...... plot, treatment as the whole-plot factor and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: control or infusion of 1,500 g/d of glucose into the abomasum from the day of calving to 29 DIM....

  9. [Effect of mutations and modifications of amino acid residues on zinc-induced interaction of the metal-binding domain of β-amyloid with DNA].

    Science.gov (United States)

    Khmeleva, S A; Mezentsev, Y V; Kozin, S A; Mitkevich, V A; Medvedev, A E; Ivanov, A S; Bodoev, N V; Makarov, A A; Radko, S P

    2015-01-01

    Interaction of intranuclear β-amyloid with DNA is considered to be a plausible mechanism of Alzheimer's disease pathogenesis. The interaction of single- and double-stranded DNA with synthetic peptides was analyzed using surface plasmon resonance. The peptides represent the metal-binding domain of β-amyloid (amino acids 1-16) and its variants with chemical modifications and point substitutions of amino acid residues which are associated with enhanced neurotoxicity of β-amyloid in cell tests. It has been shown that the presence of zinc ions is necessary for the interaction of the peptides with DNA in solution. H6R substitution has remarkably reduced the ability of domain 1-16 to bind DNA. This is in accordance with the supposition that the coordination of a zinc ion by amino acid residues His6, Glu11, His13, and His14 of the β-amyloid metal-binding domain results in the occurrence of an anion-binding site responsible for the interaction of the domain with DNA. Zinc-induced dimerization and oligomerization of domain 1-16 associated with phosphorylation of Ser8 and the presence of unblocked amino- and carboxy-terminal groups have resulted in a decrease of peptide concentrations required for detection of the peptide-DNA interaction. The presence of multiple anion-binding sites on the dimers and oligomers is responsible for the enhancement of the peptide-DNA interaction. A substitution of the negatively charged residue Asp7 for the neutral residue Asn in close proximity to the anion-binding site of the domain 1-16 of Aβ facilitates the electrostatic interaction between this site and phosphates of a polynucleotide chain, which enhances zinc-induced binding to DNA.

  10. GlmS and NagB Regulate Amino Sugar Metabolism in Opposing Directions and Affect Streptococcus mutans Virulence

    Science.gov (United States)

    Kawada-Matsuo, Miki; Mazda, Yusuke; Oogai, Yuichi; Kajiya, Mikihito; Kawai, Toshihisa; Yamada, Sakuo; Miyawaki, Shouichi; Oho, Takahiko; Komatsuzawa, Hitoshi

    2012-01-01

    Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan) from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB) are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively. PMID:22438919

  11. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

    Directory of Open Access Journals (Sweden)

    Nengyi Zhang

    Full Text Available BACKGROUND: Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system. METHODOLOGY/PRINCIPAL FINDINGS: We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  12. Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids.

    Science.gov (United States)

    Zignego, Donald L; Hilmer, Jonathan K; June, Ronald K

    2015-12-16

    Chondrocytes are the sole cell type found in articular cartilage and are repeatedly subjected to mechanical loading in vivo. We hypothesized that physiological dynamic compression results in changes in energy metabolism to produce proteins for maintenance of the pericellular and extracellular matrices. The objective of this study was to develop an in-depth understanding for the short term (human chondrocytes harvested from femoral heads of osteoarthritic donors. Cell-seeded agarose constructs were randomly assigned to experimental groups, and dynamic compression was applied for 0, 15, or 30min. Following dynamic compression, metabolites were extracted and detected by HPLC-MS. Untargeted analyzes examined changes in global metabolomics profiles and targeted analysis examined the expression of specific metabolites related to central energy metabolism. We identified hundreds of metabolites that were regulated by applied compression, and we report the detection of 16 molecules not found in existing metabolite databases. We observed patient-specific mechanotransduction with aging dependence. Targeted studies found a transient increase in the ratio of NADP+ to NADPH and an initial decrease in the ratio of GDP to GTP, suggesting a flux of energy into the TCA cycle. By characterizing metabolomics profiles of primary chondrocytes in response to applied dynamic compression, this study provides insight into how OA chondrocytes respond to mechanical load. These results are consistent with increases in glycolytic energy utilization by mechanically induced signaling, and add substantial new data to a complex picture of how chondrocytes transduce mechanical loads.

  13. Fluorine-Tagged 5-Hydroxytryptophan to Investigate Amino Acid Metabolism In Vivo

    Directory of Open Access Journals (Sweden)

    Zofia E. Gagnon

    2010-01-01

    Full Text Available Auxin a plant growth hormone, has a metabolic pathway that includes molecules and enzymes like those in animal brains. In this study, tomato plant seedlings (Lycopersicon esculenta were used to investigate the fate of fluorine-tagged 5-hydroxytryptophan (PF-5-HTP being developed for fluorine spectroscopy and imaging. Seedlings were treated with high or low concentrations of 5-HTP or PF-5-HTP and compared with controls. Metabolites of the PF-5-HTP were quantified using a custom immunoassay for the tag. Serotonin (5-HT levels were measured with spectrofluorometry and thin-layer chromatography. Plants in treatment conditions had serotonin levels five to six times higher than controls. PF-5-HTP served as a precursor for serotonin in a biosynthetic pathway in this plant model, providing evidence for the bioavailability of the novel molecule. The increase in serotonin in plants grown in media culture supplemented with 5-HTP or PF-5-HTP might have useful applications in pharmacology.

  14. Fluorine-tagged 5-hydroxytryptophan to investigate amino Acid metabolism in vivo.

    Science.gov (United States)

    Gagnon, Zofia E; Dingman, Sherry; Thomas, Rhys N

    2010-01-01

    Auxin a plant growth hormone, has a metabolic pathway that includes molecules and enzymes like those in animal brains. In this study, tomato plant seedlings (Lycopersicon esculenta) were used to investigate the fate of fluorine-tagged 5-hydroxytryptophan (PF-5-HTP) being developed for fluorine spectroscopy and imaging. Seedlings were treated with high or low concentrations of 5-HTP or PF-5-HTP and compared with controls. Metabolites of the PF-5-HTP were quantified using a custom immunoassay for the tag. Serotonin (5-HT) levels were measured with spectrofluorometry and thin-layer chromatography. Plants in treatment conditions had serotonin levels five to six times higher than controls. PF-5-HTP served as a precursor for serotonin in a biosynthetic pathway in this plant model, providing evidence for the bioavailability of the novel molecule. The increase in serotonin in plants grown in media culture supplemented with 5-HTP or PF-5-HTP might have useful applications in pharmacology. PMID:22331995

  15. The Impact of Streptozotocin-induced Diabetes Mellitus on Cyclic Nucleotide Regulation of Skeletal Muscle Amino Acid Metabolism in the Rat

    OpenAIRE

    Garber, Alan J.

    1980-01-01

    The impact of diabetes on cyclic nucleotide-associated mechanisms regulating skeletal muscle protein and amino acid metabolism was assessed using epitrochlaris preparations from streptozotocin-induced diabetic rats. 1 nM epinephrine inhibited alanine and glutamine release from control preparations, but no inhibition was observed from diabetic preparations with

  16. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    NARCIS (Netherlands)

    Costas, B.; Aragao, C.; Ruiz-Jarabo, I.; Vargas-Chacoff, L.; Arjona, F.J.; Mancera, J.M.; Dinis, M.T.; Conceicao, L.E.

    2012-01-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26 degrees C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino aci

  17. Free amino acid formula: nitrogen utilization and metabolic effects in normal subjects.

    Science.gov (United States)

    Heller, P A; Shronts, E; Akrabawi, S; Heymsfield, S B

    1987-01-01

    A previous study indicated increased urea production and low nitrogen (N) retention on a free amino acid elemental formula (FAA; Vivonex-HN). The limitations of this earlier study were: irregular nitrogen absorption in the malabsorption patients, high nitrogen intake, and failure to match FAA to control formula (hydrolyzed casein; CAS; Criticare-HN) with respect to kcal/nitrogen. A more critical test of FAA quality was sought in the current study. Four healthy males received the minimal daily nitrogen requirements (0.6 g protein/kg) from either FAA or CAS in a 10-day balance study; a second balance on the alternate formula followed. Maintenance energy, minerals, and vitamins were supplied in each period. The results indicated a higher apparent nitrogen absorption (p less than 0.05) from FAA relative to CAS in the first 5 days of the balance, although these differences were no longer present in the remaining 5 days of the period. Urinary total nitrogen increased on FAA, most of which could be accounted for by urea nitrogen; urinary creatinine nitrogen, ammonia nitrogen, and uric acid nitrogen were nearly identical between formulas. The unmeasured fraction of urinary nitrogen was markedly diminished on FAA while the urea nitrogen to total nitrogen ratio was significantly increased (p less than 0.05) compared to CAS. During the initial 5 days of study nitrogen balance was lower on FAA than on CAS and this difference became significant during the last 5 days of the period (mean +/- SD for FAA = -0.42 +/- 0.59 g/D vs CAS = 0.98 +/- 0.30 g/day, p less than 0.001). Hyperglycinemia was consistently present during FAA infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3430685

  18. The effect of arsenic contamination on amino acids metabolism in Spinacia oleracea L.

    Science.gov (United States)

    Pavlík, Milan; Pavlíková, Daniela; Staszková, Ludmila; Neuberg, Marek; Kaliszová, Regina; Száková, Jirina; Tlustos, Pavel

    2010-09-01

    Changes of amino acid concentrations (proline, glutamate, asparagine, aspartate, alanine) and glutamate kinase activity (GKA) in plants under arsenic chronic stress reported here reveal their role in plant arsenic stress adaptation. Results of the pot experiment confirmed the toxic effect of arsenic at tested levels (As1=25 mg As kg(-1) soil, As2=50 mg As kg(-1) soil, As3=75 mg As kg(-1) soil) for spinach. Growing available arsenic contents in soil were associated with the strong inhibition of above-ground biomass and with the enhancement of As plant content. The changes of glutamate, asparagine, aspartate and proline levels in the plants showed strong linear dependences on arsenic concentration in plants (R2=0.60-0.90). Compared to the untreated control, concentrations of free proline and aspartate of As3 treatment were enhanced up to 381% and 162%, respectively. The significant changes of glutamate were observed on As2 and As3 treatments (increased level up to 188, i.e. 617%). Arsenic in plants was shown to be an inhibitor of glutamase kinase activity (R2=0.91). Inhibition of GKA resulted in an increase in the content of glutamate that is used in synthesis of phytochelatins in plant cells. Concentration of alanine did not have a confirmed linear dependence on arsenic concentration in plant (R2=0.05). The changes of its concentrations could be affected by changes of pH in plant cell or induction of alanine aminotransferase by hypoxia.

  19. The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons

    Directory of Open Access Journals (Sweden)

    Cezary Watala

    2013-11-01

    Full Text Available Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amidoamine (PAMAM dendrimers (G2, G3 and G4 have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia.

  20. Comparative Autoradiographic Study of the RNA and Protein Metabolism within the Various Tissues and Cells of the Mouse with Tritiated RNA Precursors and Labelled Amino Acids

    International Nuclear Information System (INIS)

    The first part of this report deals with autoradiographic studies of the incorporation of labelled amino acids into the various kinds of cells in mice and rats. The amount of the incorporation into the nucleus and into the cytoplasm was determined by grain counting. The results show that all nuclei within one cell-type and the nuclei of different cell-types have approximately the same incorporation rate per unit of nuclear volume. That means, that the amino acid incorporation within certain limits is generally proportional to the volume of a nucleus. Furthermore, the amino acid incorporation into the whole cytoplasm of the various examined cell-types was found to be 5 — 10 times greater than the nuclear incorporation. Therefore, the blackening distribution on autoradiographs with labelled amino acids can be understood by this simple incorporation scheme in connection with the varying size of the nuclear and cytoplasmatic volume of the different cell-types. On the other hand autoradiographic studies with tritiated cytidine and uridine have shown, that the incorporation of RNA precursors into the various tissues of mice and rats is proportional to that of amino acids. That suggests, that in all cells of the organism there exists a constant ratio between the size of protein metabolism and the size of (macromolecular) RNA metabolism. The protein metabolism in a cell is generally 20—30 times greater than the RNA metabolism. As in the case of amino acids incorporation the incorporation of tritiated cytidine into the nuclei of one cell-type and into the nuclei of different cell-types was found to be approximately proportional to the nuclear volume. (author)

  1. Long-term window of ischemic tolerance: An evolutionarily conserved form of metabolic plasticity regulated by epigenetic modifications?

    Science.gov (United States)

    Khoury, Nathalie; Koronowski, Kevin B.; Perez-Pinzon, Miguel A.

    2016-01-01

    In the absence of effective neuroprotective agents in the clinic, ischemic and pharmacological preconditioning are gaining increased interest in the field of cerebral ischemia. Our lab recently reported that resveratrol preconditioning affords tolerance against a focal cerebral ischemic insult in mice that can last for at least 14 days in vivo making it the longest window of ischemic tolerance discovered to date by a single administration of a pharmacological agent. The mechanism behind this novel extended window of ischemic tolerance remains elusive. In the below commentary we discuss potential mechanisms that could explain this novel extended window of ischemic tolerance in the context of previously identified windows and the known mechanisms behind them. We also draw parallels from the fields of hibernation and hypoxia-tolerance, which are chronic adaptations to severe conditions of hypoxia and ischemia known to be mediated by a form of metabolic depression. We also briefly discuss the importance of epigenetic modifications in maintaining this depressed state of metabolism.

  2. 2,4-D and IAA Amino Acid Conjugates Show Distinct Metabolism in Arabidopsis

    Science.gov (United States)

    Eyer, Luděk; Vain, Thomas; Pařízková, Barbora; Oklestkova, Jana; Barbez, Elke; Kozubíková, Hana; Pospíšil, Tomáš; Wierzbicka, Roksana; Kleine-Vehn, Jürgen; Fránek, Milan; Strnad, Miroslav; Robert, Stéphanie

    2016-01-01

    The herbicide 2,4-D exhibits an auxinic activity and therefore can be used as a synthetic and traceable analog to study auxin-related responses. Here we identified that not only exogenous 2,4-D but also its amide-linked metabolite 2,4-D-Glu displayed an inhibitory effect on plant growth via the TIR1/AFB auxin-mediated signaling pathway. To further investigate 2,4-D metabolite conversion, identity and activity, we have developed a novel purification procedure based on the combination of ion exchange and immuno-specific sorbents combined with a sensitive liquid chromatography-mass spectrometry method. In 2,4-D treated samples, 2,4-D-Glu and 2,4-D-Asp were detected at 100-fold lower concentrations compared to 2,4-D levels, showing that 2,4-D can be metabolized in the plant. Moreover, 2,4-D-Asp and 2,4-D-Glu were identified as reversible forms of 2,4-D homeostasis that can be converted to free 2,4-D. This work paves the way to new studies of auxin action in plant development. PMID:27434212

  3. Overcoming the Refractory Expression of Secreted Recombinant Proteins in Mammalian Cells through Modification of the Signal Peptide and Adjacent Amino Acids

    Science.gov (United States)

    Güler-Gane, Gülin; Kidd, Sara; Sridharan, Sudharsan; Vaughan, Tristan J.; Wilkinson, Trevor C. I.

    2016-01-01

    The expression and subsequent purification of mammalian recombinant proteins is of critical importance to many areas of biological science. To maintain the appropriate tertiary structure and post-translational modifications of such proteins, transient mammalian expression systems are often adopted. The successful utilisation of these systems is, however, not always forthcoming and some recombinant proteins prove refractory to expression in mammalian hosts. In this study we focussed on the role of different N-terminal signal peptides and residues immediately downstream, in influencing the level of secreted recombinant protein obtained from suspension HEK293 cells. Using secreted alkaline phosphatase (SEAP) as a model protein, we identified that the +1/+2 downstream residues flanking a heterologous signal peptide significantly affect secreted levels. By incorporating these findings we conducted a comparison of different signal peptide sequences and identified the most productive as secrecon, a computationally-designed sequence. Importantly, in the context of the secrecon signal peptide and SEAP, we also demonstrated a clear preference for specific amino acid residues at the +1 position (e.g. alanine), and a detrimental effect of others (cysteine, proline, tyrosine and glutamine). When proteins that naturally contain these “undesirable” residues at the +1 position were expressed with their native signal peptide, the heterologous secrecon signal peptide, or secrecon with an additional alanine at the +1 or +1 and +2 position, the level of expression differed significantly and in an unpredictable manner. For each protein, however, at least one of the panel of signal peptide/adjacent amino acid combinations enabled successful recombinant expression. In this study, we highlight the important interplay between a signal peptide and its adjacent amino acids in enabling protein expression, and we describe a strategy that could enable recombinant proteins that have so far

  4. Overcoming the Refractory Expression of Secreted Recombinant Proteins in Mammalian Cells through Modification of the Signal Peptide and Adjacent Amino Acids.

    Directory of Open Access Journals (Sweden)

    Gülin Güler-Gane

    Full Text Available The expression and subsequent purification of mammalian recombinant proteins is of critical importance to many areas of biological science. To maintain the appropriate tertiary structure and post-translational modifications of such proteins, transient mammalian expression systems are often adopted. The successful utilisation of these systems is, however, not always forthcoming and some recombinant proteins prove refractory to expression in mammalian hosts. In this study we focussed on the role of different N-terminal signal peptides and residues immediately downstream, in influencing the level of secreted recombinant protein obtained from suspension HEK293 cells. Using secreted alkaline phosphatase (SEAP as a model protein, we identified that the +1/+2 downstream residues flanking a heterologous signal peptide significantly affect secreted levels. By incorporating these findings we conducted a comparison of different signal peptide sequences and identified the most productive as secrecon, a computationally-designed sequence. Importantly, in the context of the secrecon signal peptide and SEAP, we also demonstrated a clear preference for specific amino acid residues at the +1 position (e.g. alanine, and a detrimental effect of others (cysteine, proline, tyrosine and glutamine. When proteins that naturally contain these "undesirable" residues at the +1 position were expressed with their native signal peptide, the heterologous secrecon signal peptide, or secrecon with an additional alanine at the +1 or +1 and +2 position, the level of expression differed significantly and in an unpredictable manner. For each protein, however, at least one of the panel of signal peptide/adjacent amino acid combinations enabled successful recombinant expression. In this study, we highlight the important interplay between a signal peptide and its adjacent amino acids in enabling protein expression, and we describe a strategy that could enable recombinant proteins that

  5. SIZ1-Dependent Post-Translational Modification by SUMO Modulates Sugar Signaling and Metabolism in Arabidopsis thaliana.

    Science.gov (United States)

    Castro, Pedro Humberto; Verde, Nuno; Lourenço, Tiago; Magalhães, Alexandre Papadopoulos; Tavares, Rui Manuel; Bejarano, Eduardo Rodríguez; Azevedo, Herlânder

    2015-12-01

    Post-translational modification mechanisms function as switches that mediate the balance between optimum growth and the response to environmental stimuli, by regulating the activity of key proteins. SUMO (small ubiquitin-like modifier) attachment, or sumoylation, is a post-translational modification that is essential for the plant stress response, also modulating hormonal circuits to co-ordinate developmental processes. The Arabidopsis SUMO E3 ligase SAP and Miz 1 (SIZ1) is the major SUMO conjugation enhancer in response to stress, and is implicated in several aspects of plant development. Here we report that known SUMO targets are over-represented in multiple carbohydrate-related proteins, suggesting a functional link between sumoylation and sugar metabolism and signaling in plants. We subsequently observed that SUMO-conjugated proteins accumulate in response to high doses of sugar in a SIZ1-dependent manner, and that the null siz1 mutant displays increased expression of sucrose and starch catabolic genes and shows reduced starch levels. We demonstrated that SIZ1 controls germination time and post-germination growth via osmotic and sugar-dependent signaling, respectively. Glucose was specifically linked to SUMO-sugar interplay, with high levels inducing root growth inhibition and aberrant root hair morphology in siz1. The use of sugar analogs and sugar marker gene expression analysis allowed us to implicate SIZ1 in a signaling pathway dependent on glucose metabolism, probably involving modulation of SNF1-related kinase 1 (SnRK1) activity.

  6. Potential use of carbon-11 labeled alpha-aminoisobutyric acid (AIB) as an in vivo tracer of amino acid uptake in differing metabolic states

    International Nuclear Information System (INIS)

    AIB has been used as a model amino acid for the evaluation of alanine-preferring amino acid transport. Hormonal factors and starvation alter the tissue distribution of amino acids, particularly in liver and muscle. With positron emission tomography and labeling of biochemical tracers with C-11, (t1/2=20.4 min), it is now possible to study amino acid kinetics in vivo using external imaging. In order to investigate the utility of C-11 AIB as an in vivo tracer of altered tissue metabolism, C-14 AIB was studied in groups of rats with either streptozotocin-induced diabetes, insulin-induced hypoglycemia or starvation. The data suggest an increased amino acid uptake in liver in starvation, an increased uptake in muscle in response to insulin and associated hypoglycemia and decreased transport in muscle in starvation, as seen by other investigators. These results suggest that C-11 AIB may be useful as an in vivo monitor of metabolic changes in body tissues

  7. Yuanhuapine-induced intestinal and hepatotoxicity were correlated with disturbance of amino acids, lipids, carbohydrate metabolism and gut microflora function: A rat urine metabonomic study.

    Science.gov (United States)

    Chen, Yanyan; Duan, Jin-Ao; Guo, Jianming; Shang, Erxin; Tang, Yuping; Qian, Yefei; Tao, Weiwei; Liu, Pei

    2016-07-15

    This research was designed to study metabonomic characteristics of the toxicity induced by yuanhuapine, a major bioactive diterpenoid in a well-known traditional Chinese medicine-Genkwa Flos. General observation, blood biochemistry and histopathological examination were used to reflect yuanhuapine-induced toxicity. Urine samples from rats in control and yuanhuapine treated rats were analyzed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Pattern recognition methods including principal components analysis (PCA), partial least-squared discriminant analysis (PLS-DA), orthogonal partial least-squared discriminant analysis (OPLS-DA) and computational system analysis were integrated to obtain comprehensive metabonomic profiling and pathways of the biological data sets. The results suggested that yuanhuapine could induce intestinal and liver damage. And 14 endogenous metabolites as biomarkers related to the amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora were significantly changed in the urine of yuanhuapine treated rats, which were firstly constructed the metabolomic feature profiling and metabolite interaction network of yuanhuapine-induced injury using pattern recognition methods and Ingenuity Pathway Analysis (IPA) approach. The present study showed that yuanhuapine-induced intestinal and hepatic toxicity were correlated with disturbance of amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora. PMID:26341729

  8. Ruminal protein metabolism and intestinal amino acid utilization as affected by dietary protein and carbohydrate sources in sheep.

    Science.gov (United States)

    Hussein, H S; Jordan, R M; Stern, M D

    1991-05-01

    Eight wether lambs fitted with ruminal, duodenal, and ileal cannulas were used in a replicated 4 x 4 Latin square design to study the effects of carbohydrate and protein sources on ruminal protein metabolism and carbohydrate fermentation and intestinal amino acid (AA) absorption. Treatments were arranged as a 2 x 2 factorial. Carbohydrate sources were corn and barley; protein sources were soybean meal (SBM) and fish meal (FM). Diets contained 15.5% CP, of which 40% was supplied by SBM or FM. Corn or barley provided 39% of dietary DM that contained equal amounts of grass hay and wheat straw. Fish meal diets produced a lower (P less than .05) ruminal NH3 concentration and resulted in less CP degradation and bacterial protein flow to the duodenum than did SBM diets. Replacing SBM with FM increased (P less than .05) ruminal digestion of all fiber fractions. In addition, cellulose and hemicellulose digestibilities in the rumen tended to increase (P greater than .05) when barley replaced corn in the FM diets. Carbohydrate x protein interactions (P less than .05) were observed for OM digestion in the rumen and AA absorption in the small intestine (percentage of AA entering); these interactions were highest for the barley-FM diet. These results suggest that feeding FM with barley, which is high in both degradable carbohydrate and protein, might benefit ruminants more than feeding FM with corn, which is high in degradable carbohydrate but relatively low in degradable protein. PMID:1648551

  9. THE DISTURBANCE OF METABOLISM OF THE AMINO ACIDS AS A CAUSATIVE FOR THE MENTAL RETARDATION-PHENYLKETONURIA

    Directory of Open Access Journals (Sweden)

    Jasmina IVANOVSKA

    2000-06-01

    Full Text Available PKU is the rare single-gene disease belonging to disturbance of metabolism of the amino acids, which in its own basics halved the mutated gene, whose leaning at the 12-chromosome charge for the synthesis of phenylalanine hydroxylase, turning on phenylalanine into tyrosine. Enzyme block usually leads to the accumulation of a toxic substrate and/or the deficient synthesis of a product needed for normal body function. In PKU there is a toxic accumulation of phenylalanine behind the deficient enzyme, phenylalanine hydrоxylase. The symptoms are: lighten hare, blue eyes, lithe pigmented skin, convulsion, mental retardation, low level of adrenalin caused for the lack of tyrosine, the urine have a specific smell of rats or gab.Inheritance of disease become in autosomal recessive way which always become possibility to stay hidden in the family and to inherit from knee to knee without manifestation of its own phenotype.The only therapy that successfully avoids the causes of this disease is phenylalanine-restricted diet. Today we have some affords for improvement of gene therapy, which can help us for determination to these disease. The success of the therapy depends from timing of the right detection also diagnostics all trough equivalent therapy which can successfully interrupt the new forms of mental retardation and other symptoms.

  10. Involvement of cellular metabolism in age-related LTP modifications in rat hippocampal slices.

    Science.gov (United States)

    Drulis-Fajdasz, Dominika; Wójtowicz, Tomasz; Wawrzyniak, Marcin; Wlodarczyk, Jakub; Mozrzymas, Jerzy W; Rakus, Dariusz

    2015-06-10

    Recent studies emphasized crucial role of astrocytic glycogen metabolism in regulation of synaptic transmission and plasticity in young animals. However, the interplay between age-related synaptic plasticity impairments and changes in energetic metabolism remains obscure. To address this issue, we investigated, in hippocampal slices of young (one month) and aged rats (20-22-months), the impact of glycogen degradation inhibition on LTP, mRNA expression for glycogen metabolism enzymes and morphology of dendritic spines. We show that, whereas in young hippocampi, inhibition of glycogen phosphorolysis disrupts the late phase of LTP in the Schaffer collateral-CA1 pathway, in aged rats, blockade of glycogen phosphorylase tends to enhance it. Gene expression for key energy metabolism enzymes, such as glycogen synthase and phosphorylase and glutamine synthetase showed marked differences between young and aged groups and changes in expression of these enzymes preceded plasticity phenomena. Interestingly, in the aged group, a prominent expression of these enzymes was found also in neurons. Concluding, we show that LTP in the considered pathway is differentially modulated by metabolic processes in young and aging animals, indicating a novel venue of studies aiming at preventing cognitive decline during aging. PMID:26101857

  11. Effects of Denaturation and Amino Acid Modification on Fluorescence Spectrum and Hemagglutinating Activity of Hericium erinaceum Lectin

    Institute of Scientific and Technical Information of China (English)

    Meng GONG; Jie AN; Hong-Zhou LU; Chuan-Fang WU; Yi-Jin LI; Jing-Qiu CHENG; Jin-Ku BAO

    2004-01-01

    A sialic acid-binding lectin (Hericium erinaceum lectin, HEL), isolated from fresh fruiting bodies of Hericium erinaceum, was treated with various temperature and pH to investigate its fluorescencespectra and hemagglutinating activity. It was found that the hemagglutinating activity of HEL was relatively steady below 60℃ and at pH from 6 to 11, and the change of hemagglutinating activity was relative to thechange of hydrophobic areas where tryptophan residues located. In fluorescence quenching study of HEL byacrylamide and K1, it was indicated that nearly all the tryptophan residues of HEL located on the surface ofthe molecule, and most of them were in hydrophobic areas or negatively charged areas. Chemical modifica-tion of HEL proved that there were about twelve tryptophan residues in a HEL molecule and all of them werelocated on the surface or in the shallow groove of the molecule, and eight of them were essential for hemag-glutinating activity; aspartic acid or glutamic acid residues were involved in maintaining the crucial confor-mation of activity center and made great contribution to the hemagglutinating activity of HEL, but they could not touch the sialic acid molecule directly; tyrosine residues also played a role in the hemagglutinating activ-ity of HEL; while arginine, serine, threonine, histidine residues had no effect on the hemagglutinating activity of HEL.

  12. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    International Nuclear Information System (INIS)

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  13. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    Science.gov (United States)

    Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

    2008-11-01

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  14. Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells.

    Science.gov (United States)

    Reisz, Julie A; Wither, Matthew J; Dzieciatkowska, Monika; Nemkov, Travis; Issaian, Aaron; Yoshida, Tatsuro; Dunham, Andrew J; Hill, Ryan C; Hansen, Kirk C; D'Alessandro, Angelo

    2016-09-22

    Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) plays a key regulatory function in glucose oxidation by mediating fluxes through glycolysis or the pentose phosphate pathway (PPP) in an oxidative stress-dependent fashion. Previous studies documented metabolic reprogramming in stored red blood cells (RBCs) and oxidation of GAPDH at functional residues upon exposure to pro-oxidants diamide and H2O2 Here we hypothesize that routine storage of erythrocyte concentrates promotes metabolic modulation of stored RBCs by targeting functional thiol residues of GAPDH. Progressive increases in PPP/glycolysis ratios were determined via metabolic flux analysis after spiking (13)C1,2,3-glucose in erythrocyte concentrates stored in Additive Solution-3 under blood bank conditions for up to 42 days. Proteomics analyses revealed a storage-dependent oxidation of GAPDH at functional Cys152, 156, 247, and His179. Activity loss by oxidation occurred with increasing storage duration and was progressively irreversible. Irreversibly oxidized GAPDH accumulated in stored erythrocyte membranes and supernatants through storage day 42. By combining state-of-the-art ultra-high-pressure liquid chromatography-mass spectrometry metabolic flux analysis with redox and switch-tag proteomics, we identify for the first time ex vivo functionally relevant reversible and irreversible (sulfinic acid; Cys to dehydroalanine) oxidations of GAPDH without exogenous supplementation of excess pro-oxidant compounds in clinically relevant blood products. Oxidative and metabolic lesions, exacerbated by storage under hyperoxic conditions, were ameliorated by hypoxic storage. Storage-dependent reversible oxidation of GAPDH represents a mechanistic adaptation in stored erythrocytes to promote PPP activation and generate reducing equivalents. Removal of irreversibly oxidized, functionally compromised GAPDH identifies enhanced vesiculation as a self-protective mechanism in ex vivo aging erythrocytes.

  15. Potential protein post-translational modifications and find potential single amino acid substitutions in hepatitis B large envelope protein Posibles modificaciones postranslacionales y sustituciones de un solo aminoácido en la proteína grande de la superficie del virus de la hepatitis B

    OpenAIRE

    V Wiwanitkit

    2008-01-01

    Post-translational modifications of proteins control many biological processes. This is also important process in virus including hepatitis B. However, there is no in-depth study on the whole hepatitis B virus large envelope protein. In this work, potential protein post-translational modifications in hepatitis B virus large envelope protein were determined by a standard bioinformatics technique. Furthermore, potential single amino acid substitutions in hepatitis B large envelope protein were ...

  16. GC-MS/MS survey of collision-induced dissociation of tert-butyldimethylsilyl-derivatized amino acids and its application to (13)C-metabolic flux analysis of Escherichia coli central metabolism.

    Science.gov (United States)

    Okahashi, Nobuyuki; Kawana, Shuichi; Iida, Junko; Shimizu, Hiroshi; Matsuda, Fumio

    2016-09-01

    Stable isotope labeling experiments using mass spectrometry have been employed to investigate carbon flow levels (metabolic flux) in mammalian, plant, and microbial cells. To achieve a more precise (13)C-metabolic flux analysis ((13)C-MFA), novel fragmentations of tert-butyldimethylsilyl (TBDMS)-amino acids were investigated by gas chromatography-tandem mass spectrometry (GC-MS/MS). The product ion scan analyses of 15 TBDMS-amino acids revealed 24 novel fragment ions. The amino acid-derived carbons included in the five fragment ions were identified by the analyses of (13)C-labeled authentic standards. The identification of the fragment ion at m/z 170 indicated that the isotopic abundance of S-methyl carbon in methionine could be determined from the cleavage of C5 in the precursor of [M-159](+) (m/z 218). It was also confirmed that the precision of (13)C-MFA in Escherichia coli central carbon metabolism could be improved by introducing (13)C-labeling data derived from novel fragmentations. Graphical Abstract Novel collision-induced dissociation fragmentations of tert-butyldimethylsilyl amino acids were investigated and identified by GC-MS/MS.

  17. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community

    OpenAIRE

    Hirosuke Sugahara; Toshitaka Odamaki; Shinji Fukuda; Tamotsu Kato; Jin-zhong Xiao; Fumiaki Abe; Jun Kikuchi; Hiroshi Ohno

    2015-01-01

    Probiotics are well known as health-promoting agents that modulate intestinal microbiota. However, the molecular mechanisms underlying this effect remain unclear. Using gnotobiotic mice harboring 15 strains of predominant human gut-derived microbiota (HGM), we investigated the effects of Bifidobacterium longum BB536 (BB536-HGM) supplementation on the gut luminal metabolism. Nuclear magnetic resonance (NMR)-based metabolomics showed significantly increased fecal levels of pimelate, a precursor...

  18. Probiotic Bifidobacterium longum alters gut luminal metabolism through modification of the gut microbial community.

    Science.gov (United States)

    Sugahara, Hirosuke; Odamaki, Toshitaka; Fukuda, Shinji; Kato, Tamotsu; Xiao, Jin-zhong; Abe, Fumiaki; Kikuchi, Jun; Ohno, Hiroshi

    2015-01-01

    Probiotics are well known as health-promoting agents that modulate intestinal microbiota. However, the molecular mechanisms underlying this effect remain unclear. Using gnotobiotic mice harboring 15 strains of predominant human gut-derived microbiota (HGM), we investigated the effects of Bifidobacterium longum BB536 (BB536-HGM) supplementation on the gut luminal metabolism. Nuclear magnetic resonance (NMR)-based metabolomics showed significantly increased fecal levels of pimelate, a precursor of biotin, and butyrate in the BB536-HGM group. In addition, the bioassay revealed significantly elevated fecal levels of biotin in the BB536-HGM group. Metatranscriptomic analysis of fecal microbiota followed by an in vitro bioassay indicated that the elevated biotin level was due to an alteration in metabolism related to biotin synthesis by Bacteroides caccae in this mouse model. Furthermore, the proportion of Eubacterium rectale, a butyrate producer, was significantly higher in the BB536-HGM group than in the group without B. longum BB536 supplementation. Our findings help to elucidate the molecular basis underlying the effect of B. longum BB536 on the gut luminal metabolism through its interactions with the microbial community.

  19. Effects of Various Dietary Amino Acid Preparations for Phenylketonuric Patients on the Metabolic Profiles along with Postprandial Insulin and Ghrelin Responses

    OpenAIRE

    Weigel, Corina; Rauh, Manfred; Kiener, C.; Rascher, Wolfgang; Knerr, Ina

    2013-01-01

    Aim: We investigated the metabolic profiles along with insulin and ghrelin responses following ingestion of various amino acid (AA) substitutes commonly used in the treatment of phenylketonuria to study the effects of added macronutrients. Methods: Twenty healthy and 6 phenylketonuric adults ingested AA mixtures with or without carbohydrates and fat (Anamix, Easiphen, or p-am 3; 0.35 g AA/kg body weight); milk powder shakes were used for control purposes. Serum AA, glucose, urea, insulin, and...

  20. Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

    Directory of Open Access Journals (Sweden)

    Jeremy G Warren

    Full Text Available Polygalacturonases (EC 3.2.1.15 catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485, and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/LK motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different

  1. Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

    Science.gov (United States)

    Warren, Jeremy G; Lincoln, James E; Kirkpatrick, Bruce C

    2015-01-01

    Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or

  2. The rice R2R3-MYB transcription factor OsMYB55 is involved in the tolerance to high temperature and modulates amino acid metabolism.

    Directory of Open Access Journals (Sweden)

    Ashraf El-Kereamy

    Full Text Available Temperatures higher than the optimum negatively affects plant growth and development. Tolerance to high temperature is a complex process that involves several pathways. Understanding this process, especially in crops such as rice, is essential to prepare for predicted climate changes due to global warming. Here, we show that OsMYB55 is induced by high temperature and overexpression of OsMYB55 resulted in improved plant growth under high temperature and decreased the negative effect of high temperature on grain yield. Transcriptome analysis revealed an increase in expression of several genes involved in amino acids metabolism. We demonstrate that OsMYB55 binds to the promoter regions of target genes and directly activates expression of some of those genes including glutamine synthetase (OsGS1;2 glutamine amidotransferase (GAT1 and glutamate decarboxylase 3 (GAD3. OsMYB55 overexpression resulted in an increase in total amino acid content and of the individual amino acids produced by the activation of the above mentioned genes and known for their roles in stress tolerance, namely L-glutamic acid, GABA and arginine especially under high temperature condition. In conclusion, overexpression of OsMYB55 improves rice plant tolerance to high temperature, and this high tolerance is associated with enhanced amino acid metabolism through transcription activation.

  3. Studies on the protein and amino acid metabolism of laying hens using 15N-labelled casein. 8

    International Nuclear Information System (INIS)

    Four colostomized Leghorn hens were fed, during 6 days, 15N-labelled casein as sole protein source. Two animals were slaughtered 48 hours, the other two 144 hours after the last 15N-application. The share of TCE-soluble N in total N averaged 16% for the body parts analysed, i.e. meat, bone, liver, kidneys, oviducts, residual viscera and other. The variation of the lysine, histidine and arginine levels in the body parts ranged from 3.6 to 7.9 g, 1.1 to 3.7 g and 6.4 to 7.4 g in 16.7 g hydrolysate N, respectively. Except for feathers, the analysed body parts contained an excess amount of heavy nitrogen. The degree of labelling was found to depend on the time of slaughtering after the tracer application. In the liver and in the oviduct being metabolically active organs, the 15N-excess in the total N fraction decreased by 45% between the 2nd and the 6th days after 15N-feeding, whilst in the meat it went down by 20%. The decline of the 15N-concentration in the TCE-soluble N compounds was faster than in the total N-fraction. Out of the body samples analysed, the lysine of the liver having 0.26 atom% 15N-excess was found to be more strongly labelled in hens 1 and 2. The amino acid arginine reached about the same level of labelling, the 15N-frequency of histidine being the lowest. (author)

  4. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... build up in the body. For these people, eating foods that are high in protein can cause serious health problems and, sometimes, death. People with these kinds of disorders may need to limit or avoid certain foods ...

  5. Branched-chain amino acid interactions with reference to amino acid requirements in adult men: Valine metabolism at different leucine intakes

    International Nuclear Information System (INIS)

    The authors explored whether the oxidation of valine and by implication the physiological requirement for this amino acid are affected by changes in leucine intake over a physiological range. Six young adult men received, in random order, four L-amino acid-based diets for 5 d supplying either 20 or 10 mg valine.kg body wt-1.d-1, each in combination with 80 or 40 mg leucine.kg-1.d-1. On day 6 subjects were studied with an 8-h continuous intravenous infusion of [1-13C]valine (and [2H3]leucine) to determine valine oxidation in the fasted state (first 3 h) and fed state (last 5 h). Valine oxidation in the fasted state was similar among all diets but was lower (P less than 0.05) in the fed state for the 10 vs 20 mg valine.kg-1.d-1 intake. Leucine intake did not affect valine oxidation. Mean daily valine balance approximated +1.3 mg.kg-1.d-1 for the 20-mg intake and -1.6 mg.kg-1.d-1 for the 10-mg intake. These findings support our previously suggested mean valine requirement estimate of approximately 20 mg.kg-1.d-1

  6. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    Science.gov (United States)

    Costas, Benjamín; Aragão, Cláudia; Ruiz-Jarabo, Ignacio; Vargas-Chacoff, Luis; Arjona, Francisco J; Mancera, Juan M; Dinis, Maria T; Conceição, Luís E C

    2012-07-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26°C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino acid changes during thermal acclimation. Senegalese sole maintained at 18°C were acclimated to either cold (12°C) or warm (26°C) environmental temperatures for 21 days. Fish maintained at 18°C served as control. Plasma concentrations of cortisol, glucose, lactate, triglycerides, proteins, and free amino acids were assessed. Cold acclimation influenced interrenal responses of sole by increasing cortisol release. Moreover, plasma glucose and lactate concentrations increased linearly with temperature, presumably reflecting a higher metabolic activity of sole acclimated to 26°C. Acclimation temperature affected more drastically plasma concentrations of dispensable than that of indispensable amino acids, and different acclimation temperatures induced different responses. Asparagine, glutamine and ornithine seem to be of particular importance for ammonia detoxification mechanisms, synthesis of triglycerides that may be used during homeoviscous adaptation and, to a lesser extent, as energetic substrates in specimens acclimated to 12°C. When sole is acclimated to 26°C taurine, glutamate, GABA and glycine increased, which may suggest important roles as antioxidant defences, in osmoregulatory processes and/or for energetic purposes at this thermal regimen. In conclusion, acclimation to different environmental temperatures induces several metabolic changes in Senegalese sole, suggesting that amino acids may be important for thermal acclimation. PMID:21947601

  7. Effects of an eight-week supervised, structured lifestyle modification programme on anthropometric, metabolic and cardiovascular risk factors in severely obese adults.

    LENUS (Irish Health Repository)

    Crowe, Catherine

    2015-08-01

    Lifestyle modification is fundamental to obesity treatment, but few studies have described the effects of structured lifestyle programmes specifically in bariatric patients. We sought to describe changes in anthropometric and metabolic characteristics in a cohort of bariatric patients after participation in a nurse-led, structured lifestyle programme.

  8. Nutritional value of protein hydrolysis products (oligopeptides and free amino acids) as a consequence of absorption and metabolism kinetics

    Science.gov (United States)

    Rerat, A.

    1995-01-01

    When pigs were submitted to duodenal infusion of solutions containing a large percentage of small peptides (PEP) or free amino acids with the same pattern (AAL) amino acids appear in the portal blood more rapidly and more uniformly after infusion of PEP then after infusion of AAL, with the notable exception of methionine for which the opposite was true. These differences were lowered when a carbohydrate (maltose dextrin) was present in the solution, but nevertheless remained significant for the first hour after the infusion. The long-term (8-hour) uptake of free amino acids into the liver and the peripheral tissues differed in profile according to the nature of the duodenal infusion. Peripheral uptake was appreciably less well balanced after infusion of free amino acids (deficiency of threonine and phenylalanine) than after infusion of small peptides (deficiency of methionine). Accordingly, in the rat, under conditions of discontinuous enteral nutrition the mixture of small peptides was of greater nutritive value than the mixture of free amino acids. It thus appears that the absorption kinetics which results in important variations in the temporal distribution of free amino acids in the tissues may be at the origin of transitory imbalances in tissue amino acid uptake, and as a result of a lower nutritive value.

  9. Diet modification and its influence on metabolic and related pathological alterations in the SHR/NDmcr-cp rat, an animal model of the metabolic syndrome.

    Science.gov (United States)

    Kawai, Kouji; Sakairi, Tetsuya; Harada, Shuichi; Shinozuka, Junko; Ide, Mika; Sato, Hiroko; Tanaka, Masaharu; Toriumi, Wataru; Kume, Eisuke

    2012-05-01

    SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks. SHR/NDcp rats receiving the normal diet displayed obesity, hypertension, hyperlipidemia, and mild elevation of blood glucose and HbA1c levels. Urinary glucose excretion was noted in only 1 out of 6 animals. Histologically, macro- and micro-vesicular steatosis in the liver, glomerular and tubular damages in the kidney and islet hyperplasia mainly of beta cells in the pancreas were characteristically noted. In SHR/NDcp rats fed the diabetogenic diet, obesity was more severe, with higher blood glucose and HbA1c levels, increased numbers of animals with urinary glucose excretion, and more pronounced hepatic steatosis and renal tubular changes. However, elevation of blood glucose levels and urinary glucose excretion proved transient. These observations indicate that the diabetic state and associated histopathological alterations in SHR/NDcp rats are exacerbated by feeding a diabetogenic diet, but the effects are limited. Elevated islet function with compensative insulin secretion might be related to amelioration of the hyperglycemic state. Further diet modification could be needed to induce a more prominent and persistent diabetic state in SHR/NDcp rats.

  10. Proteomic Dissection of Endosperm Starch Granule Associated Proteins Reveals a Network Coordinating Starch Biosynthesis and Amino Acid Metabolism and Glycolysis in Rice Endosperms

    Science.gov (United States)

    Yu, Huatao; Wang, Tai

    2016-01-01

    Starch biosynthesis and starch granule packaging in cereal endosperms involve a coordinated action of starch biosynthesis enzymes and coordination with other metabolisms. Because directly binding to starch granules, starch granule-associated proteins (SGAPs) are essential to understand the underlying mechanisms, however the information on SGAPs remains largely unknown. Here, we dissected developmentally changed SGAPs from developing rice endosperms from 10 to 20 days after flowering (DAF). Starch granule packaging was not completed at 10 DAF, and was finished in the central endosperm at 15 DAF and in the whole endosperm at 20 DAF. Proteomic analysis with two-dimensional differential in-gel electrophoresis and mass spectrometry revealed 115 developmentally changed SGAPs, representing 37 unique proteins. 65% of the unique proteins had isoforms. 39% of the identified SGAPs were involved in starch biosynthesis with main functions in polyglucan elongation and granule structure trimming. Almost all proteins involved in starch biosynthesis, amino acid biosynthesis, glycolysis, protein folding, and PPDK pathways increased abundance as the endosperm developed, and were predicted in an interaction network. The network represents an important mechanism to orchestrate carbon partitioning among starch biosynthesis, amino acid biosynthesis and glycolysis for efficient starch and protein storage. These results provide novel insights into mechanisms of starch biosynthesis and its coordination with amino acid metabolisms and glycolysis in cereal endosperms. PMID:27252723

  11. Modifications of xyloglucan metabolism in azuki bean epicotyls under hypergravity conditions

    Science.gov (United States)

    Soga, Kouichi; Arai, Kuninori; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Hoson, Takayuki

    We examined the effects of hypergravity on both the synthesis and the depolymerization processes of xyloglucan metabolisms. Azuki bean cuttings were incubated with [6-3H]-L-fucose, and the levels and the molecular size of synthesized xyloglucans were investigated in the upper growing regions of epicotyls. The amounts of radioactivity incorporated into xyloglucan fraction increased during incubation, irrespective of the gravity conditions. 3H-Xyloglucans were eluted in the higher molecular mass regions than xyloglucans already present in the cell wall. Hypergravity at 300 g did not influence the molecular size of newly deposited xyloglucans. Thus, the process of xyloglucan synthesis was not modified by the gravitational force. On the other hand, 3H-xyloglucans obtained from epicotyls grown at 1 g were shifted to the low molecular mass regions during the incubation period, which was inhibited by hypergravity. These results indicate that xyloglucans were deposited into the cell wall as large molecules but they were then depolymerized in the cell wall, and that the inhibition of the depolymerization is mainly responsible for the increase in the molecular size of xyloglucans under hypergravity conditions.

  12. Effects of supplementation with 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester on splanchnic amino acid metabolism and essential amino acid mobilization in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Dalbach, Kristine Foged; Larsen, Mogens; Raun, Birgitte Marie Løvendahl;

    2011-01-01

    The present study aimed to investigate the effects of 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) supplementation on splanchnic AA metabolism, essential AA (EAA) mobilization, and plasma AA status in postpartum transition dairy cows. The EAA mobilization was calculated by differ...... the first 29 DIM. Extra-splanchnic EAA mobilization can be crucial to sustain milk protein yield in the postpartum transition period and HMBi is a fast-working Met source that can improve Met status of postpartum transition cows.......The present study aimed to investigate the effects of 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) supplementation on splanchnic AA metabolism, essential AA (EAA) mobilization, and plasma AA status in postpartum transition dairy cows. The EAA mobilization was calculated...... by difference: EAA excretion in milk protein − net portal absorption of EAA or net splanchnic release of EAA. Eight Holstein cows fitted with permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery in the dry period preceding second parturition were used...

  13. Ethylene suppresses tomato (Solanum lycopersicum) fruit set through modification of gibberellin metabolism.

    Science.gov (United States)

    Shinozaki, Yoshihito; Hao, Shuhei; Kojima, Mikiko; Sakakibara, Hitoshi; Ozeki-Iida, Yuko; Zheng, Yi; Fei, Zhangjun; Zhong, Silin; Giovannoni, James J; Rose, Jocelyn K C; Okabe, Yoshihiro; Heta, Yumi; Ezura, Hiroshi; Ariizumi, Tohru

    2015-07-01

    Fruit set in angiosperms marks the transition from flowering to fruit production and a commitment to seed dispersal. Studies with Solanum lycopersicum (tomato) fruit have shown that pollination and subsequent fertilization induce the biosynthesis of several hormones, including auxin and gibberellins (GAs), which stimulate fruit set. Circumstantial evidence suggests that the gaseous hormone ethylene may also influence fruit set, but this has yet to be substantiated with molecular or mechanistic data. Here, we examined fruit set at the biochemical and genetic levels, using hormone and inhibitor treatments, and mutants that affect auxin or ethylene signaling. The expression of system-1 ethylene biosynthetic genes and the production of ethylene decreased during pollination-dependent fruit set in wild-type tomato and during pollination-independent fruit set in the auxin hypersensitive mutant iaa9-3. Blocking ethylene perception in emasculated flowers, using either the ethylene-insensitive Sletr1-1 mutation or 1-methylcyclopropene (1-MCP), resulted in elongated parthenocarpic fruit and increased cell expansion, whereas simultaneous treatment with the GA biosynthesis inhibitor paclobutrazol (PAC) inhibited parthenocarpy. Additionally, the application of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to pollinated ovaries reduced fruit set. Furthermore, Sletr1-1 parthenocarpic fruits did not exhibit increased auxin accumulation, but rather had elevated levels of bioactive GAs, most likely reflecting an increase in transcripts encoding the GA-biosynthetic enzyme SlGA20ox3, as well as a reduction in the levels of transcripts encoding the GA-inactivating enzymes SlGA2ox4 and SlGA2ox5. Taken together, our results suggest that ethylene plays a role in tomato fruit set by suppressing GA metabolism. PMID:25996898

  14. Pea aphid promotes amino acid metabolism both in Medicago truncatula and bacteriocytes to favor aphid population growth under elevated CO2.

    Science.gov (United States)

    Guo, Huijuan; Sun, Yucheng; Li, Yuefei; Tong, Bin; Harris, Marvin; Zhu-Salzman, Keyan; Ge, Feng

    2013-10-01

    Rising atmospheric CO(2) levels can dilute the nitrogen (N) resource in plant tissue, which is disadvantageous to many herbivorous insects. Aphids appear to be an exception that warrants further study. The effects of elevated CO(2) (750 ppm vs. 390 ppm) were evaluated on N assimilation and transamination by two Medicago truncatula genotypes, a N-fixing-deficient mutant (dnf1) and its wild-type control (Jemalong), with and without pea aphid (Acyrthosiphon pisum) infestation. Elevated CO(2) increased population abundance and feeding efficiency of aphids fed on Jemalong, but reduced those on dnf1. Without aphid infestation, elevated CO(2) increased photosynthetic rate, chlorophyll content, nodule number, biomass, and pod number for Jemalong, but only increased pod number and chlorophyll content for dnf1. Furthermore, aphid infested Jemalong plants had enhanced activities of N assimilation-related enzymes (glutamine synthetase, Glutamate synthase) and transamination-related enzymes (glutamate oxalate transaminase, glutamine phenylpyruvate transaminase), which presumably increased amino acid concentration in leaves and phloem sap under elevated CO(2). In contrast, aphid infested dnf1 plants had decreased activities of N assimilation-related enzymes and transmination-related enzymes and amino acid concentrations under elevated CO(2). Furthermore, elevated CO(2) up-regulated expression of genes relevant to amino acid metabolism in bacteriocytes of aphids associated with Jemalong, but down-regulated those associated with dnf1. Our results suggest that pea aphids actively elicit host responses that promote amino acid metabolism in both the host plant and in its bacteriocytes to favor the population growth of the aphid under elevated CO(2).

  15. Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes

    OpenAIRE

    Francisco Javier Ruiz-Ojeda; Carolina Gomez-Llorente; Concepción María Aguilera; Angel Gil; Azahara Iris Rupérez

    2016-01-01

    Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and inc...

  16. Effect of Carbon and Nitrogen Availability on Metabolism of Amino Acids in Germinating Spores of Arbuscular Mycorrhizal Fungi

    Institute of Scientific and Technical Information of China (English)

    JIN Hai-Ru; JIANG Dong-Hua; ZHANG Ping-Hua

    2011-01-01

    The effects of carbon (C) and nitrogen (N) sources on N utilization and biosynthesis of amino acids were examined in the germinating spores of the arbuscular mycorrhizal (AM) fungus Glomus intraradices Schenck & Smith after exposure to various N substrates,CO2,glucose,and/or root exudates.The N uptake and de novo biosynthesis of amino acids were analyzed using stable isotopic labeling with mass spectrometric detection.High-performance liquid chromatography-based analysis was used to measure amino acid levels.In the absence of exogenous N sources and in the presence of 25 mL L-1 CO2,the germinating AM fungal spores utilized internal N storage as well as C skeletons derived from the degradation of storage lipids to biosynthesize the free amino acids,in which serine and glycine were produced predominantly.The concentrations of internal amino acids increased gradually as the germination time increased from 0 to 1 or 2 weeks.However,asparagine and glutamine declined to the low levels; both degraded to provide the biosynthesis of other amino acids with C and N donors.The availability of exogenous inorganic N (ammonium and nitrate) and organic N (urea,arginine,and glutamine) to the AM fungal spores using only CO2 for germination generated more than 5 times more internal free amino acids than those in the absence of exogenous N.A supply of exogenous nitrate to the AM fungal spores with only CO2 gave rise to more than 10 times more asparagine than that without exogenous N.In contrast,the extra supply of exogenous glucose to the AM fungal spores generated a significant enhancement in the uptake of exogenous N sources,with more than 3 times more free amino acids being produced than those supplied with only exogenous CO2.Meanwhile,arginine was the most abundant free amino acid produced and it was incorporated into the proteins of AM fungal spores to serve as an N storage compound.

  17. Amino Acid Metabolism of Thermoanaerobacter Strain AK90: The Role of Electron-Scavenging Systems in End Product Formation

    Directory of Open Access Journals (Sweden)

    Sean Michael Scully

    2015-01-01

    Full Text Available The catabolism of the 20 amino acids by Thermoanaerobacter strain AK90 (KR007667 was investigated under three different conditions: as single amino acids without an electron-scavenging system, in the presence of thiosulfate, and in coculture with a hydrogenotrophic methanogen. The strain degraded only serine without an alternative electron acceptor but degraded 11 amino acids (alanine, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tyrosine, and valine under both of the electron-scavenging systems investigated. Acetate was the dominant end product from alanine, cysteine, lysine, serine, and threonine under electron-scavenging conditions. The branched-chain amino acids, isoleucine, leucine, and valine, were degraded to their corresponding fatty acids under methanogenic conditions and to a mixture of their corresponding fatty acids and alcohols in the presence of thiosulfate. The partial pressure of hydrogen seems to be of importance for the branched-chain alcohol formation. This was suggested by low but detectable hydrogen concentrations at the end of cultivation on the branched-chain amino acid in the presence of thiosulfate but not when cocultured with the methanogen. A more detailed examination of the role of thiosulfate as an electron acceptor was performed with Thermoanaerobacter ethanolicus (DSM 2246 and Thermoanaerobacter brockii (DSM 1457.

  18. Has a mixture of amino acids and micronutrients influence on glucose metabolism and dietary fatty acid pattern in chronic psychosocially stressed persons? A pilot study.

    Science.gov (United States)

    Bitterlich, Norman; Chaborski, Katrin; Parsi, Elke; Rösler, Daniela; Metzner, Christine

    2016-01-01

    Brain food, e.g. L-tryptophan, antioxidative substances, B vitamins and magnesium are thought to be beneficial for obesity, inflammation and insulin resistance. In the present pilot study we hypothesised that a specific amino acid mixture with micronutrients improves the cardiometabolic situation of chronically stressed persons. Cardiovascular and metabolic parameters were analysed as per protocol in 32 patients. Chronic stress disorders in the same patients were assessed by a psychological neurological questionnaire (PNF). After dietary intervention a reduction of the fasting serum insulin concentrations occurred in the treatment group. An association was found between PNF values, insulin concentrations at baseline and an insulin reduction after 12 weeks. The results support the use of our specific dietary supplement for improved stress management and a decrease in metabolic dysfunction. PMID:26878772

  19. [Clinical picture of Hartnup disease. Without urine amino acids or any other identified metabolic disorder (a new entity)].

    Science.gov (United States)

    Da Gloria, E R; Assunção, J G; Costa, M A

    1990-01-01

    Harthnup disease clinical picture without aminoaciduria or other identified metabolic disturb (New entity?). The authors present a patient with clinical picture superposed to the Hartnup disease's, a rare, autosomic and recessive metabolic disturbance, characterized by typical aminoaciduria consequent to tryptophan and other neutral aminoacids defective transport by jejunal mucous membrane and renal tubules, clinically expressed by photosensitive pellagra-like dermatitis, mental retardation and intermittent cerebellar ataxia. The laboratorial results did not confirm Hartnup aminoaciduria nor other identified metabolic change that justify his clinical manifestations. PMID:2077308

  20. CypD(-/-) hearts have altered levels of proteins involved in Krebs cycle, branch chain amino acid degradation and pyruvate metabolism.

    Science.gov (United States)

    Menazza, Sara; Wong, Renee; Nguyen, Tiffany; Wang, Guanghui; Gucek, Marjan; Murphy, Elizabeth

    2013-03-01

    Cyclophilin D (CypD) is a mitochondrial chaperone that has been shown to regulate the mitochondrial permeability transition pore (MPTP). MPTP opening is a major determinant of mitochondrial dysfunction and cardiomyocyte death during ischemia/reperfusion (I/R) injury. Mice lacking CypD have been widely used to study regulation of the MPTP, and it has been shown recently that genetic depletion of CypD correlates with elevated levels of mitochondrial Ca(2+). The present study aimed to characterize the metabolic changes in CypD(-/-) hearts. Initially, we used a proteomics approach to examine protein changes in CypD(-/-) mice. Using pathway analysis, we found that CypD(-/-) hearts have alterations in branched chain amino acid metabolism, pyruvate metabolism and the Krebs cycle. We tested whether these metabolic changes were due to inhibition of electron transfer from these metabolic pathways into the electron transport chain. As we found decreased levels of succinate dehydrogenase and electron transfer flavoprotein in the proteomics analysis, we examined whether activities of these enzymes might be altered. However, we found no alterations in their activities. The proteomics study also showed a 23% decrease in carnitine-palmitoyltransferase 1 (CPT1), which prompted us to perform a metabolomics analysis. Consistent with the decrease in CPT1, we found a significant decrease in C4/Ci4, C5-OH/C3-DC, C12:1, C14:1, C16:1, and C20:3 acyl carnitines in hearts from CypD(-/-) mice. In summary, CypD(-/-) hearts exhibit changes in many metabolic pathways and caution should be used when interpreting results from these mice as due solely to inhibition of the MPTP.

  1. Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers : Findings from a prospective cohort study

    NARCIS (Netherlands)

    Stepien, Magdalena; Duarte-Salles, Talita; Fedirko, Veronika; Floegel, Anne; Barupal, Dinesh Kumar; Rinaldi, Sabina; Achaintre, David; Assi, Nada; Tjønneland, Anne; Overvad, Kim; Bastide, Nadia; Boutron-Ruault, Marie Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Saieva, Calogero; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H. B.; Peeters, Petra H.; Weiderpass, Elisabete; Quirós, J. Ramón; Agudo, Antonio; Sánchez, María José; Dorronsoro, Miren; Gavrila, Diana; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Sund, Malin; Wareham, Nick; Khaw, Kay Tee; Travis, Ruth C.; Schmidt, Julie A.; Gunter, Marc; Cross, Amanda; Vineis, Paolo; Romieu, Isabelle; Scalbert, Augustin; Jenab, Mazda

    2016-01-01

    Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), a

  2. In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos

    Directory of Open Access Journals (Sweden)

    Subrat K. Bhanja

    2015-04-01

    Full Text Available Due to their physicochemical and biological properties, silver nanoparticles (NanoAg have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10 expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2 expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4 expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken.

  3. Anti-diabetic efficacy and impact on amino acid metabolism of GRA1, a novel small-molecule glucagon receptor antagonist.

    Directory of Open Access Journals (Sweden)

    James Mu

    Full Text Available Hyperglucagonemia is implicated in the pathophysiology of hyperglycemia. Antagonism of the glucagon receptor (GCGR thus represents a potential approach to diabetes treatment. Herein we report the characterization of GRA1, a novel small-molecule GCGR antagonist that blocks glucagon binding to the human GCGR (hGCGR and antagonizes glucagon-induced intracellular accumulation of cAMP with nanomolar potency. GRA1 inhibited glycogenolysis dose-dependently in primary human hepatocytes and in perfused liver from hGCGR mice, a transgenic line of mouse that expresses the hGCGR instead of the murine GCGR. When administered orally to hGCGR mice and rhesus monkeys, GRA1 blocked hyperglycemic responses to exogenous glucagon. In several murine models of diabetes, acute and chronic dosing with GRA1 significantly reduced blood glucose concentrations and moderately increased plasma glucagon and glucagon-like peptide-1. Combination of GRA1 with a dipeptidyl peptidase-4 inhibitor had an additive antihyperglycemic effect in diabetic mice. Hepatic gene-expression profiling in monkeys treated with GRA1 revealed down-regulation of numerous genes involved in amino acid catabolism, an effect that was paralleled by increased amino acid levels in the circulation. In summary, GRA1 is a potent glucagon receptor antagonist with strong antihyperglycemic efficacy in preclinical models and prominent effects on hepatic gene-expression related to amino acid metabolism.

  4. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 8

    International Nuclear Information System (INIS)

    Over 4 days 12 colostomized laying hens received, together with the ration, 36 g wheat with 14.37 atom-% 15N excess (15N'). The basic amino acids were nearly equally labelled. Three animals each were butchered after 12 h, 36 h, 60 h, and 108 h, resp., after the last 15N' application. Emission spectrometric determination of 15N' in liver and in amino acids was carried out. In addition, atom-% 15N' was determined in free amino acids and peptides. The labelling in the liver 12 h after the last 15N' application amounted to 1.75 atom-% 15N' and decreased after 108 h to 0.81 atom-% 15N'. The average TCA precipitable 15N' quota in the total 15N' amounted to 81.4% and was nearly identical at all four measuring points. The arginine 15N' amount in the liver was twice as high as that of lysine 15N'. In dependence on the period after the last 15N' application the decrease in the labelling of free arginine is considerable in comparison to free lysine. At the first measuring point (12 h) it was 1.69 atom-% 15N' and at the last one (108 h) 0.57 atom-% 15N'. Based on the results of 15N' labelling of peptides in the liver further, more detailed experiments for studies of peptide metabolism in the liver should be carried out. (author)

  5. Disposition and metabolism of the food mutagen 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, P.W.; Wallin, H.; Alexander, J.; Jaegerstad, M.

    1989-07-01

    The disposition and metabolism of a common food mutagen, 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), was studied in rats. Five rats of both sexes were given a single oral dose of /sup 14/C-labeled MeIQx (3-4 mg/kg body wt). The male rats excreted 36% of the radioactivity and 15% of the mutagenic activity of the dose given in the urine collected during the first 24 h. In the females the corresponding urine contained 41% of the radioactivity and 12% of the mutagenicity. During the next 48 h only 1-3% of the radioactive dose was excreted in urine. The remaining dose was excreted in the feces except of less than 1% that was retained by the tissues after 72 h. The liver and kidney retained more radioactivity than other organs. In a separate study the metabolites of bile, urine and feces of both sexes were investigated. After a single oral dose of 20 mg /sup 14/C-labeled MeIQx/kg body wt, three major non-mutagenic metabolites were identified. These were 2-amino-4(or 5)-(beta-D-glucuronopyranosyloxy)-3,8-dimethylimidazo(4,5-f) quinoxaline, 2-amino-3,8-dimethylimidazo(4,5-f)quinoxalin-4(or 5)-yl sulfate and N-(3,8-dimethylimidazo(4,5-f)quinoxalin-2-yl) sulfamate. Another two metabolites present in bile, urine and feces were 2-(beta-D-glucuronopyranosylamino)-3,8-dimethylimidazo(4,5-f ) quinoxaline and 2-amino-8-hydroxymethyl-3-methylimidazo(4,5-f)quinoxalin-4 (or 5)yl sulfate. All metabolites were essentially non-mutagenic. Most of the mutagenicity still present in bile, urine and feces could be explained by unchanged MeIQx. Unchanged MeIQx was the most abundant form excreted in urine.

  6. Selenate mitigates arsenite toxicity in rice (Oryza sativa L.) by reducing arsenic uptake and ameliorates amino acid content and thiol metabolism.

    Science.gov (United States)

    Kumar, Amit; Dixit, Garima; Singh, Amit Pal; Dwivedi, Sanjay; Srivastava, Sudhakar; Mishra, Kumkum; Tripathi, Rudra Deo

    2016-11-01

    Arsenic (As) is a toxic element with the potential to cause health effects in humans. Besides rice is a source of both amino acids (AAs) and mineral nutrients, it is undesired source of As for billions of people consuming rice as the staple food. Selenium (Se) is an essential metalloid, which can regulate As toxicity by strengthening antioxidant potential. The present study was designed to investigate As(III) stress mitigating effect of Se(VI) in rice. The level of As, thiolic ligands and AAs was analyzed in rice seedlings after exposure to As(III)/Se(VI) alone and As(III)+Se(VI) treatments. Selenate supplementation (As(III) 25μM+Se(VI) 25μM) decreased total As accumulation in both root and shoot (179 & 144%) as compared to As(III) alone treatment. The As(III)+Se(VI) treatment also induced the levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) as compared to As(III) alone treatment and also modulated the activity of enzymes of thiol metabolism. The content of amino acids (AAs) was significantly altered with Se(VI) supplementation. Importantly, essential amino acids (EAAs) were enhanced in As(III)+Se(VI) treatment as compared to As(III) alone treatment. In contrast, stress related non-essential amino acids (NEAAs) like GABA, Glu, Gly, Pro and Cys showed enhanced levels in As(III) alone treatment. In conclusion, rice supplemented with Se(VI) tolerated As toxicity with reduced As accumulation and increased the nutrition quality by increasing EAAs.

  7. Amino acids

    Science.gov (United States)

    ... amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan , and valine. Nonessential amino acids "Nonessential" means that our bodies produce an amino ...

  8. Amino Acid Crossword Puzzle

    Science.gov (United States)

    Sims, Paul A.

    2011-01-01

    Learning the 20 standard amino acids is an essential component of an introductory course in biochemistry. Later in the course, the students study metabolism and learn about various catabolic and anabolic pathways involving amino acids. Learning new material or concepts often is easier if one can connect the new material to what one already knows;…

  9. Using a genome-scale metabolic model of Enterococcus faecalis V583 to assess amino acid uptake and its impact on central metabolism

    NARCIS (Netherlands)

    N. Veith; M. Solheim; K.W.A. van Grinsven; B.G. Olivier; J. Levering; R. Grosseholz; J. Hugenholtz; H. Holo; I. Nes; B. Teusink; U. Kummer

    2015-01-01

    Increasing antibiotic resistance in pathogenic bacteria necessitates the development of new medication strategies. Interfering with the metabolic network of the pathogen can provide novel drug targets but simultaneously requires a deeper and more detailed organism-specific understanding of the metab

  10. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.;

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...

  11. Metabolism

    Science.gov (United States)

    ... also influenced by body composition — people with more muscle and less fat generally have higher BMRs. previous continue Things That Can Go Wrong With Metabolism Most of the time your metabolism works effectively ...

  12. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  13. Application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report of an IAEA consultants' meeting held in Vienna, Austria, 14-16 December 1992

    International Nuclear Information System (INIS)

    A Consultants' Meeting convened by the IAEA in December 1992, made recommendations on the organization of a Co-ordinated Research Programme (CRP) using stable isotopic techniques for international comparative studies of amino acid, protein, and energy metabolism in chronically undernourished people. The CRP will use recent developments in stable isotope tracer techniques (13C and 15N) to assess the impact of infection in undernourished people on the kinetics of protein breakdown, protein synthesis, amino acid metabolism, and on the synthetic rates of selected plasma proteins. Studies will be conducted in developing countries, particularly in young children. The programme goals are to (i) elaborate methods and model protocols which can be implemented in developing countries to investigate the impact on protein metabolism of infection superimposed on chronic undernutrition; (ii) test they hypothesis that dietary requirements for protein and amino acids are related to the place of nutrition and are altered substantially when infection is superimposed on chronic undernutrition. When feasible, the primary focus on protein/amino acid metabolism will be extended to assessments of protein/energy interactions when H218O becomes more readily available and/or at research sites with indirect calorimetry equipment. The data generated should be appropriate as a basis for reevaluating amino acid/protein requirements in these populations. Refs

  14. Skin metabolism of aminophenols: Human keratinocytes as a suitable in vitro model to qualitatively predict the dermal transformation of 4-amino-2-hydroxytoluene in vivo

    International Nuclear Information System (INIS)

    4-Amino-2-hydroxytolune (AHT) is an aromatic amine ingredient in oxidative hair colouring products. As skin contact occurs during hair dyeing, characterisation of dermal metabolism is important for the safety assessment of this chemical class. We have compared the metabolism of AHT in the human keratinocyte cell line HaCaT with that observed ex-vivo in human skin and in vivo (topical application versus oral (p.o.) and intravenous (i.v.) route). Three major metabolites of AHT were excreted, i.e. N-acetyl-AHT, AHT-sulfate and AHT-glucuronide. When 12.5 mg/kg AHT was applied topically, the relative amounts of each metabolite were altered such that N-acetyl-AHT product was the major metabolite (66% of the dose in comparison with 37% and 32% of the same applied dose after i.v. and p.o. administration, respectively). N-acetylated products were the only metabolites detected in HaCaT cells and ex-vivo whole human skin discs for AHT and p-aminophenol (PAP), an aromatic amine known to undergo N-acetylation in vivo. Since N-acetyltransferase 1 (NAT1) is the responsible enzyme, kinetics of AHT was further compared to the standard NAT1 substrate p-aminobenzoic acid (PABA) in the HaCaT model revealing similar values for Km and Vmax. In conclusion NAT1 dependent dermal N-acetylation of AHT represents a 'first-pass' metabolism effect in the skin prior to entering the systemic circulation. Since the HaCaT cell model represents a suitable in vitro assay for addressing the qualitative contribution of the skin to the metabolism of topically-applied aromatic amines it may contribute to a reduction in animal testing

  15. Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Yadav Sapkota

    Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

  16. Modification of the metabolism and cytotoxicity of bioreductive alkylating agents by dicoumarol in aerobic and hypoxic murine tumor cells.

    Science.gov (United States)

    Keyes, S R; Rockwell, S; Sartorelli, A C

    1989-06-15

    We have demonstrated previously that dicoumarol (DIC) increased the generation of reactive metabolites from mitomycin C (MC) in EMT6 cells under hypoxic conditions in vitro. This increased reaction rate was associated with an increased toxicity of MC to hypoxic EMT6 cells. In contrast, aerobic cells treated with DIC in vitro were protected from MC toxicity. We now demonstrate that DIC sensitizes EMT6 cells to two MC analogues, porfiromycin (POR) and the 7-N-dimethylaminomethylene analogue of mitomycin C (BMY-25282), in hypoxia and protects cells from these agents in air, despite the fact that POR is preferentially toxic to hypoxic cells and BMY-25282 is preferentially toxic to aerobic cells. In contrast, DIC increases menadione cytotoxicity in both air and hypoxia and has no effect on the cytotoxicity of Adriamycin. We have also shown previously that the preferential toxicity of POR to hypoxic cells is associated with an increased rate of drug uptake. In the present study, DIC had no measurable effect on the uptake of [3H]POR but increased the extent of efflux of this agent. MC-induced DNA cross-links, which have been proposed as the lesions responsible for the lethality of MC, are decreased by DIC in air and increased by DIC in hypoxia, in concert with the observed modifications of MC cytotoxicity by DIC. However, in aerobic cells treated with DIC and MC, the decrease in DNA interstrand cross-links is not directly associated with a decrease in cytotoxicity. L1210 cells, which have no measurable quinone reductase activity, demonstrate increased toxicity when treated with DIC and MC in hypoxia, as observed with EMT6 cells. Unlike EMT6 cells, however, L1210 cells are not protected by DIC from MC toxicity in air. Taken together, these findings suggest that DIC is altering the intracellular metabolism of MC and that quinone reductase or another, unidentified, enzyme sensitive to DIC may be involved in activating MC to a toxic product in aerobic EMT6 cells. PMID:2470504

  17. The effect of dietary protein on the amino acid supply and threonine metabolism in the pregnant rat

    OpenAIRE

    Rees, William; Hay, Susan; Antipatis, Christos

    2006-01-01

    International audience To characterise the effects of dietary protein content on threonine metabolism during pregnancy, rats were fed diets containing 18% or 9% protein and then killed at different stages of gestation. Serum threonine concentrations fell significantly faster in the animals fed the diet containing 9% protein when compared to those fed the diet containing 18% protein. On day 4 of gestation the rate of threonine oxidation was higher in maternal liver homogenates prepared from...

  18. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    Science.gov (United States)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-01-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution. PMID:27767182

  19. Effects of postprandial starvation on mRNA expression of endocrine-, amino acid and peptide transporter-, and metabolic enzyme-related genes in zebrafish (Danio rerio).

    Science.gov (United States)

    Tian, Juan; He, Gen; Mai, Kangsen; Liu, Chengdong

    2015-06-01

    The goal of this study was to systematically evaluate the molecular activities of endocrine-, amino acid and peptide transporters-, and metabolic enzyme-related genes in 35-day-old mixed-sex zebrafish (Danio rerio) after feeding . Zebrafish with initial body weights ranging from 9 to 11 mg were fasted for 384 h in a controlled indoor environment. Fish were sampled at 0, 3, 6, 12, 24, 48, 96, 192, and 384 h after fed. Overall, the present study results show that the regulatory mechanism that insulin-like growth factor I negative feedback regulated growth hormone is conserved in zebrafish, as it is in mammals, but that regulation of growth hormone receptors is highly intricate. Leptin and cholecystokinin are time-dependent negative feedback signals, and neuropeptide Y may be an important positive neuropeptide for food intake in zebrafish. The amino acid/carnitine transporters B(0,+) (ATB(0,+)) and broad neutral (0) amino acid transporter 1(B(0)AT1) mRNA levels measured in our study suggest that protein may be utilized during 24-96 h of fasting in zebrafish. Glutamine synthetase mRNA levels were downregulated, and glutamate dehydrogenase, alanine aminotransferase, aspartate transaminase, and trypsin mRNA levels were upregulated after longtime fasting in this study. The mRNA expression levels of fatty acid synthetase decreased significantly (P < 0.05), whereas those of lipoprotein lipase rapidly increased after 96 h of fasting. Fasting activated the expression of glucose synthesis genes when fasting for short periods of time; when fasting is prolonged, the mRNA levels of glucose breakdown enzymes and pentose phosphate shunt genes decreased. PMID:25805459

  20. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    Directory of Open Access Journals (Sweden)

    Hong SU

    2013-03-01

    determined by Western blotting. Results  The expression levels of p300, Ac-H3 and Ac-H4 protein in HG group increased, being 2.15, 1.93 and 1.87 fold of those in group NG (P<0.05, accompanying with the up-regulation of PKCβ2 protein and ROS levels in HG group. The p300, Ac-H3, Ac-H4, PKCβ2 protein expression and ROS levels in M1, M2, M3 group were higher than those in NG group, and was 1.75, 1.49, 1.47, 1.98 and 1.48 fold higher in M3 group than in NG group. The protein expressions of p300, Ac-H3 and Ac-H4 in AGEs group were increased by 1.73, 1.08 and 1.05 folds, and in AGE-M group increased by 1.47, 0.95 and 1.03 folds of that in control group (P<0.05. The protein expression levels of p300, Ac-H3 and Ac-H4 in H2O2 group increased by 1.03, 0.85 and 0.79 folds of those in control group (P<0.05. However, no significantly difference in these indices was found between H2O2-M and control groups. The protein expression levels of p300, Ac-H3 and Ac-H4 in PO group increased more obviously by 1.25, 1.06 and 1.10 folds of those in M group (P<0.05. However, the elective PKCβ2 inhibitor CGP53353 could lower those indices significantly. Conclusion  Persistent activation of transcriptional coactivator p300 and apparent modification may be normalized in HMCs. p300 may be the convergent point of glucose-induced metabolic "memory" stimulations.

  1. Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species.

    Science.gov (United States)

    Lushchak, Oleh V; Piroddi, Marta; Galli, Francesco; Lushchak, Volodymyr I

    2014-01-01

    Aconitase, an enzyme possessing an iron-sulfur cluster that is sensitive to oxidation, is involved in the regulation of cellular metabolism. There are two isoenzymes of aconitase (Aco)--mitochondrial (mAco) and cytosolic (cAco) ones. The primary role of mAdco is believed to be to control cellular ATP production via regulation of intermediate flux in the Krebs cycle. The cytosolic Aco in its reduced form operates as an enzyme, whereas in the oxidized form it is involved in the control of iron homeostasis as iron regulatory protein 1 (IRP1). Reactive oxygen species (ROS) play a central role in regulation of Aco functions. Catalytic Aco activity is regulated by reversible oxidation of [4Fe-4S]²⁺ cluster and cysteine residues, so redox-dependent posttranslational modifications (PTMs) have gained increasing consideration as regards possible regulatory effects. These include modifications of cysteine residues by oxidation, nitrosylation and thiolation, as well as Tyr nitration and oxidation of Lys residues to carbonyls. Redox-independent PTMs such as phosphorylation and transamination also have been described. In the presence of a sustained ROS flux, redox-dependent PTMs may lead to enzyme damage and cell stress by impaired energy and iron metabolism. Aconitase has been identified as a protein that undergoes oxidative modification and inactivation in aging and certain oxidative stress-related disorders. Here we describe possible mechanisms of involvement of the two aconitase isoforms, cAco and mAco, in the control of cell metabolism and iron homeostasis, balancing the regulatory, and damaging effects of ROS.

  2. Impact of 3-Amino-1,2,4-Triazole (3-AT-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Ruiz-Ojeda

    Full Text Available Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT, the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5 were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2 and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes.

  3. Impact of 3-Amino-1,2,4-Triazole (3-AT)-Derived Increase in Hydrogen Peroxide Levels on Inflammation and Metabolism in Human Differentiated Adipocytes

    Science.gov (United States)

    Ruiz-Ojeda, Francisco Javier; Gomez-Llorente, Carolina; Aguilera, Concepción María; Gil, Angel; Rupérez, Azahara Iris

    2016-01-01

    Obesity is characterized by an excessive accumulation of fat in adipose tissue, which is associated with oxidative stress and chronic inflammation. Excessive H2O2 levels are degraded by catalase (CAT), the activity of which is decreased in obesity. We investigated the effects of inhibition of catalase activity on metabolism and inflammation by incubating human differentiated adipocytes with 10 mM 3-amino-1,2,4-triazole (3-AT) for 24 h. As expected, the treatment decreased CAT activity and increased intracellular H2O2 levels significantly. Glutathione peroxidase (GPX) activity was also reduced, and the gene expression levels of the antioxidant enzymes GPX4 and peroxiredoxins (1, 3 and 5) were inhibited. Interestingly, this occurred along with lower mRNA levels of the transcription factors nuclear factor (erythroid 2-like 2) and forkhead box O, which are involved in redox homeostasis. However, superoxide dismutase activity and expression were increased. Moreover, 3-AT led to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and increased tumor necrosis alpha and interleukin 6 protein and gene expression levels, while lowering peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein levels. These alterations were accompanied by an altered glucose and lipid metabolism. Indeed, adipocytes treated with 3-AT showed reduced basal glucose uptake, reduced glucose transporter type 4 gene and protein expression, reduced lipolysis, reduced AMP-activated protein kinase activation and reduced gene expression of lipases. Our results indicate that increased H2O2 levels caused by 3-AT treatment impair the antioxidant defense system, lower PPARγ expression and initiate inflammation, thus affecting glucose and lipid metabolism in human differentiated adipocytes. PMID:27023799

  4. Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study.

    Science.gov (United States)

    Stepien, Magdalena; Duarte-Salles, Talita; Fedirko, Veronika; Floegel, Anne; Barupal, Dinesh Kumar; Rinaldi, Sabina; Achaintre, David; Assi, Nada; Tjønneland, Anne; Overvad, Kim; Bastide, Nadia; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Saieva, Calogero; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Gavrila, Diana; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Sund, Malin; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Schmidt, Julie A; Gunter, Marc; Cross, Amanda; Vineis, Paolo; Romieu, Isabelle; Scalbert, Augustin; Jenab, Mazda

    2016-01-15

    Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development. PMID:26238458

  5. Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial.

    Science.gov (United States)

    Chirinos, Diana A; Goldberg, Ronald B; Llabre, Maria M; Gellman, Marc; Gutt, Miriam; McCalla, Judith; Mendez, Armando; Schneiderman, Neil

    2016-06-01

    Although weight is an important intervention target among patients with metabolic syndrome, few trials have recruited low-income minority populations. The Community Health and Risk-reduction for Metabolic Syndrome randomized controlled trial aimed to examine the effects of a lifestyle intervention on weight and metabolic syndrome components among low-income minority adults. We randomized 120 adults with metabolic syndrome to standard medical care (N = 60) or a lifestyle intervention (N = 60). Using an intent-to-treat approach, we found significant intervention effects on weight [B = -0.452; SE = 0.122; 95 % confidence intervals (CI) -0.653 to -0.251) and glucose levels at 6-months (B = -0.522, SE = 0.234, 95 % CI -0.907 to -0.138). These changes were maintained through the 12-month assessment. No significant effects were observed on insulin resistance or other metabolic syndrome components. Our intervention was successful in achieving modest but significant weight loss and reduction in fasting glucose among low-income minority subjects with metabolic syndrome.

  6. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood ...

  7. Ozone impact on vegetation: phenolic metabolism modification and oxidative alteration of Rubisco in Phaseolus vulgaris L; Impact de l'ozone sur le vegetal: modification du metabolisme phenolique et alteration de la Rubisco chez Phaseolus vulgaris L.

    Energy Technology Data Exchange (ETDEWEB)

    Kanoun, M.

    2002-04-15

    In order to characterize and quantify, in semi-natural situation, the incidence of atmospheric pollution on some physiological and metabolic functions in plants, the aim of our work was to identify sub-cellular impact markers, in bean (Phaseolus vulgaris L.), able to characterize a chronic and realistic ozone pollution climate. Two criteria were chosen: the foliar phenolic metabolism and the Rubisco, the key enzyme of photosynthesis. Using Open Top Chambers system, we demonstrated that, according to concentration, exposure kinetic and leaf type, ozone could induce amount variations of some constitutive soluble phenolic and the synthesis of new phenolic (iso-flavonoids). In some cases, these disturbances were observed jointly with foliar injuries and/or biomass reduction. Concurrently, this chronic and moderate ozone exposure could also induce carbonyl formation in amino acid residues constitutive of Rubisco small subunit (Rubisco-SSU) and a reduction in the amount of the native Rubisco. The amount of a constitutive kaempferol glucuronide and the ozone-induced oxidative alteration of Rubisco-SSU were selected and tested for the construction of dose-response relationships. Whatever the marker, the linear model was able to describe the relation. For the phenolic response, several exposure indexes were tested. According to their mode of calculation, these exposure forms emphasize more or less the contribution of high ozone concentrations. If, for Rubisco oxidation, the use of the exposure index AOT40 seems relevant, in the case of the phenolic marker, the choice of the right index is leaf type dependant. (author)

  8. Roles of Bacteria in First-Pass Intestinal Metabolism of Amino Acids%细菌在氨基酸首过肠道代谢中的作用

    Institute of Scientific and Technical Information of China (English)

    杨宇翔; 慕春龙; 朱伟云

    2015-01-01

    Intestinal bacteria play important roles in nutrient metabolism, which furtherly affect body metabo-lism. Small intestine is the main region for amnio acids metabolism, and is critical to the host protein nutrition and gut health. However, large amount of amino acids entered into small intestine was degraded during the first-pass intestinal metabolism by bacteria. Amino acid metabolism in the small intestine is compartmentalized, not only segmented, but also layered. Amino acid metabolites, such as polyamine and dipeptide, are important for host gut health. Moreover, urea degradation and subsequent amino acid synthesis by the bacteria might be nutritionally valuable for the host. This article mainly reviewed the roles and out-ways in the first-pass intestinal metabolism of amino acids, metabolic compartments of amino acids, and the impacts of the metabolites on host health of small intestinal bacteria.%肠道细菌在营养素代谢过程中起重要作用,进而影响机体整体代谢。小肠是氨基酸代谢的重要场所,对宿主蛋白质营养与肠道健康至关重要。然而,大量进入小肠的氨基酸在首过肠道代谢中被细菌转化代谢和利用。此外,小肠细菌对氨基酸的代谢呈现出区室化特征,这不仅表现在不同肠段上,还体现在层面上的差异。细菌对氨基酸的代谢产物包括二肽、多胺,它们能影响宿主肠道健康,细菌分解尿素再合成氨基酸的功能可能在一定程度上缓解宿主对氨基酸的需求。本文主要综述了小肠细菌在氨基酸首过肠道代谢中的作用与去路、对氨基酸代谢的区室化以及氨基酸代谢产物对宿主的影响。

  9. [Influence of exogenous gamma-aminobutyric acid (GABA) on GABA metabolism and amino acid contents in roots of melon seedling under hypoxia stress].

    Science.gov (United States)

    Wang, Chun-Yan; Li, Jing-Rui; Xia, Qing-Ping; Wu, Xiao-Lei; Gao, Hong-Bo

    2014-07-01

    This paper investigated the influence of gamma-aminobutyric acid (GABA) on GABA metabolism and amino acid content under hypoxia stress by accurately controlling the level of dissolved oxygen in hydroponics, using the roots of melon 'Xiyu 1' seedlings as the test material. The results showed that compared with the control, the growth of roots was inhibited seriously under hypoxia stress. Meanwhile, the hypoxia-treated roots had significantly higher activities of glutamate decarboxylase (GAD), glutamate dehydrogenase (GDH), glutamate synthase (GOGAT), glutamine synthetase (GS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the contents of GABA, pyruvic acid, alanine (Ala) and aspartic acid (Asp). But the contents of glutamic acid (Glu) and alpha-keto glutaric acid in roots under hypoxia stress was obviously lower than those of the control. Exogenous treatment with GABA alleviated the inhibition effect of hypoxia stress on root growth, which was accompanied by an increase in the contents of endogenous GABA, Glu, alpha-keto glutaric acid and Asp. Furthermore, under hypoxia stress, the activities of GAD, GDH, GOGAT, GS, ALT, AST as well as the contents of pyruvic acid and Ala significantly decreased in roots treated with GABA. However, adding GABA and viny-gamma-aminobutyric acid (VGB) reduced the alleviation effect of GABA on melon seedlings under hypoxia stress. The results suggested that absorption of GABA by roots could alleviate the injury of hypoxia stress to melon seedlings. This meant that GABA treatment allows the normal physiological metabolism under hypoxia by inhibiting the GAD activity through feedback and maintaining higher Glu content as well as the bal- ance of carbon and nitrogen.

  10. Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

    Directory of Open Access Journals (Sweden)

    Hongyu Li

    Full Text Available Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

  11. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    OpenAIRE

    Su, Hong; Bo ZHOU; Ya-qian DUAN; Du, Chao

    2013-01-01

    Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3) and Ac-H4 in human renal mesangial cell (HMCs) as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d), high glucose group (HG, 25mmol/L D-glucose×2d), memory groups (M1, M2, M3, 25mmol/L...

  12. Dynamic Regulation of N-Methyl-d-aspartate (NMDA) and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors by Posttranslational Modifications.

    Science.gov (United States)

    Lussier, Marc P; Sanz-Clemente, Antonio; Roche, Katherine W

    2015-11-27

    Many molecular mechanisms underlie the changes in synaptic glutamate receptor content that are required by neuronal networks to generate cellular correlates of learning and memory. During the last decade, posttranslational modifications have emerged as critical regulators of synaptic transmission and plasticity. Notably, phosphorylation, ubiquitination, and palmitoylation control the stability, trafficking, and synaptic expression of glutamate receptors in the central nervous system. In the current review, we will summarize some of the progress made by the neuroscience community regarding our understanding of phosphorylation, ubiquitination, and palmitoylation of the NMDA and AMPA subtypes of glutamate receptors. PMID:26453298

  13. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls.

    Science.gov (United States)

    Zhang, Rong; Zhang, Tong; Ali, Ali Muhsen; Al Washih, Mohammed; Pickard, Benjamin; Watson, David G

    2016-01-01

    Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB), diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA) model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA) produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024). The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087). There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB. PMID:27076878

  14. Potential protein post-translational modifications and find potential single amino acid substitutions in hepatitis B large envelope protein Posibles modificaciones postranslacionales y sustituciones de un solo aminoácido en la proteína grande de la superficie del virus de la hepatitis B

    Directory of Open Access Journals (Sweden)

    V. Wiwanitkit

    2008-03-01

    Full Text Available Post-translational modifications of proteins control many biological processes. This is also important process in virus including hepatitis B. However, there is no in-depth study on the whole hepatitis B virus large envelope protein. In this work, potential protein post-translational modifications in hepatitis B virus large envelope protein were determined by a standard bioinformatics technique. Furthermore, potential single amino acid substitutions in hepatitis B large envelope protein were also determined. It can be seen that there are possible 3 potential protein were post-translational modifications with 1 possible single substitution. This data can be useful for further study on hepatitis B virus mutant as well as planning for new vaccine production.Las modificaciones postranslacionales que sufren las proteínas controlan muchos procesos biológicos. Esto es también válido en el caso de los virus, incluyendo el de la hepatitis B. Sin embargo, no se han realizado estudios en profundidad de la totalidad de la proteína grande de superficie del virus de la hepatitis B. En el presente estudio, se han determinado las modificaciones postranslacionales que son posibles en esta proteína de la cubierta viral empleando para ello una técnica bioinformática estándar. Además, también se determinaron las sustituciones de un solo aminoácido que son posibles en la proteína grande de la superficie del virus de la hepatitis B. De este análisis podemos deducir que existen 3 posibles modificaciones translacionales en esta proteína y una potencial sustitución simple. Estos datos pueden ser útiles tanto para posteriores estudios sobre el virus mutante de la hepatitis B, como para la producción de una nueva vacuna contra este virus.

  15. Metabolic model of Synechococcus sp. PCC 7002: Prediction of flux distribution and network modification for enhanced biofuel production.

    Science.gov (United States)

    Hendry, John I; Prasannan, Charulata B; Joshi, Aditi; Dasgupta, Santanu; Wangikar, Pramod P

    2016-08-01

    Flux Balance Analysis was performed with the Genome Scale Metabolic Model of a fast growing cyanobacterium Synechococcus sp. PCC 7002 to gain insights that would help in engineering the organism as a production host. Gene essentiality and synthetic lethality analysis revealed a reduced metabolic robustness under genetic perturbation compared to the heterotrophic bacteria Escherichia coli. Under glycerol heterotrophy the reducing equivalents were generated from tricarboxylic acid cycle rather than the oxidative pentose phosphate pathway. During mixotrophic growth in glycerol the photosynthetic electron transport chain was predominantly used for ATP synthesis with a photosystem I/photosystem II flux ratio higher than that observed under autotrophy. An exhaustive analysis of all possible double reaction knock outs was performed to reroute fixed carbon towards ethanol and butanol production. It was predicted that only ∼10% of fixed carbon could be diverted for ethanol and butanol production.

  16. Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells

    OpenAIRE

    Lei Zhang; Xiao-Jie Miao; Xin Wang; Hai-Hui Pan; Pu Li; Hong Ren; Yong-Rui Jia; Chuang Lu; Hong-Bing Wang; Lan Yuan; Guo-Liang Zhang

    2016-01-01

    Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine...

  17. Changes in Free Amino Acid Concentration in Rye Grain in Response to Nitrogen and Sulfur Availability, and Expression Analysis of Genes Involved in Asparagine Metabolism.

    Science.gov (United States)

    Postles, Jennifer; Curtis, Tanya Y; Powers, Stephen J; Elmore, J S; Mottram, Donald S; Halford, Nigel G

    2016-01-01

    Free asparagine plays a central role in nitrogen storage and transport in many plant species due to its relatively high ratio of nitrogen to carbon. However, it is also a precursor for acrylamide, a Class 2a carcinogen that forms during high-temperature processing and cooking. The concentration of free asparagine was shown to increase by approximately 70% in rye grain in response to severe sulfur deficiency (F-test, p = 0.004), while the concentration of both free asparagine and free glutamine increased (by almost threefold and approximately 62%, respectively) in response to nitrogen application (F-test, p supply on other free amino acids: The concentration of free proline, for example, showed a significant (F-test, p = 0.019) effect of nitrogen interacting with sulfur, with the highest concentration occurring when the plants were deprived of both nitrogen and sulfur. Polymerase chain reaction products for several genes involved in asparagine metabolism and its regulation were amplified from rye grain cDNA. These genes were asparagine synthetase-1 (ScASN1), glutamine synthetase-1 (ScGS1), potassium-dependent asparaginase (ScASP), aspartate kinase (ScASK), and general control non-derepressible-2 (ScGCN2). The expression of these genes and of a previously described sucrose non-fermenting-1-related protein kinase-1 gene (ScSnRK1) was analyzed in flag leaf and developing grain in response to nitrogen and sulfur supply, revealing a significant (F-test, p supply on ScGS1 expression in the grain at 21 days post-anthesis. There was also evidence of an effect of sulfur deficiency on ScASN1 gene expression. However, although this effect was large (almost 10-fold) it was only marginally statistically significant (F-test, 0.05 < p < 0.10). The study reinforced the conclusion that nutrient availability can have a profound impact on the concentrations of different free amino acids, something that is often overlooked by plant physiologists but which has important implications for

  18. Self-management for obesity and cardio-metabolic fitness: Description and evaluation of the lifestyle modification program of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Coates Alison M

    2008-10-01

    Full Text Available Abstract Background Sustainable lifestyle modification strategies are needed to address obesity and cardiovascular risk factors. Intensive, individualised programs have been successful, but are limited by time and resources. We have formulated a group-based lifestyle education program based upon national diet and physical activity (PA recommendations to manage obesity and cardio-metabolic risk factors. This article describes the content and delivery of this program, with information on compliance and acceptability. Methods Overweight/obese adults (n = 153 with metabolic syndrome were recruited from the community and randomly allocated to intervention (INT or control (CON. Written copies of Australian national dietary and PA guidelines were provided to all participants. INT took part in a 16-week lifestyle program which provided a curriculum and practical strategies on 1 dietary and PA information based on national guidelines, 2 behavioural self-management tools, 3 food-label reading, supermarkets tour and cooking, 4 exercise sessions, and 5 peer-group support. Compliance was assessed using attendance records and weekly food/PA logs. Participants' motivations, perceived benefits and goals were assessed through facilitated discussion. Program acceptability feedback was collected through structured focus groups. Results Although completion of weekly food/PA records was poor, attendance at information/education sessions (77% overall and exercise participation (66% overall was high, and compared with CON, multiple markers of body composition and cardio-metabolic health improved in INT. Participants reported that the most useful program components included food-label reading, cooking sessions, and learning new and different physical exercises, including home-based options. Participants also reported finding self-management techniques helpful, namely problem solving and short-term goal setting. The use of a group setting and supportive 'peer' leaders

  19. Effects of supplementation with branched-chain amino acids to low-protein diets on expression of genes related to lipid metabolism in skeletal muscle of growing pigs.

    Science.gov (United States)

    Duan, Yehui; Duan, Yangmiao; Li, Fengna; Li, Yinghui; Guo, Qiuping; Ji, Yujiao; Tan, Bie; Li, Tiejun; Yin, Yulong

    2016-09-01

    Branched-chain amino acids (BCAA), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in energy homeostasis and lipid metabolism in addition to their other functions, such as in protein metabolism. This study investigated the effects of different dietary BCAA ratios on the intramuscular fat (IMF) content and fatty acid composition in different location of skeletal muscles, including the longissimus dorsi (LD), biceps femoris (BF), and psoas major (PM) muscles of growing pigs, and also examined the mRNA expression levels of genes involved in lipid metabolism in these muscle tissues. The experiment was performed on 40 growing pigs (Large White × Landrace) with a similar initial weight (9.85 ± 0.35 kg). The pigs were randomly assigned to one of five diets: diet A was a positive control and contained 20 % crude protein (CP) with a Leu:Ile:Val ratio of 1:0.51:0.63 according to the recommendation of the National Research Council (NRC); for diets B to E, the CP level was reduced to 17 %, and the Leu:Ile:Val ratios were 1:1:1, 1:0.75:0.75, 1:0.51:0.63, and 1:0.25:0.25, respectively. No significant difference was observed in the average feed intake and feed efficiency of the pigs fed the low protein diet (17 % CP) with BCAA treatments relative to the positive control. However, there was a tendency for increased feed efficiency of the 1:0.75:0.75 group compared with the 1:1:1 group (P = 0.09). The BCAA ratio of 1:0.75:0.75 (17 % CP) increased the IMF content of BF muscle (P protein level had different effects on the fatty acid composition of the LD, BF, and PM muscles. The BCAA ratio of 1:0.51:0.63-1:0.75:0.75 (17 % CP) significantly lowered the ratio of n-6 to n-3 polyunsaturated fatty acid in these muscles compared with the positive control group (20 % CP). This effect was associated with an increase in mRNA expression levels of acetyl-CoA carboxylase, lipoprotein lipase, fatty acid transport protein, and fatty acid binding

  20. 氨基酸感应与糖脂代谢调控的研究进展%Research progress on amino acid sensing and its role in the regulation of glucose and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    吕子全; 郭非凡

    2013-01-01

    氨基酸是机体必需的小分子代谢物,其作为信号分子广泛参与了对机体糖脂代谢稳态的维持和调控.研究表明,在糖脂能量代谢的调节过程中,支链氨基酸(尤其是亮氨酸)发挥了重要作用.机体与糖脂代谢相关的多个外周脏器(如肝脏、胰腺、白脂、褐脂、胃肠道等)和代谢调控中枢下丘脑均可以感应外界氨基酸水平的变化,并调节糖脂能量代谢.此外,氨基酸调节糖脂代谢的关键信号通路也已被广泛证实,如mTOR/S6K信号通路、GCN2/ATF4信号通路等.鉴于2型糖尿病等营养相关慢性代谢病的发病率不断攀升,对氨基酸的营养感应和糖脂代谢调控功能进行进一步探索将为代谢性疾病的防控提供重要的指导意义.%Amino acid is a type of micro-molecular metabolite essential for the maintenance of life. As a signal transducing molecule, amino acid extensively participates in the maintenance and regulation of glucose and lipid metabolism homeostasis. Previous research has confirmed the crucial role of amino acid, especially branched chain amino acid (BCAA; e.g., leucine) in the regulation of glucose/lipid and energy homeostasis. The metabolic control center hypothalamus, as well as multiple periphery organs correlated with glucose and lipid metabolism (such as liver, pancreas, white adipose tissue, brown adipose tissue, gastrointestinal tract) can sense the level of amino acid in external environment, and regulate glucose/lipid and energy metabolism. What is more, key signal transduction pathways affected by amino acid in the modulation of glucose and lipid metabolism have been well established, such as mTOR/S6K, GCN2/ATF4 pathway. In the view of constant increase of chronic metabolic diseases such as type 2 diabetes, further exploring on amino acid nutrient sensing and its metabolic control on glucose and lipid metabolism will provide significant guidance for the prevention and control of metabolic diseases.

  1. Rationale and design of a proof-of-concept trial investigating the effect of uninterrupted perioperative (par)enteral nutrition on amino acid profile, cardiomyocytes structure, and cardiac perfusion and metabolism of patients undergoing coronary artery bypass grafting

    OpenAIRE

    Cocchieri Riccardo; van Venrooij Lenny MW; Niessen Hans WM; Kok Wouter EM; Verberne Hein J; Davids Mariska; Visser Marlieke; Wisselink Willem; de Mol Bas AJM; van Leeuwen Paul AM

    2011-01-01

    Abstract Background Malnutrition is very common in patients undergoing cardiac surgery. Malnutrition can change myocardial substrate utilization which can induce adverse effects on myocardial metabolism and function. We aim to investigate the hypothesis that there is a disturbed amino acids profile in the cardiac surgical patient which can be normalized by (par)enteral nutrition before, during and after surgery, subsequently improving cardiomyocyte structure, cardiac perfusion and glucose met...

  2. Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

    OpenAIRE

    Qiu-Yi Wang; Yong Song; Wei Huang; Li Xiao; Qiu-Shi Wang; Gui-Mei Feng

    2016-01-01

    Background: While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Methods: Ninety-nine women with PCOS...

  3. Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells.

    Science.gov (United States)

    Zhang, Lei; Miao, Xiao-Jie; Wang, Xin; Pan, Hai-Hui; Li, Pu; Ren, Hong; Jia, Yong-Rui; Lu, Chuang; Wang, Hong-Bing; Yuan, Lan; Zhang, Guo-Liang

    2016-01-01

    Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic. PMID:27311637

  4. Is the habitation of acidic-water sanctuaries by galaxiid fish facilitated by natural organic matter modification of sodium metabolism?

    Science.gov (United States)

    Glover, Chris N; Donovan, Katherine A; Hill, Jonathan V

    2012-01-01

    Acidic waters of New Zealand's West Coast are hypothesized to be a refuge for native galaxiid fish, allowing them to escape predation from acid-sensitive invasive salmonid species. To determine the mechanisms by which galaxiids tolerate low pH, we investigated sodium metabolism in inanga Galaxias maculatus in response to water pH, short-term acclimation to acidic waters, the presence and source of natural organic matter (NOM), and fish life history. Contrary to expectation, inanga were physiologically sensitive to acid exposure, displaying inhibited sodium influx and exacerbated sodium efflux. Short-term (144 h) acclimation to acid did not modify this effect, and NOM did not exert a protective effect on sodium metabolism at low pH. Inanga sourced from naturally acidic West Coast waters did, however, display a sodium influx capacity (J(max)) that was significantly elevated when compared with that of fish collected from neutral waters. All inanga, independent of source, exhibited exceptionally high sodium uptake affinities (18-40 μM) relative to previously studied freshwater teleosts. Although inanga displayed relatively poor physiological tolerance to acidic waters, their high sodium influx affinity coupled with their occupation of near-coastal waters with elevated sodium levels may permit habitation of low-pH freshwaters. PMID:22902374

  5. Host plant-dependent metabolism of 4-hydroxybenzylglucosinolate in Pieris rapae: substrate specificity and effects of genetic modification and plant nitrile hydratase.

    Science.gov (United States)

    Agerbirk, Niels; Olsen, Carl Erik; Topbjerg, Henrik Bak; Sørensen, Jens Christian

    2007-11-01

    After ingestion of transgenic Arabidopsis thaliana CYP79A1 containing sinalbin (4-hydroxybenzylglucosinolate) due to genetic modification, only one major sinalbin-derived sulphate ester (the sulphate ester of 4-hydroxyphenylacetonitrile) was excreted by Pieris rapae caterpillars (corresponding to 69mol% of ingested sinalbin). An additional sulphate ester (the sulphate ester of 4-hydroxyphenylacetamide) was excreted when the caterpillars were reared on two plant species (Sinapis alba and Sinapis arvensis) that contained sinalbin naturally. Artificial addition of sinalbin to S. arvensis leaves resulted in increased levels of the sulphated amide, and an enzymatic activity (nitrile hydratase) explaining the formation of the sulphated amide from sinalbin was detected in both Sinapis species, but not in A. thaliana. In agreement with the suggested minor metabolic pathway, the caterpillars were able to sulphate 4-hydroxyphenylacetamide offered as part of an artificial diet. In fact, phenol and seven para-substituted phenol derivatives with substituents of moderate size were sulphated and excreted, but all tested phenols devoid of a nitrile functional group were less efficiently sulphated than the primary sinalbin detoxification product, 4-hydroxyphenylacetonitrile. This suggests that the specificity of the sulphation step involved in sinalbin metabolism may be adapted to nitriles formed as metabolites of phenolic glucosinolates. On the contrary, there was no specificity for products (4-hydroxybenzylascorbigen and 4-hydroxybenzylalcohol) derived from the semistable isothiocyanate produced from sinalbin in the absence of nitrile specifier protein. PMID:17916498

  6. Maternal Betaine Supplementation throughout Gestation and Lactation Modifies Hepatic Cholesterol Metabolic Genes in Weaning Piglets via AMPK/LXR-Mediated Pathway and Histone Modification

    Science.gov (United States)

    Cai, Demin; Yuan, Mengjie; Liu, Haoyu; Pan, Shifeng; Ma, Wenqiang; Hong, Jian; Zhao, Ruqian

    2016-01-01

    Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring. PMID:27763549

  7. Metabolic profile modifications in milk after enrofloxacin administration studied by liquid chromatography coupled with high resolution mass spectrometry.

    Science.gov (United States)

    Junza, A; Saurina, J; Barrón, D; Minguillón, C

    2016-08-19

    High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. PMID:27425761

  8. Engineering Escherichia coli to overproduce aromatic amino acids and derived compounds.

    Science.gov (United States)

    Rodriguez, Alberto; Martínez, Juan A; Flores, Noemí; Escalante, Adelfo; Gosset, Guillermo; Bolivar, Francisco

    2014-09-09

    The production of aromatic amino acids using fermentation processes with recombinant microorganisms can be an advantageous approach to reach their global demands. In addition, a large array of compounds with alimentary and pharmaceutical applications can potentially be synthesized from intermediates of this metabolic pathway. However, contrary to other amino acids and primary metabolites, the artificial channelling of building blocks from central metabolism towards the aromatic amino acid pathway is complicated to achieve in an efficient manner. The length and complex regulation of this pathway have progressively called for the employment of more integral approaches, promoting the merge of complementary tools and techniques in order to surpass metabolic and regulatory bottlenecks. As a result, relevant insights on the subject have been obtained during the last years, especially with genetically modified strains of Escherichia coli. By combining metabolic engineering strategies with developments in synthetic biology, systems biology and bioprocess engineering, notable advances were achieved regarding the generation, characterization and optimization of E. coli strains for the overproduction of aromatic amino acids, some of their precursors and related compounds. In this paper we review and compare recent successful reports dealing with the modification of metabolic traits to attain these objectives.

  9. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 10

    International Nuclear Information System (INIS)

    Over a period of 4 days 12 colostomized laying hens daily received 36 g coarse wheat meal containing 14.37 atom-% 15N excess (15N') together with a conventional ration. After the homogenisation of each oviduct N and 15N' were determined. After the precipitation with TCA the 15N' of the amino acids was analysed in both the precipitate and the supernatant. In addition, the free amino acids and the peptides were determined in the TCA soluble fraction. The atom-% 15N' in the total N and in the non-basic amino acid N showed a parallel decrease; it diminshed from 1.75 atom-% 15N' to 0.64. Of the three basic amino acids, lysine shows the lowest labelling at all four measuring points. The quotas of non-basic amino acid 14N and 15N' in the total 14N and 15N' of the oviduct are the same and amount to 53%. In contrast to this, the quota of the 14N of the basic amino acids in the total 14N of the oviduct only amounts to 21.6% and that of 15N' only to 15.4%. The average atom-% 15N' of the free amino acids 12 h after the last 15N application is 1.54 and is considerably above that of the peptides with 1.15 atom-% 15N'. 36 h after the last 15N application the ascertained value of 1.25 is identical in both fractions. The labelling of the free amino acids decreases more quickly than that of the peptides the more time has passed after the last 15N application. (author)

  10. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 7

    International Nuclear Information System (INIS)

    In a 15N labelling experiment 12 colostomized laying hens received 15N-labelled wheat with 14.37 atom-% 15N excess (15N') over 4 days. 3 hens each were butchered after 12 h, 36 h, 60 h and 108 h after the last 15N' application. The gastrointestinal tract was divided into 3 parts (esophagus with crop and gizzard as well as glandular stomach, small intestine, large intestine). These parts and the pancreas were hydrolyzed with 6 N HCl and the individual basic as well as the sum of acid and neutral amino acids were determined in the hydrolyzed fractions. In addition, the amino acids and peptides were determined in the TCA soluble N fraction. The atom-% 15N' was determined in the individual amino acid and peptide fractions. The labelling of the basic amino acids in the individual tract segments was lower than in the acid and neutral amino acids. In comparison to the peptides, a higher atom-% 15N' could be determined in the free amino acids. (author)

  11. Metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in human hepatocytes: 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid is a major detoxification pathway catalyzed by cytochrome P450 1A2.

    Science.gov (United States)

    Langouët, S; Welti, D H; Kerriguy, N; Fay, L B; Huynh-Ba, T; Markovic, J; Guengerich, F P; Guillouzo, A; Turesky, R J

    2001-02-01

    Metabolic pathways of the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) remain incompletely characterized in humans. In this study, the metabolism of MeIQx was investigated in primary human hepatocytes. Six metabolites were characterized by UV and mass spectroscopy. Novel metabolites were additionally characterized by 1H NMR spectroscopy. The carcinogenic metabolite, 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline, which is formed by cytochrome P450 1A2 (P450 1A2), was found to be transformed into the N(2)-glucuronide conjugate, N(2)-(beta-1-glucosiduronyl)-2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline. The phase II conjugates N(2)-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)sulfamic acid and N(2)-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, as well as the 7-oxo derivatives of MeIQx and N-desmethyl-MeIQx, 2-amino-3,8-dimethyl-6-hydro-7H-imidazo[4,5-f]quinoxalin-7-one (7-oxo-MeIQx), and 2-amino-6-hydro-8-methyl-7H-imidazo[4,5-f]quinoxalin-7-one (N-desmethyl-7-oxo-MeIQx), thought to be formed exclusively by the intestinal flora, were also identified. A novel metabolite was characterized as 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH), and it was the predominant metabolite formed in hepatocytes exposed to MeIQx at levels approaching human exposure. IQx-8-COOH formation is catalyzed by P450 1A2. This metabolite is a detoxication product and does not induce umuC gene expression in Salmonella typhimurium strain NM2009. IQx-8-COOH is also the principal oxidation product of MeIQx excreted in human urine [Turesky, R., et al. (1998) Chem. Res. Toxicol. 11, 217-225]. Thus, P450 1A2 is involved in both the metabolic activation and detoxication of this procarcinogen in humans. Analogous metabolism experiments were conducted with hepatocytes of untreated rats and rats pretreated with the P450 inducer 3-methylcholanthrene. Unlike human hepatocytes, the rat cell preparations did not produce IQx-8

  12. D-Serine metabolism in C6 glioma cells: Involvement of alanine-serine-cysteine transporter (ASCT2) and serine racemase (SRR) but not D-amino acid oxidase (DAO)

    OpenAIRE

    Sikka, Pilleriin; Walker, Rosie; Cockayne, Rebecca; Wood, Matthew JA; Harrison, Paul J; Burnet, Philip WJ

    2010-01-01

    D-serine is an endogenous N-methyl-D-aspartate (NMDA) receptor coagonist. It is synthesized from L-serine by serine racemase (SRR), but many aspects of its metabolism remain unclear, especially in the forebrain, which lacks active D-amino acid oxidase (DAO), the major D-serine degradative enzyme. Candidate mechanisms include SRR operating in α,β-eliminase mode (converting D-serine to pyruvate) and regulation by serine transport, in which the alanine-serine-cysteine transporter ASCT2 is implic...

  13. Analysis of 26 amino acids in human plasma by HPLC using AQC as derivatizing agent and its application in metabolic laboratory.

    Science.gov (United States)

    Sharma, Gaurav; Attri, Savita Verma; Behra, Bijaylaxmi; Bhisikar, Swapnil; Kumar, Praveen; Tageja, Minni; Sharda, Sheetal; Singhi, Pratibha; Singhi, Sunit

    2014-05-01

    The present study reports the simultaneous analysis of 26 physiological amino acids in plasma along with total cysteine and homocysteine by high-performance liquid chromatography (HPLC) employing 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) as precolumn derivatizing reagent. Separations were carried out using Lichrospher 100 RP-18e (5 μm) 250 × 4.0 mm column connected to 100 CN 4.0 × 4.0 mm guard column on a quaternary HPLC system and run time was 53 min. Linearity of the peak areas for different concentrations ranging from 2.5 to 100 pmol/μL of individual amino acids was determined. A good linearity (R (2) > 0.998) was achieved in the standard mixture for each amino acid. Recovery of amino acids incorporated at the time of derivatization ranged from 95 to 106 %. Using this method we have established the normative data of amino acids in plasma, the profile being comparable to the range reported in literature and identified cases of classical homocystinuria, cobalamin defect/deficiency, non-ketotic hyperglycinemia, hyperprolinemia, ketotic hyperglycinemia, urea cycle defect and maple syrup urine disease.

  14. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 9

    International Nuclear Information System (INIS)

    Over 4 days 12 colostomized laying hens received 36 g coarse wheat meal with a 15N excess (15N') of 14.37 atom-% together with a conventional diet. The labelling of lysine amounted to 13.58 atom-% 15N', that of histidine to 14.38 and of arginine to 13.63 atom-% 15N'. Three animals each were butchered 12 h, 36 h, 60 h and 108 h after the last 15N application. In the two charges of follicles (above and below 25 g) N and 15N' were determined in the individual basic amino acids as well as their sum in the non-basic ones. The atom-% 15N' was determined in the TCA soluble fraction of the free amino acid and peptide fractions. The average atom-% 15N' of the big follicles is 12 and 36 h after the last 15N application lower, and higher at the last two measuring points than that of the medium and small follicles. The atom-% of the total nitrogen and of the non-basic amino acids was significantly higher in both the bigger and the smaller follicles than in the basic amino acids. 70% of the heavy nitrogen in the total 15N' of the big follicles could be detected in amino acids; its quota in the small follicles was 67%. (author)

  15. β-氨基丁酸诱导水稻稻瘟病抗性对活性氧代谢的影响%Effects of β-Amino Butyric Acid Induced Rice Blast Resistance on Reactive Oxygen Metabolism

    Institute of Scientific and Technical Information of China (English)

    李莉; 郭晓丽; 刘晓梅; 温嘉伟; 张秀容; 孙辉; 赵宇; 任金平

    2009-01-01

    [Objective] This study was to understand the effects of β-Amino butyric acid(abbreviated as BABA) induced rice blast resistance on reactive oxygen metabolism. [Method] Using the cultivar Chaochan 2 that is highly susceptible to disease as experimental material, the changes of catalase(CAT), and superoxide dismutase(SOD) and MDA activities in rice treated by BABA were investigated. [Result] In rice plants treated by BABA, the activities of CAT and SOD increased, meanwhile the MDA content also rose to some extent, resulting in the disease resistance to rice blast. [Conclusion] By influencing reactive oxygen metabolism, BABA endows rice plants with resistance to rice blast. BABA is safe to environment and has highly resistance-inducing capacity, it could be generalized in production.

  16. 人早期胚胎解冻后氨基酸代谢变化的研究%Research on amino acid metabolism of human early embryo after frozen-thawed

    Institute of Scientific and Technical Information of China (English)

    唐杰; 方丛; 李婷婷; 张敏芳; 梁晓燕

    2011-01-01

    Objective: To study the amino acid metabolism of human early frozen-thawed embryo.Methods: Eighteen spare human embryos obtained from 13 patients undergoing in vitro ferbilization (IVF) were researched.Spare human embryos on day 3 of development were cultured individually in 20 μl drops of pre-equilibrated blastocyst culture medium for 2 hours before vitrification.Embryo-free drops were incubated in the same dish as the controls.The remaining 15 μl mediums from the drops were collected before freezing, 1/2,1,2,4,6 and 24 hours after thawing, and were analyzed for 20 free amino acids level by high performance liquid chromatography ( HPLC).Results: The levels of glutamine, histidine, tryptophan and lysine in blank controls were different among different time points.However, they were not increased or decreased gradually.The concentrations of other 16 amino acids remained same at different time points.One hour after thawing, concentrations of 20 free amino acids were all increased comparing with the blank control at same time point; the amino acid appearance and turnover was significant higher than that pre-freezing ( P < 0.05).The amino acid appearance had no significant difference betweem 2, 6 or 24 hours after thawing and pre-freezing ( P > 0.05).The amino acid depletion pre-freezing was significant lower than that 1/2, 4, 6 and 24 hours after thawing (P <0.05).The amino acid appearance 1/2 and 4 hours after thawing was significant lower than that pre-freezing ( P < 0.05).There was no significant difference in amino acid turnover between 1/2,4 hours after thawing and pre-freezing (P > 0.05).The amino acid turnover 24 hours after thawing was significant higher than that pre-freezing (P < 0.05).The amino acid turnover 1/2,4 and 6 hours after thawing were significant lower than that 1 hour after thawing (P <0.05).Conclusion: Human early embryo begins amino acid metabolism and recovers from metabolism stasis 1/2 hour after embryo thawing , and the amino

  17. Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord;

    2011-01-01

    Branched-chain amino acids (BCAA) are used in attempts to reduce blood ammonia in patients with cirrhosis and intermittent hepatic encephalopathy based on the hypothesis that BCAA stimulate muscle ammonia detoxification. We studied the effects of an oral dose of BCAA on the skeletal muscle metabo...

  18. Simulating the covalent modification of Fe(Ⅲ)-salophen with amino acid histidine or dipeptide Cys-His%氨基酸His或二肽Cys-His共价修饰Fe(Ⅲ)-salophen的计算机模拟

    Institute of Scientific and Technical Information of China (English)

    林英武

    2007-01-01

    Comparing with the structure of heme group that covalently linked to the polypeptide chain in natural heme proteins, we simulated the covalent modification of artificial Fe(Ⅲ)-salophen complex with amino acid histidine (His) or dipeptide cysteinyl-histidine (Cys-His), with the intention of providing useful information for design of metalloproteins containing nonnatural prosthetic group. By using molecular mechanics MM+ method, the molecular geometries were optimized, and then the single point calculation was carried out on the obtained structure with minimum energy by using semi-empirical ZINDO/1 method. Results illustrate that, with His serving as the fifth ligand of Fe(Ⅲ)-salophen, the molecule would be more stable when it was modified covalently, through forming an amide bond with His, by introducing a propionic group rather than a formic group. At the same time,the molecule would be more stable as modification occurred at position a rather than b of Fe(Ⅲ)-salophen, for both cases of His and Cys-His modification. In addition, of all these modified complexes, the most stable molecule was that being modified with dipeptide Cys-His at position a through a thioether bond that formed between the cysteine residue and an introduced vinyl group. This conformation consists with that found in natural c-type cytochromes. The current study presents the initial theoretical results, which could instruct the successful construction of functional Fe(Ⅲ)-salophen complex, and also direct its application in artificial metalloproteins design.%通过比较天然血红素蛋白中血红素与多肽链进行共价连接的结构,我们对组氨酸(His)或二肽半胱氨酰-组氨酸(Cys-His)共价修饰人工配合物Fe(Ⅲ)-salophen进行了计算机模拟,旨在为设计包含非天然辅基的金属蛋白分子提供有用的信息.修饰物采用分子力学MM+方法进行了分子构型优化,而且在最低能量构型的基础上,采用半经验量子化学ZINDO/1方

  19. Co-ordinated research programme on application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report on the second research co-ordination meeting

    International Nuclear Information System (INIS)

    The use of isotopes has revolutionized the field of human nutrition research, but has been of greatest benefit to industrialized countries. The International Atomic Energy Agency is sponsoring programmes using isotopic and related technologies in human nutrition research to address issues that are of priority to developing countries. Scientists participating in the Coordinated Research Programme (CRP) on ''Amino Acid and Protein Metabolism in Malnourished Populations of Developing Countries'' are conducting research on the interaction between infection and amino acid metabolism, particularly the potential diversion of substrates from anabolic pathways to fight infection in marginally nourished children during periods of infections. This topic is of great importance to the nutritional status of children in developing countries, who frequently or chronically have infections and who, as a consequence, may have alterations in nutrient requirements. The CRP has developed and implemented a standardized protocol for measuring leucine oxidation during infection in 8 different countries. The CRP is expected to contribute important new knowledge about interactions between protein utilization, the stresses of unhygienic environments, and infections in marginally nourished people. This information is expected to be applicable to efforts to increase efficient utilization of limited food resources in developing countries. Another highlight of the CRP is that it represents an international team of nutrition scientists who together are building nutritional biology research capabilities in developing countries. Refs, figs, tabs

  20. Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis

    DEFF Research Database (Denmark)

    Rodriguez Prado, Edith Angelica; Kildegaard, Kanchana Rueksomtawin; Li, Mingji;

    2015-01-01

    Aromatic amino acids are precursors of numerous plant secondary metabolites with diverse biological functions. Many of these secondary metabolites are already being used as active pharmaceutical or nutraceutical ingredients, and there are numerous exploratory studies of other compounds...... with promising applications. p-Coumaric acid is derived from aromatic amino acids and, besides being a valuable chemical building block, it serves as precursor for biosynthesis of many secondary metabolites, such as polyphenols, flavonoids, and some polyketides. Here we developed a p-coumaric acid...... was obtained, when overexpressing tyrosine ammonia-lyase TAL from Flavobacterium johnsoniaeu, DAHP synthase ARO4K229L, chorismate mutase ARO7G141S and E. coli shikimate kinase II (aroL) in Δpdc5Δaro10 strain background. To our knowledge this is the highest reported titer of an aromatic compound produced...

  1. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 11

    International Nuclear Information System (INIS)

    Over a period of 4 days 12 colostomized laying hens daily received 36 g 15N-labelled wheat with 15N excess (15N') of 14.37 atom-% together with a conventional feed mixture for laying hens. The labelling of the lysine N in the wheat was 13.58 atom-%, that of histidine N 14.38 and that of arginine 15N' 13.63 atom-% 15N'. Three hens each were butchered 12, 36, 60 and 108 h after the last 15N' feeding. The first three hens did not receive any feed before being butchered. The following three hens each received the unlabelled feed ration for another 1, 2 or 4 days, resp., after the main period until they were butchered. The total of skeleton muscles, heart and stomach muscle (without inner skin) of each hen were combined into one sample, cut thinly, drenched with fluid nitrogen and pulverized. N, 15N' and the basic and non-basic amino acids as well as their 15N' were determined in the individual samples. In contrast to the organs, the proteins in the muscle tissue have a long half-life so that a slight decrease of atom-% 15N' in the muscles could only be detected after 108 h. The 14N and 15N' quota of the non-basic amino acids in the total nitrogen of the muscles is 50 %. The 14N quota of the basic amino acids is 30% and the 15N' quota only 22.5% in the total muscle N. The heavy nitrogen of the free lysine in the TCA soluble N fraction is hardly detectable 36 h and 60 h after the last 15N' supply and not at all after 108 h. In contrast to this, the other two free basic amino acids remain significantly higher labelled in dependence on the last butchering time. (author)

  2. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 2

    International Nuclear Information System (INIS)

    Over 4 days 12 colostomized laying hens received toghether with a commercial ration labelled wheat with a 15N excess (15N') of 14.37 atom-%. The labelling of the basic amino acids amounted to 13.58 atom-% for lysine, to 14.38 atom-% for histidine and to 13.63 atom-% 15N' for arginine. 3 animals each were butchered 12 h, 36 h, 60 h and 108 h, resp. after the last application of 15N. The heavy nitrogen in the total N and in the N fraction of non-protein origin as well as in the basic amino acids in feces was daily determined for the individual hens in the total experimental period. On average the crude protein of feces contained 5.45% lysine, 2.32% histidine and 3.68% arginine: the protein of feces correspondingly contained 5.43% lysine, 2.32% histidine and 4.07% arginine. The quota of TCA-soluble N in the total N of feces amounts to one third on the 3rd and 4th days of the experiment and that of 15N' to 28%. The average atom-% 15N' of the protein fraction is 3.48 atom-% 15N' and that of the non-protein N fraction of feces 2.93 atom-% 15N'. The apparent digestibility of the 14N of the ration on average amounts to 82.8% and that of the wheat 15N' to 87.5%. The average quota of the basic amino acids in the protein compounds of feces amounts to 70.9% for lysine 15N', 73.7% for histidine 15N' and 70.3% for arginine 15N'. The digestibility of the 15N-labelled amino acids amounts to 80.4% for lysine, 90.8% for histidine and 90.2% for arginine. (author)

  3. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 4

    International Nuclear Information System (INIS)

    12 colostomized laying hybrids with an 81% laying performance received 36 g wheat containing a 15N excess (15N') of 14.37 atom-% in a customary ration over 4 days. The wheat lysine contained 13.58 atom-% 15N', histidine 14.38 and arginine 13.63 atom-% 15N'. In the 4-day period of 15N' application 540 mg 15N', 18.1 mg lysine 15N', 21.5 mg histidine 15N' and 47.9 mg arginine 15N' were consumed per hen. Subsequently the animals received the same ration with unlabelled wheat. 12 h, 36 h, 60 h and 108 h after the last 15N' application 3 animals each were butchered. The atom-% 15N' of the lysine was below that of the two other basic and of the non-basic amino acids. The labelling of the amino acids of the egg white decreased rapidly 2 days after 15N' application. The atom-% of the 15N' of the yolk of egg, however, increased after the discontinuation and remained the same for 4 days after the last 15N' application. The 14N and 15N' amounts measured in the complete experiment period are distributed over the 3 basic and the 12 non-basic (excluding thioamino acids) amino acids in the white of egg for 14N as 25.0%:57.6% and for 15N' as 18.2%:57.5%. In the yolk of egg 28.5% 14N for the basic and 56.8% for the non-basic amino acids could be calculated; the corresponding values for 15N' were 17.8% and 55.5%. (author)

  4. Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

    Science.gov (United States)

    Wang, Qiu-Yi; Song, Yong; Huang, Wei; Xiao, Li; Wang, Qiu-Shi; Feng, Gui-Mei

    2016-01-01

    Background: While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Methods: Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial. Participants were randomized into two groups such as DRP-containing COCs, and CPA-containing COCs. Participants took COCs cyclically for 6 months, combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise). Clinical measures and biochemical and hormone profiles were compared. Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests. The Wilcoxon signed rank test was used when the data were not normally distributed. Analysis of covariance was used to control for age, body mass index (BMI), and baseline data of each analyzed parameter when compared between the two groups. Results: A total of 68 patients have completed the study. The combination regimen of COCs, metformin, and lifestyle modifications in these patients resulted in a significant decrease in BMI, acne, and hirsutism scores when compared to baseline levels in both groups (P PCOS and metabolic disorders compared with CPA-containing COCs. Trial Registration: Chinese Clinical Trial Registry, ChiCTR-TRC-11001143; http://www.chictr.org.cn/showproj.aspx?proj=8395. PMID:27064030

  5. Inborn errors of metabolism underlying primary immunodeficiencies.

    Science.gov (United States)

    Parvaneh, Nima; Quartier, Pierre; Rostami, Parastoo; Casanova, Jean-Laurent; de Lonlay, Pascale

    2014-10-01

    A number of inborn errors of metabolism (IEM) have been shown to result in predominantly immunologic phenotypes, manifesting in part as inborn errors of immunity. These phenotypes are mostly caused by defects that affect the (i) quality or quantity of essential structural building blocks (e.g., nucleic acids, and amino acids), (ii) cellular energy economy (e.g., glucose metabolism), (iii) post-translational protein modification (e.g., glycosylation) or (iv) mitochondrial function. Presenting as multisystemic defects, they also affect innate or adaptive immunity, or both, and display various types of immune dysregulation. Specific and potentially curative therapies are available for some of these diseases, whereas targeted treatments capable of inducing clinical remission are available for others. We will herein review the pathogenesis, diagnosis, and treatment of primary immunodeficiencies (PIDs) due to underlying metabolic disorders.

  6. In Ovo administration of silver nanoparticles and/or amino acids influence metabolism and immune gene expression in chicken embryos

    DEFF Research Database (Denmark)

    Bhanja, Subrat K.; Hotowy, Anna Malgorzata; Mehra, Manish;

    2015-01-01

    Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers...... but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control...... embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, Nano...

  7. Metabolic enzymes link morphine withdrawal with metabolic disorder

    Institute of Scientific and Technical Information of China (English)

    Xi Jiang; Jing Li; Lan Ma

    2007-01-01

    @@ Energy metabolism is a fundamental biological process that is vital for the survival of all species. Disorders in the metabolic system result in deficiency or redundancy of certain nutrients, including carbohydrates, lipids, amino acids, etc. Abnormality of the energy metabolism system leads to a number of metabolic diseases, such as the metabolic syndrome. Broadly speaking, the term "metabolic diseases" now tends to be widened to the category that refers to all diseases with metabolism disorder.

  8. Enhanced antibody production associated with altered amino acid metabolism in a hybridoma high-density perfusion culture established by gravity separation.

    Science.gov (United States)

    Hansen, H A; Damgaard, B; Emborg, C

    1993-01-01

    A high density hybridoma perfusion culture was established by separating and recycling cells from the product stream to the reactor using a simple external sedimentation-based separator-an inclined modified Erlenmeyer flask. After 3 weeks, when the optimal perfusion rate of 1.0 day-1 had been reached, viable cell density stabilized at around 10 x 10(6) cells ml-1, a level five times that obtained by simple batch culture. The efficiency of the separator was enhanced by cell flocculation. Specific antibody productivity, which was initially 0.4 micrograms 1 x 10(6) cells-1 h-1, decreased to half that value while cell density was increasing, but recovered to the initial level when the culture finally stabilized at a high cell density. During the final phase, when viable cell density and specific antibody production were high, there was a marked shift in metabolism. Consumption of the two most important substrates for energy generation, glucose and glutamine, caused their broth concentrations to decrease to 1.5 mM and 1 mM, respectively, from input medium concentrations of 25 mM and 10 mM, respectively. At the same time there was an increase in the specific production of glycine and aspartate, their broth concentrations reaching 1.5 mM and 0.02 mM, respectively. We suggest that this shift in metabolism results in enhanced production of ATP from glutamine. The specific glucose consumption and lactate production also indicate that there is a shift to more energy efficient metabolism. The mechanism whereby this leads to enhanced specific antibody production remains to be elucidated. Nevertheless, the combination of high cell density and enhanced productivity obtained with the present perfusion culture resulted in a high monoclonal antibody production-100 mg 1-1 d-1. PMID:7763691

  9. An enhanced in vivo stable isotope labeling by amino acids in cell culture (SILAC) model for quantification of drug metabolism enzymes.

    Science.gov (United States)

    MacLeod, A Kenneth; Fallon, Padraic G; Sharp, Sheila; Henderson, Colin J; Wolf, C Roland; Huang, Jeffrey T-J

    2015-03-01

    Many of the enzymes involved in xenobiotic metabolism are maintained at a low basal level and are only synthesized in response to activation of upstream sensor/effector proteins. This induction can have implications in a variety of contexts, particularly during the study of the pharmacokinetics, pharmacodynamics, and drug-drug interaction profile of a candidate therapeutic compound. Previously, we combined in vivo SILAC material with a targeted high resolution single ion monitoring (tHR/SIM) LC-MS/MS approach for quantification of 197 peptide pairs, representing 51 drug metabolism enzymes (DME), in mouse liver. However, as important enzymes (for example, cytochromes P450 (Cyp) of the 1a and 2b subfamilies) are maintained at low or undetectable levels in the liver of unstimulated metabolically labeled mice, quantification of these proteins was unreliable. In the present study, we induced DME expression in labeled mice through synchronous ligand-mediated activation of multiple upstream nuclear receptors, thereby enhancing signals for proteins including Cyps 1a, 2a, 2b, 2c, and 3a. With this enhancement, 115 unique, lysine-containing, Cyp-derived peptides were detected in the liver of a single animal, as opposed to 56 in a pooled sample from three uninduced animals. A total of 386 peptide pairs were quantified by tHR/SIM, representing 68 Phase I, 30 Phase II, and eight control proteins. This method was employed to quantify changes in DME expression in the hepatic cytochrome P450 reductase null (HRN) mouse. We observed compensatory induction of several enzymes, including Cyps 2b10, 2c29, 2c37, 2c54, 2c55, 2e1, 3a11, and 3a13, carboxylesterase (Ces) 2a, and glutathione S-transferases (Gst) m2 and m3, along with down-regulation of hydroxysteroid dehydrogenases (Hsd) 11b1 and 17b6. Using DME-enhanced in vivo SILAC material with tHR/SIM, therefore, permits the robust analysis of multiple DME of importance to xenobiotic metabolism, with improved utility for the study of

  10. 6th Amino Acid Assessment Workshop

    Science.gov (United States)

    The focus of the 6th workshop is on lysine, arginine, and related amino acids. Functions, metabolic pathways, clinical uses, and upper tolerance intakes are emphasized in the articles that follow. Lysine is arguably the most deficient amino acid in the food supply of countries where poverty exists, ...

  11. Dietary glutamine supplementation effects on amino acid metabolism, intestinal nutrient absorption capacity and antioxidant response of gilthead sea bream (Sparus aurata) juveniles.

    Science.gov (United States)

    Coutinho, F; Castro, C; Rufino-Palomares, E; Ordóñez-Grande, B; Gallardo, M A; Oliva-Teles, A; Peres, H

    2016-01-01

    A study was undertaken to evaluate dietary glutamine supplementation effects on gilthead sea bream performance, intestinal nutrient absorption capacity, hepatic and intestinal glutamine metabolism and oxidative status. For that purpose gilthead sea bream juveniles (mean weight 13.0g) were fed four isolipidic (18% lipid) and isonitrogenous (43% protein) diets supplemented with 0, 0.5, 1 and 2% glutamine for 6weeks. Fish performance, body composition and intestinal nutrient absorption capacity were not affected by dietary glutamine levels. Hepatic and intestinal glutaminase (GlNase), glutamine synthetase (GSase), alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were also unaffected by dietary glutamine supplementation. In the intestine GlNase activity was higher and GSase/GlNase ratio was two-fold lower than in the liver, suggesting a higher use of glutamine for energy production by the intestine than by the liver. The liver showed higher catalase and glucose-6-phosphate dehydrogenase activities, while the intestine presented higher glutathione peroxidase and glutathione reductase activities and oxidised glutathione content, which seems to reveal a higher glutathione dependency of the intestinal antioxidant response. Total and reduced glutathione contents in liver and intestine and superoxide dismutase activity in the intestine were enhanced by dietary glutamine, though lipid peroxidation values were not affected. Overall, differences between liver and intestine glutamine metabolism and antioxidant response were identified and the potential of dietary glutamine supplementation to gilthead sea bream's antioxidant response was elucidated.

  12. Postprandial fate of amino acids: adaptation to molecular forms

    OpenAIRE

    Nolles, J.A.

    2006-01-01

    During the postprandial phase dietary proteins are digested to peptides and amino acids and absorbed. Once absorbed the peptides are further hydrolyzed to amino acids and transported to the tissues. These amino acids are largely incorporated into body proteins. Not all amino acids are, however, incorporated into body proteins part of these amino acids are oxidized, and can, thus, no longer be utilized to support protein metabolism in the body. The objective of this thesis was to increase the ...

  13. Chemical modification of L-glutamine to alpha-amino glutarimide on autoclaving facilitates Agrobacterium infection of host and non-host plants: A new use of a known compound

    Directory of Open Access Journals (Sweden)

    Das Pralay

    2011-05-01

    Full Text Available Abstract Background Accidental autoclaving of L-glutamine was found to facilitate the Agrobacterium infection of a non host plant like tea in an earlier study. In the present communication, we elucidate the structural changes in L-glutamine due to autoclaving and also confirm the role of heat transformed L-glutamine in Agrobacterium mediated genetic transformation of host/non host plants. Results When autoclaved at 121°C and 15 psi for 20 or 40 min, L-glutamine was structurally modified into 5-oxo proline and 3-amino glutarimide (α-amino glutarimide, respectively. Of the two autoclaved products, only α-amino glutarimide facilitated Agrobacterium infection of a number of resistant to susceptible plants. However, the compound did not have any vir gene inducing property. Conclusions We report a one pot autoclave process for the synthesis of 5-oxo proline and α-amino glutarimide from L-glutamine. Xenobiotic detoxifying property of α-amino glutarimide is also proposed.

  14. Dynamics of the amino acid and protein metabolism of laying hens after the application of 15N-labelled wheat protein. 5

    International Nuclear Information System (INIS)

    12 colostomized laying hens which received 15N-labelled wheat over 4 days were butchered 12 h, 36 h, and 108 h (3 animals each) after the last 15N application. The intake of 15N exess (15N') from the wheat amounted to 540 mg 15N' during the application period. The 15N' in the blood plasma decreased after the last 15N' application from 0.76 atom-% to 0.55 atom-% after 108 h, the labelling of the corpuscular components at the same measuring points increased from 0.28 to 0.50 atom-% 15N'. 96.6% of the plasma 15N' and 93,8% of that in the corpuscles is precipitable in trichloroacetic acid. The atom-% 15N' of histidine in the total blood remained unchanged in dependence on the butchering time. The 15N amount in lysine and arginine and that in the non-basic amino acids decreased inconsiderably in the period between 12 h and 108 h after the last 15N' wheat feeding. (author)

  15. 2-Oxoglutarate: linking TCA cycle function with amino acid, glucosinolate, flavonoid, alkaloid and gibberellin biosynthesis

    Directory of Open Access Journals (Sweden)

    Wagner L. Araújo

    2014-10-01

    Full Text Available The tricarboxylic acid (TCA cycle intermediate 2-oxoglutarate (2-OG is used as an obligatory substrate in a range of oxidative reactions catalyzed by 2-OG-dependent dioxygenases. These enzymes are widespread in nature being involved in several important biochemical processes. We have recently demonstrated that tomato plants in which the TCA cycle enzyme 2-OG dehydrogenase (2-ODD was antisense inhibited were characterized by early senescence and modified fruit ripening associated with differences in the levels of bioactive gibberellin (GA. Accordingly, there is now compelling evidence that the TCA cycle plays an important role in modulating the rate of flux from 2-OG to amino acid metabolism. Here we discuss recent advances in the biochemistry and molecular biology of 2-OG metabolism occurring in different biological systems indicating the importance of 2-OG and 2-OG dependent dioxygenases not only in glucosinolate, flavonoid and alkaloid metabolism but also in GA and amino acid metabolism. We additionally summarize recent findings regarding the impact of modification of 2-OG metabolism on biosynthetic pathways involving 2-ODDs.

  16. Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment

    Science.gov (United States)

    Hu, Hong; Bai, Xi; Shah, Assar Ali; Dai, Sifa; Wang, Like; Hua, Jinling; Che, Chuanyan; He, Shaojun; Wen, Aiyou; Jiang, Jinpeng

    2016-06-01

    The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased ( P glutamine synthetase (GS) and gamma-aminobutyric acid transaminase (GABA-T) at 28, 35, and 42 days. Dietary Gln and GABA improved ( P < 0.05) DWG and DFC of broilers under cyclic HS during 28-42 days. In breast muscle, the Gln supplementation increased ( P < 0.05) the concentrations of Gln (28, 35, and 42 days), Glu (28, 35, and 42 days), and GABA (42 days) and the activities of glutaminase (28, 35, and 42 days) and GAD (28, 35, and 42 days) but decreased ( P < 0.05) GS activities at 28, 35, and 42 days and GABA-T activities at 28 days. The addition of GABA increased ( P < 0.05) the concentrations of Gln and Glu and activities of glutaminase and GAD, while it decreased ( P < 0.05) GABA-T activities at 28, 35, and 42 days. Significant interactions ( P < 0.05) between Gln and GABA were found on breast skeletal muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA metabolism of broilers.

  17. Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors

    Directory of Open Access Journals (Sweden)

    Naoyuki eSato

    2013-11-01

    Full Text Available It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD. Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of 1 compromised vascular reactivity, 2 vascular lesions, 3 hypo/hyperglycemia, and 4 exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. Beta-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: 1 functional MRI or SPECT for cerebrovascular reactivity, 2 MRI for ischemic lesions and atrophy, 3 clinical episodes of hypoglycemia and hyperglycemia, 4 amyloid-PET and tau-PET for pathological features of AD, would be required.

  18. Metabolic microspheres

    Science.gov (United States)

    Fox, Sidney W.

    1980-08-01

    A systematic review of catalytic activities in thermal proteinoids and microspheres aggregated therefrom yields some new inferences on the origins and evolution of metabolism. Experiments suggest that, instead of being inert, protocells were already biochemically and cytophysically competent. The emergence and refinement of metabolism ab initio is thus partly traced conceptually. When the principle of molecular self-instruction, as of amino acids in peptide synthesis, is taken into account as a concomitant of natural selection, an expanded theory of organismic evolution, including saltations, emerges.

  19. Comparison of Drospirenone-with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

    Institute of Scientific and Technical Information of China (English)

    Qiu-Yi Wang; Yong Song; Wei Huang; Li Xiao; Qiu-Shi Wang; Gui-Mei Feng

    2016-01-01

    Background:While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS),comparative data regarding metabolic effects of different progestogens on this patient population are missing.This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs,combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders.Methods:Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial.Participants were randomized into two groups such as DRP-containing COCs,and CPA-containing COCs.Participants took COCs cyclically for 6 months,combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise).Clinical measures and biochemical and hormone profiles were compared.Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests.The Wilcoxon signed rank test was used when the data were not normally distributed.Analysis of covariance was used to control for age,body mass index (BMI),and baseline data of each analyzed parameter when compared between the two groups.Results:A total of 68 patients have completed the study.The combination regimen of COCs,metformin,and lifestyle modifications in these patients resulted in a significant decrease in BMI,acne,and hirsutism scores when compared to baseline levels in both groups (P < 0.05).Blood pressure (BP) was significantly different in the CPA group when compared to baseline (75.14 ± 6.77 mmHg vs.80.70 ± 5.60 mmHg,P < 0.01),and after 6 months of treatment,only the change in systolic BP was significantly different between the two groups (4.00 [-6.00,13.00] mmHg vs.-3.50 [-13.00,9.00] mmHg,P =0.009).Fasting glucose,fasting insulin,and homeostasis model assessment-insulin resistance decreased significantly in the DRP group (5.40 ± 0.41 mmol

  20. Modification of the liver fatty acids by Hibiscus sabdariffa Linnaeus (Malvaceae) infusion, its possible effect on vascular reactivity in a metabolic syndrome model.

    Science.gov (United States)

    Pérez-Torres, Israel; Zúñiga Muñoz, Alejandra; Beltrán-Rodríguez, Ulises; Díaz-Díaz, Eulises; Martínez-Memije, Raúl; Guarner Lans, Verónica

    2014-01-01

    We investigated the effects of Hibiscus sabdariffa Linnaeus (HSL)-fed infusion on the fatty acid (FA) profile in liver of metabolic syndrome (MS) rats and its possible effect on vascular reactivity. Body mass, intra-abdominal fat, triglycerides, insulin, blood pressure, saturated, monounsaturated FA, NEFAs, Δ(9)-, Δ(6)-desaturases and vasoconstriction were increased, while vasorelaxation, polyunsaturated FA, endothelial nitric oxide and [Formula: see text]/[Formula: see text] ratio decreased in MS versus Control, but HSL infusion modified it and increased Δ(5)-desaturase. The results suggest that the alteration in FA liver metabolism in the MS contributes to impaired vascular reactivity, but treatment with of HSL infusion can improve this condition. PMID:23734849

  1. Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription

    OpenAIRE

    Allison, David F.; Wamsley, J. Jacob; Kumar, Manish; Li, Duo; Gray, Lisa G.; Hart, Gerald W.; David R Jones; Mayo, Marty W.

    2012-01-01

    The molecular mechanisms linking glucose metabolism with active transcription remain undercharacterized in mammalian cells. Using nuclear factor-κB (NF-κB) as a glucose-responsive transcription factor, we show that cells use the hexosamine biosynthesis pathway and O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) to potentiate gene expression in response to tumor necrosis factor (TNF) or etoposide. Chromatin immunoprecipitation assays demonstrate that, upon induction, OGT localizes ...

  2. Selective posttranslational modification of phage-displayed polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, Meng-Lin; Tian, Feng; Schultz, Peter

    2013-11-19

    The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2] cycloaddition reactions and Staudinger modifications.

  3. Selective posttranslational modification of phage-displayed polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, Meng-Lin; Tian, Feng; Schultz, Peter

    2013-02-05

    The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2]cycloaddition reactions and Staudinger modifications.

  4. Plasma amino acids

    Science.gov (United States)

    Plasma amino acids is a screening test done on infants that looks at the amounts of amino ... Laboratory error High or low amounts of individual plasma amino acids must be considered with other information. ...

  5. Plasma amino acids

    Science.gov (United States)

    Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

  6. Amino acids attached to 2'-amino-LNA: Synthesis of DNA mixmer oligonucleotides with increased duplex stability

    DEFF Research Database (Denmark)

    Johannsen, Marie Willaing; Wengel, Jesper; Wamberg, Michael Chr.;

    2010-01-01

    The synthesis of 2'-amino-LNA (locked nucleic acid) opens up exciting possibilities for modification of nucleic acids by conjugation to the 2'-nitrogen. Incorporation of unmodified and N-functionalized 2'-amino-LNA nucleotides improve duplex stability compared to unmodified DNA. 2'-Amino......-LNA nucleosides derivatized with amino acids have been synthesized and incorporated into DNA oligonucleotides. Following oligonucleotide synthesis, peptides have been added using solid phase peptide coupling chem. Modification of oligonucleotides with pos. charged residues greatly improves thermal stability....

  7. Methods for Studying Wnt Protein Modifications/Inactivations by Extracellular Enzymes, Tiki and Notum.

    Science.gov (United States)

    Zhang, Xinjun; He, Xi

    2016-01-01

    Wnt proteins are modified and inactivated by two extracellular enzymatic antagonists, Tiki and Notum. Tiki proteins act as membrane-tethered metalloproteases to cleave a fragment from the amino terminus of Wnt proteins. Notum is a Wnt deacylase that removes the lipid modification that is essential for Wnt activities. Here, we provide detailed procedures for preparing enzymatic active Tiki and Notum proteins and the in vitro enzymatic reactions. We also describe a metabolic labeling and click chemistry method for detection of Wnt protein acylation. PMID:27590149

  8. 表观遗传修饰在糖尿病代谢记忆中的作用%The role of epigenetic modification in diabetic metabolic memory

    Institute of Scientific and Technical Information of China (English)

    朱汉钢; 陈璐璐; 廖云飞

    2012-01-01

    糖尿病患者在血糖得到控制后,糖尿病并发症仍然持续发展的现象提示了以前暴露于高血糖导致的“代谢记忆”.近来的研究提示“代谢记忆”可能归因于靶细胞的表观遗传改变.许多实验证据显示:组蛋白乙酰基转移酶(HATs)、组蛋白去乙酰化酶(HDACs)、组蛋白甲基转移酶(HMTs)、组蛋白赖氨酸去甲基化酶(KDMs)以及microRNA在调节几种与糖尿病并发症相关的关键基因表观遗传修饰中发挥了重要作用.进一步阐明表观遗传修饰在糖尿病“代谢记忆”中的作用机制以及明确相应的细胞信号通路,对于糖尿病及其并发症的防治有重要意义.%It is evident that metabolic memory,whereby diabetic complications continue to develop and progress in individuals who returned to normal glycemic control after a period of transient hyperglycemia,has long lasting effects.Recent studies suggest that “metabolic memory” may be due to epigenetic changes in target oells.Understanding the molecular changes in chromatin structure and the functional relationship with altered signaling pathways is now considered to represent an important conceptual challenge to explain diabetes and the phenomenon of metabolic memory.Emerging evidences indicate that critical gene-activating epigenetic changes may confer future cell memories. Many experimental evidences show that histone acetyltransferases (HATs), histone deacetylases (HDACs),histone methyltransferases (HMTs),histone lysine demethylases (KDMs),and microRNAs play important roles in the epigenetic changes of several key genes related to diabetic complications. Transient hyperglycemia promotes gene-activating epigenetic changes and signaling events critical in the development and progression of diabetic vascular complications.Further characterisation of these glucose-induced epigenetic events and the identification of key enzymes involved will help us to develop new therapeutic strategies for

  9. Effect of intraoperative amino acid infusion on glucose metabolism in dogs%术中静脉输注氨基酸对犬糖代谢的影响

    Institute of Scientific and Technical Information of China (English)

    金琳; 葛圣金; 薛张纲

    2008-01-01

    Objective To investigate the effect of intraoperative amino acid infusion on perioperative glucose metabolism. Methods Thirty-six adult mongrel dogs of both sexes weighing 12-16 kg undergoing partially small intestine resection under general anesthesia were randomly allocated to one of 4 groups (n=9 each): Ⅰ control group received normal saline (C);Ⅱ,Ⅲ,Ⅳ amino acid group (A1, A2, A3) received iv infusion of 2.85%, 5.70% and 11.4% 18-amino acid respectively at 12 ml·kg-1·h-1 during operation starting from skin incision until the end of operation. The animals were premedicated with ketamine and diazepam. Anesthesia was induced with propofol 5-10 mg/kg, fentanyl 2 μg/kg and vecuronium 0.2 mg/kg and maintained with 1%-3% isoflurane and intermittent iv boluses of fentanyl and vecuronium. The animals were intubated and mechanically ventilated. PET CO2 was maintained at 30-40 mm Hg. ECG, MAP, HR, PET CO2 and esophageal T0 were continuously monitored. Venous blood samples were collected before anesthesia (T1), 15 min after induction of anesthesia (T2), 15, 30 min and 1 h after skin incision (T3-5), when abdomen was closed (T6) and 1,2,4,8 and 24 h after operation (T7-11) for determination of plasma glucose, lactate, insulin and glucagon. Liver biopsy was performed at T6-11 and muscle biopsy at T2,6,11 for measurement of hepatic and muscle glucagon. Homa index was used to estimate the degree of insulin resistance. Results The plasma glucose and insulin concentrations were significantly increased at T3-11 as compared with the baseline at T1 in all 4 groups (P<0.05). The plasma insulin concentrations were significantly higher in group A1 (at T6), group A2 (at T3,6) and group A3 (at T3-11) than in group C (P<0.05). Homa index was significantly higher in group A3(at T3-8) than in group C. Conclusion Intraoperative amino acid infusion increases plasma insulin concentration but does not prevent glycogenolysis especially high dose amino acid infusion.%目的 探讨术

  10. Adsorption Properties of Amino Acids on Ca/SBA-15 Prepared by Calcium Modification under Microwave Radiation%氨基酸在微波辅助钙改性SBA-15上的吸附性能

    Institute of Scientific and Technical Information of China (English)

    张三山; 张德喜; 肖建国; 刘亚纯; 伏再辉

    2012-01-01

    The calcium modified SBA-15 materials, denoted as Ca / SBA-15 ( MW ) , were prepared by solid-phase method under microwave radiation. The structure of the materials was characterized by small angle XRD, N2 adsorption-desorption, and TEM. Adsorption performance of four typical amino acids on Ca/SBA-15( MW) was studied. Effects of the. calcium loading and pH of amino acid solution on the adsorption performance were investigated. The results show that the calcium modified materials prepared by this method still retain similar structural characteristics of SBA-15, and calcium species are uniformly dispersed in the mesoporous material pore channel. Ca/ SBA-15 (MW) displays better adsorption ability to the adsorption of acidic glutamic acid at pH = 2.0 - 10 as compared to pure silicon SBA-15. Moreover, their adsorption capacity is proportional to calcium content of the samples. For the adsorption of basic amino acid lysine( Lys) , Ca/SBA-15 ( MW) shows the weaker adsorption ability at pH < 10 compared with SBA-15, whereas its adsoiption ability is stronger than that of SBA-15 when the pH value of adsorption solution was adjusted to 10. For the adsorption of some neutral amino acids such as phenylalanine and alanine on SBA-15, their adsorption amount was low at pH =2. 0 ~6. 0 and pH =6. 0 ~ 10. When pH value was ca. 6.0, the maximum adsorption amount of phenylalanine and alanine over SBA-15 was up to 0. 34 and 0. 17 mmol/g, respectively. Ca/SBA-15 ( MW) exhibits a weak adsorption capacity to alanine, and hardly adsorbed phenylalanine. This is likely due to the surface hydrophilicity of the calcium-containing samples, which can lead to a poor adsorption interaction with hydrophobic alanine and especially phenylalanine.%采用微波辐射固相法制备了钙改性SBA-15材料Ca/SBA-15 (MW),借助小角XRD、N2吸附-脱附实验及TEM表征了Ca/SBA-15 (MW)的结构,研究了4种典型的氨基酸在Ca/SBA- 15 (MW)上的吸附性能,并考察了钙负载量和pH值对其

  11. Experiment K-6-21. Effect of microgravity on 1) metabolic enzymes of type 1 and type 2 muscle fibers and on 2) metabolic enzymes, neutransmitter amino acids, and neurotransmitter associated enzymes in motor and somatosensory cerebral cortex. Part 1: Metabolic enzymes of individual muscle fibers; part 2: metabolic enzymes of hippocampus and spinal cord

    Science.gov (United States)

    Lowry, O.; Mcdougal, D., Jr.; Nemeth, Patti M.; Maggie, M.-Y. Chi; Pusateri, M.; Carter, J.; Manchester, J.; Norris, Beverly; Krasnov, I.

    1990-01-01

    The individual fibers of any individual muscle vary greatly in enzyme composition, a fact which is obscured when enzyme levels of a whole muscle are measured. The purpose of this study was therefore to assess the changes due to weightless on the enzyme patterns composed by the individual fibers within the flight muscles. In spite of the limitation in numbers of muscles examined, it is apparent that: (1) that the size of individual fibers (i.e., their dry weight) was reduced about a third, (2) that this loss in dry mass was accompanied by changes in the eight enzymes studied, and (3) that these changes were different for the two muscles, and different for the two enzyme groups. In the soleus muscle the absolute amounts of the three enzymes of oxidative metabolism decreased about in proportion to the dry weight loss, so that their concentration in the atrophic fibers was almost unchanged. In contrast, there was little loss among the four enzymes of glycogenolysis - glycolysis so that their concentrations were substantially increased in the atrophic fibers. In the TA muscle, these seven enzymes were affected in just the opposite direction. There appeared to be no absolute loss among the oxidative enzymes, whereas the glycogenolytic enzymes were reduced by nearly half, so that the concentrations of the first metabolic group were increased within the atrophic fibers and the concentrations of the second group were only marginally decreased. The behavior of hexokinase was exceptional in that it did not decrease in absolute terms in either type of muscle and probably increased as much as 50 percent in soleus. Thus, their was a large increase in concentration of this enzyme in the atrophied fibers of both muscles. Another clear-cut finding was the large increase in the range of activities of the glycolytic enzymes among individual fibers of TA muscles. This was due to the emergence of TA fibers with activities for enzymes of this group extending down to levels as low as

  12. 基于柱前衍生-超高效液相色谱-质谱联用技术的植物提取液中氨基化合物代谢谱分析%Metabolic profiling analysis of amino metabolites in plant extract based on pre-column derivatization-ultra high performance liquid chromatography-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    张俊杰; 赵春霞; 赵燕妮; 赵洁妤; 李丽丽; 路鑫; 许国旺

    2015-01-01

    Amino metabolites are important compounds that play a key role in plant growth and development. A metabolic profiling analysis method of amino metabolites in plant extract was developed based on pre-column derivatization-ultra high performance liquid chromatography-mass spectrometry. Using the tobacco leaf as an example,a total of 87 amino metabolites, including amino acids,amines,peptides,alkaloids etc. were detected. The repeatability of the method was good with RSDs of 85 amino metabolites between 1. 5% and 18. 8%. Forty-three amino metabolites validated by standard samples showed good linearity with the correlation coefficients of 0. 993-0. 999,covered linear range of four orders of magnitude. The limits of detection were 0. 03-6. 58 ng/mL. The intra-day and inter-day precisions were 0. 7%-15. 6% and 0. 8%-22. 9%,respectively. The recoveries were 74. 4%-122. 7%. The influence of topping on metabolic profiling of amino metabolites in fresh tobacco was investigated using the developed method. The results showed that the amino metabolites in the upper tobacco leaves were most affected than those in the middle and lower leaves. Metabolism of amino metabolites in the upper leaves after topping was mainly towards the alkaloid synthesis. The method integrated the advantages of triple quadrupole mass spectrometry and high resolution quadrupole-time of flight mass spectrometry. It can be used for metabolic profiling analysis of amino metabolites in plant extract with high sensitivity and selectivity.%氨基化合物在植物生长发育中起着重要作用。本文建立了一种基于柱前衍生-超高效液相色谱-质谱联用技术的植物提取液中氨基化合物代谢谱的分析方法。以烟草鲜叶为例,共检测出87种氨基化合物。其中43种氨基化合物的定量分析结果表明,方法的线性相关系数在0.993~0.999之间,线性范围可达到4个数量级,检出限为0.03~6.58 ng/mL,日内、日间精密度分别为0.7

  13. Surface Modification for Microreactor Fabrication

    OpenAIRE

    Wladyslaw Torbicz; Jerzy Kruk; Konrad Dudziński; Roberto Canteri; Michele Vendano; Lorenzo Lunelli; Cecilia Pederzolli; Elżbieta Remiszewska; Pijanowska, Dorota G.

    2006-01-01

    In this paper, methods of surface modification of different supports, i.e. glass and polymeric beads for enzyme immobilisation are described. The developed method of enzyme immobilisation is based on Schiff's base formation between the amino groups on the enzyme surface and the aldehyde groups on the chemically modified surface of the supports. The surface of silicon modified by APTS and GOPS with immobilised enzyme was characterised by atomic force microscopy (AFM), time-of-flight secondary ...

  14. The Effect of UDP-glucuronosyltransferase 1A1 Expression on the Mutagenicity and Metabolism of the Cooked-Food Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4-5,b]pyridine in CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Malfatti, M A; Wu, R W; Felton, J S

    2004-08-13

    UDP-glucuronosyltransferase proteins (UGT) catalyze the glucuronidation of both endogenous and xenobiotic compounds. In previous studies UGT1A1 has been implicated in the detoxification of certain food-borne-carcinogenic-heterocyclic amines. To determine the importance of UDP-glucuronosyltransferase 1A1 (UGT1A1) in the biotransformation of the cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), genetically modified CHO cells that are nucleotide excision repair-deficient, and express cytochrome P4501A2 (UV5P3 cell line) were transfected with a cDNA plasmid of human UGT1A1 to establish the UDPglucuronosyltransferase 1A1 expressing 5P3hUGT1A1 cell line. Expression of the UGT1A1 gene was verified by screening neogene expressing clonal isolates (G-418 resistant) for their sensitivity to cell killing from PhIP exposure. Five of eleven clones were chosen for further analysis due to their resistance to cell killing. Western blot analysis was used to confirm the presence of the UGT1A1 and CYP1A2 proteins. All five clones displayed a 52 kDa protein band, which corresponded to a UGT1A1 control protein. Only four of the clones had a protein band that corresponded to the CYP1A2 control protein. Correct fragment size of the cDNAs in the remaining 4 clones was confirmed by RT-PCR and quantification of the mRNA product was accomplished by real-time RT-PCR. Expression of UGT1A1 in the transfected cells was 10{sup 4}-10{sup 5} fold higher relative to the UV5P3 parental cells. One clone (No.14) had a 10 fold higher increase in expression at 1.47 x 10{sup 5} over the other three clones. This clone was also the most active in converting N-hydroxy-PhIP to N-hydroxy-PhIP glucuronide conjugates in microsomal metabolism assays. Based on the D{sub 50} values, the cytotoxic effect of PhIP was decreased {approx}350 fold in the 5P3hUGT1A1 cells compared to the UV5P3 control cells. In addition no significant increase in mutation frequency was observed in the

  15. Human Protein and Amino Acid Requirements.

    Science.gov (United States)

    Hoffer, L John

    2016-05-01

    Human protein and amino acid nutrition encompasses a wide, complex, frequently misunderstood, and often contentious area of clinical research and practice. This tutorial explains the basic biochemical and physiologic principles that underlie our current understanding of protein and amino acid nutrition. The following topics are discussed: (1) the identity, measurement, and essentiality of nutritional proteins; (2) the definition and determination of minimum requirements; (3) nutrition adaptation; (4) obligatory nitrogen excretion and the minimum protein requirement; (5) minimum versus optimum protein intakes; (6) metabolic responses to surfeit and deficient protein intakes; (7) body composition and protein requirements; (8) labile protein; (9) N balance; (10) the principles of protein and amino acid turnover, including an analysis of the controversial indicator amino acid oxidation technique; (11) general guidelines for evaluating protein turnover articles; (12) amino acid turnover versus clearance; (13) the protein content of hydrated amino acid solutions; (14) protein requirements in special situations, including protein-catabolic critical illness; (15) amino acid supplements and additives, including monosodium glutamate and glutamine; and (16) a perspective on the future of protein and amino acid nutrition research. In addition to providing practical information, this tutorial aims to demonstrate the importance of rigorous physiologic reasoning, stimulate intellectual curiosity, and encourage fresh ideas in this dynamic area of human nutrition. In general, references are provided only for topics that are not well covered in modern textbooks. PMID:26796095

  16. Laser modification of polyamide fabrics

    Science.gov (United States)

    Bahtiyari, M. İ.

    2011-02-01

    A new method for the modification of the properties of polyamide fabric, based on exposure to the output from a CO 2 laser, has been investigated. It was found that, after laser modification of polyamide fabric, the dyeability of fabric was increased significantly, while the bursting strength was decreased. The reasons for this drastic increase in dyeability of polyamide fabrics have been analyzed with the help of FTIR and iodine sorption methods, revealing a relationship with a decrease in the crystallinity of the polyamide. It was observed that, as the laser modification of the fabric was carried out with low intensity, the concentration of free amino groups, which are necessary during dyeing with acid and reactive dyes, increased.

  17. Amino acid analysis in biological fluids by GC-MS

    OpenAIRE

    Kaspar, Hannelore

    2009-01-01

    Amino acids are intermediates in cellular metabolism and their quantitative analysis plays an important role in disease diagnostics. A gas chromatography-mass spectrometry (GC-MS) based method was developed for the quantitative analysis of free amino acids as their propyl chloroformate derivatives in biological fluids. Derivatization with propyl chloroformate could be carried out directly in the biological samples without prior protein precipitation or solid-phase extraction of the amino acid...

  18. 非淀粉多糖酶对玉米加工副产品氨基酸及养分真代谢率的影响%Non-Starch Polysaccharide-Degrading Enzymes: Effects on True Amino Acid and Nutrient Metabolic Rates of Corn By-Products

    Institute of Scientific and Technical Information of China (English)

    林谦; 王照群; 蒋桂韬; 王向荣; 张旭; 张建华; 戴求仲

    2013-01-01

    To study the effects of non-starch polysaccharide-degrading enzymes on true amino acid and nutrient metabolic rates of corn by-products,a complete randomized design and three metabolic test periods had been taken,and 56 healthy adult yellow-feathered roosters with an average body weight of (2.5 ± 0.2) kg were randomly divided into 7 groups with 8 replicates in each group and 1 rooster in each replicate.The roosters were force-fed with a single raw material and the material with non-starch polysaccharide-degrading enzymes to determine the true amino acid metabolic rates of corn and its by-products before and after the enzyme addition.Results showed that before the enzyme addition,the average true amino acid metabolic rate of corn was the highest,and the lowest one was germ (no spray,from Jining).After the enzyme was added,the true amino acid metabolic rates of corn by-products were between 70.77% to 99.29%,and the enzyme increased the true amino acid metabolic rates of corn by-products by 0.96% to 3.52%.The true metabolic rates of many amino acids in corn and corn gluten meal [crude protein (CP) 50% and CP 55%] were significantly increased by the supplementation of the enzyme (P < 0.05).And the effective nutrient improvement values (ENIV) of true available amino acid contents of corn by-products were in the range of 0.03 to 1.87 g/kg,the highest was corn gluten meal (CP 55%),and the lowest one was corn fiber feed.The supplementation of the enzyme can improve the metabolic rates of true CP,dry matter (DM) and ether extract (EE) of varieties of corn by-products (P > 0.05),and for some by-products it could significantly increase the true metabolic rates of DM and CP (P < 0.05).The enzyme could also significantly enhance the true crude fiber (CF) metabolic rate of all corn by-products (P < 0.05).Generally speaking,complex non-starch polysaccharide-degrading enzymes can improve the true amino acid and nutrient metabolic rates of corn and its by

  19. 昆虫抗药性机理:行为和生理改变及解毒代谢增强%Behavioral change, physiological modification, and metabolic detoxification: mechanisms of insecticide resistance

    Institute of Scientific and Technical Information of China (English)

    刘喃喃; 朱芳; 徐强; Julia W.PRIDGEON; 高希武

    2006-01-01

    Insecticide resistance is "the development of an ability in a strain of some organisms to tolerate doses of a toxicant which would prove lethal to a majority of individuals in a normal population of the same species".Mechanisms of resistance, such as behavioral change, physiological modification or metabolic detoxification, decrease the effective dose available at the target site. Behavioral resistance is defined as any behavior that reduces an insect's exposure to toxic compounds or that allows an insect to survive in an environment that is harmful and/or fatal to the majority of insects. Physiological modification mechanisms permit insects to survive lethal doses of a toxicant through decreased penetration of insecticides, increased sequestration/storage of insecticides, and accelerated excretion of insecticides. Metabolic detoxification is conferred by cytochrome P450 monooxygenases (cytochrome P450s),hydrolases, and glutathione transferases (GSTs). Cytochrome P450s constitute the largest gene superfamily and are critical for the detoxification and/or activation of xenobiotics and the metabolism of endogenous compounds. Increased P450-mediated detoxification has been found in many insect species, resulting in enhanced insecticide resistance.Glutathione transferases (GSTs) are soluble dimeric proteins involved in the metabolism, detoxification, and excretion of a large number of endogenous and exogenous compounds. Elevated GST activities have been implicated in resistance in many insect species. Hydrolases or esterases, a group of heterogeneous enzymes, have been identified as the active agents promoting hydrolase-mediated resistance that protect insects by either binding and sequestering insecticides through overproduction of proteins, or enhancing the metabolism of insecticides through increased enzyme activities.%杀虫剂抗性是指"生物的一个品系发展了对该生物正常种群中大多数个体具有致死作用剂量的杀虫药剂的能力".行

  20. The advance on modification of polyhydroxyalkanoates synthase and construction of metabolic pathways%聚羟基脂肪酸酯合成酶的改造和代谢途径构建的研究进展

    Institute of Scientific and Technical Information of China (English)

    李浩; 黄媛媛; 李曼; 宋水山

    2013-01-01

    Polyhydroxyalkanoates (PHA) are biopolyesters,which are accumulated intracellularly in granule as carbon and energy storage materials by many microorganisms under unbalanced conditions.PHA has drawn much attention due to its good material properties,such as biodegradability,biocompatibility and the potential substitutes of chemical plastic.However,PHA composed of shortchain-length or single hydroxyearboxylie acid monomer possesses some undesired material properties,it is necessary to synthesize PHA with multiple monomers in order to meet the practical requirements.The specificity of PHA synthetase and the metabolic pathway of PHA influence the composition of PHA,consequently influence the material and physicochemical properties of PHA.In this paper,the recent advances in the development of the modification to the PHA synthases and the construction of metabolic pathways for PHA were reviewed.%聚羟基脂肪酸酯(Polyhydroxyalkanoates,PHA)是许多细菌在非平衡生长条件下在胞内积累的以颗粒状态存在的碳源和能源储藏物质.PHA因其具有生物可降解性、生物相容性等许多良好的材料性质、可以作为化学合成塑料未来的替代品而引起广泛关注.但由短链脂肪酸或单一脂肪酸单体合成的PHA的材料性质具有局限性,需要利用多种单体合成满足实际需求的PHA材料.PHA合成酶的底物特异性和PHA合成代谢途径决定着PHA的单体组成情况,进而影响着PHA的理化特性和材料性能.因此需要对PHA合成酶进行改造,扩展其对底物的特异性.另一方面需要构建新的PHA合成代谢途径,能合成出一些不常见的且性能优良的PHA材料.综述了近些年对PHA合成酶改造的研究及PHA代谢途径构建的研究进展.

  1. Amino Acid Prodrugs: An Approach to Improve the Absorption of HIV-1 Protease Inhibitor, Lopinavir

    Directory of Open Access Journals (Sweden)

    Mitesh Patel

    2014-04-01

    Full Text Available Poor systemic concentrations of lopinavir (LPV following oral administration occur due to high cellular efflux by P-glycoprotein (P-gp and multidrug resistance-associated proteins (MRPs and extensive metabolism by CYP3A4 enzymes. In this study, amino acid prodrugs of LPV were designed and investigated for their potential to circumvent efflux processes and first pass effects. Three amino acid prodrugs were synthesized by conjugating isoleucine, tryptophan and methionine to LPV. Prodrug formation was confirmed by the LCMS/MS and NMR technique. Interaction of LPV prodrugs with efflux proteins were carried out in P-gp (MDCK-MDR1 and MRP2 (MDCK-MRP2 transfected cells. Aqueous solubility studies demonstrated that prodrugs generate higher solubility relative to LPV. Prodrugs displayed higher stability under acidic conditions and degraded significantly with rise in pH. Uptake and transport data suggested that prodrugs carry significantly lower affinity towards P-gp and MRP2 relative to LPV. Moreover, prodrugs exhibited higher liver microsomal stability relative to LPV. Hence, amino acid prodrug modification might be a viable approach for enhancing LPV absorption across intestinal epithelial and brain endothelial cells which expresses high levels of P-gp and MRP2.

  2. Perioperative period: immunological modifications.

    Science.gov (United States)

    Cardinale, F; Chinellato, I; Caimmi, S; Peroni, D G; Franceschini, F; Miraglia Del Giudice, M; Bernardini, R

    2011-01-01

    Surgical stress induces complex modifications in the hemodynamic, metabolic, neuro-hormonal and immune response of the individual. The magnitude of these alterations depends on preoperative events leading to surgery, the severity of surgical trauma, and also on post-operative/post-traumatic complications (multiple hit hypothesis). As in other conditions of tissue damage, surgery trauma is followed by an immune-inflammatory response, initiated at the site of injury by the innate immune system, followed by a compensatory anti-inflammatory (or immunosuppressive) response (CARS), involving mainly cells of the adaptive immune system, which predispose the host to septic complications. The up-regulated inflammatory response, together with a profound impairment of macrophage and cell-mediated immunity, appear to be the cause for patients' increased susceptibility in developing subsequent sepsis after major surgery. PMID:22014920

  3. DETERMINATION OF REGIMES FOR DIPHTHERIA EXOTOXIN MODIFICATION BY CHEMICAL AND PHYSICOCHEMICAL METHODS

    OpenAIRE

    Antusheva T.I.; Pluhator T.M.; Ryabovol O.V.; Sklyar N.I.,; Ryzhkova T.A.,; Kalinichenko S.V; Babych E.M.; Panova C.V.

    2011-01-01

    The possibility of diphtheria toxoid obtaining using chemical (amino sugars, organic acids) and physicochemical (amino sugars, organic acids, ultrasound, temperature) factors was studied. It was established that modifiers (including formaldehyde) volume content decreasing didn’t have significant influence on diphtheria toxin derived modifications specific activity. It was experimentally determined that diphtheria toxin modifications obtained by the instrumentality of modifier number 1 with or...

  4. Metabolic syndrome and migraine

    Directory of Open Access Journals (Sweden)

    Amit eSachdev

    2012-11-01

    Full Text Available Migraine and metabolic syndrome are highly prevaleirnt and costly conditions.The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogensis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise.

  5. Epigenetic Modifications and Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Renu A. Kowluru

    2013-01-01

    Full Text Available Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2 and matrix metalloproteinase-9 (MMP-9 are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1, and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.

  6. Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk.

    Science.gov (United States)

    Huber, Wolfgang W; Parzefall, Wolfram

    2005-01-01

    Enzymes of xenobiotic metabolism are involved in the activation and detoxification of carcinogens and can play a pivotal role in the susceptibility of individuals toward chemically induced cancer. Differences in such susceptibility are often related to genetically predetermined enzyme polymorphisms but may also be caused by enzyme induction or inhibition through environmental factors or in the frame of chemopreventive intervention. In this context, coffee consumption, as an important lifestyle factor, has been under thorough investigation. Whereas the data on a potential procarcinogenic effect in some organs remained inconclusive, epidemiology has clearly revealed coffee drinkers to be at a lower risk of developing cancers of the colon and the liver and possibly of several other organs. The underlying mechanisms of such chemoprotection, modifications of xenobiotic metabolism in particular, were further investigated in rodent and in vitro models, as a result of which several individual chemoprotectants out of the >1000 constituents of coffee were identified as well as some strongly metabolized individual carcinogens against which they specifically protected. This chapter discusses the chemoprotective effects of several coffee components and whole coffee in association with modifications of the usually protective glutathione-S-transferase (GST) and the more ambivalent N-acetyltransferase (NAT). A key role is played by kahweol and cafestol (K/C), two diterpenic constituents of the unfiltered beverage that were found to reduce mutagenesis/tumorigenesis by strongly metabolized compounds, such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, 7,12-dimethylbenz[a]anthracene, and aflatoxin B(1), and to cause various modifications of xenobiotic metabolism that were overwhelmingly beneficial, including induction of GST and inhibition of NAT. Other coffee components such as polyphenols and K/C-free coffee are also capable of increasing GST and partially of inhibiting NAT

  7. Metabolic responses of Saccharomyces cerevisiae to valine and ammonium pulses during four-stage continuous wine fermentations.

    Science.gov (United States)

    Clement, T; Perez, M; Mouret, J R; Sanchez, I; Sablayrolles, J M; Camarasa, C

    2013-04-01

    Nitrogen supplementation, which is widely used in winemaking to improve fermentation kinetics, also affects the products of fermentation, including volatile compounds. However, the mechanisms underlying the metabolic response of yeast to nitrogen additions remain unclear. We studied the consequences for Saccharomyces cerevisiae metabolism of valine and ammonium pulses during the stationary phase of four-stage continuous fermentation (FSCF). This culture technique provides cells at steady state similar to that of the stationary phase of batch wine fermentation. Thus, the FSCF device is an appropriate and reliable tool for individual analysis of the metabolic rerouting associated with nutrient additions, in isolation from the continuous evolution of the environment in batch processes. Nitrogen additions, irrespective of the nitrogen-containing compound added, substantially modified the formation of fermentation metabolites, including glycerol, succinate, isoamyl alcohol, propanol, and ethyl esters. This flux redistribution, fulfilling the requirements for precursors of amino acids, was consistent with increased protein synthesis resulting from increased nitrogen availability. Valine pulses, less efficient than ammonium addition in increasing the fermentation rate, were followed by a massive conversion of this amino acid in isobutanol and isobutyl acetate through the Ehrlich pathway. However, additional routes were involved in valine assimilation when added in stationary phase. Overall, we found that particular metabolic changes may be triggered according to the nature of the amino acid supplied, in addition to the common response. Both these shared and specific modifications should be considered when designing strategies to modulate the production of volatile compounds, a current challenge for winemakers.

  8. 低浓度DMSO对SH-SY5Y细胞存活率和氨基酸代谢的影响%Eff ect of Low Level of DMSO on Cell Survival Rate and Amino Acid Metabolism in SH-SY5Y Cells

    Institute of Scientific and Technical Information of China (English)

    李双; 王小琴; 郭春燕; 邹玉安

    2015-01-01

    Objective:To estimate the effect of dimethyl sulfoxide(DMSO) on livability and amino acid metabolism of SH-SY5Y cells.Methods:SH-SY5Y cells were divided into normal group and DMSO group. The DMSO group was exposed to 0.0125% DMSO in different time(24,48 h) to investigate amino acid transform which was associated with cell damage. SH-SY5Y cell livability was determined by MTT and amino acids content was determined by high performance liquid chromatography.Results:Compared with the normal group,7 amino acids(glutamic acid,glutamine,glycine,proline,phenylalanine,isoleucine,leucine) decreased significantly after treated with DMSO for 24 h(P<0.05),and 12 amino acids(glutamic acid, glutamine,glycine,proline,phenylalanine,isoleucine,leucine,serine,histidine,lysine, alanine,tryptophan) decreased significantly after treated with DMSO for 48 h(P<0.01). But there was no significant transform in cell vitality and morphological specificity.Conclusions:Although there was no obvious change in cell vitality and morphological specificity,but amino acid concentrations had significant transform. This findings imply that abnormal amino acid metabolism may be a potential early and causal feature of cell damage.%目的:研究二甲基亚砜(dimethyl sulfoxide,DMSO)对SH-SY5Y细胞存活率和氨基酸代谢的影响。方法:将细胞分为正常组和DMSO组。0.0125%浓度的DMSO作用SH-SY5Y细胞不同时间(24、48 h)后,利用MTT法测定细胞存活率;高效液相色谱法测定细胞中氨基酸的含量。结果:与正常组相比,在0.0125% DMSO作用下,细胞活力和形态差异无显著性,但细胞内氨基酸含量变化差异有显著性(P<0.05)。其中作用24 h,细胞中有7种氨基酸:谷氨酸(glutamic acid,Glu)、谷氨酰胺(glutamine,Gln)、甘氨酸(glycine,Gly)、脯氨酸(proline, Pro)、苯丙氨酸(phenylalanine,Phe)、异亮氨酸(isoleucine,Ile)、亮氨酸(leucine,Leu

  9. Amino acid racemisation dating

    Energy Technology Data Exchange (ETDEWEB)

    Murray-Wallace, C.V. [University of Wollongong, Wollongong, NSW (Australia). School of Geosciences

    1999-11-01

    The potential of the time-dependent amino acid racemisation reaction as a method of age assessment was first reported by Hare and Abelson (1968). They noted that in specimens of the bivalve mollusc Mercenaria sp., greater concentrations of amino acids in the D-configuration with increasing fossil age. Hare and Abelson (1968) also reported negligible racemisation in a modern specimen of Mecanaria sp. On this basis they suggested that the extent of amino acid racemisation (epimerisation in the case of isoleucine) may be used to assess the age of materials within and beyond the range of radiocarbon dating. For the past thirty years amino acid racemisation has been extensively applied in Quaternary research as a method of relative and numeric dating, and a particularly large literature has emerged on the subject 12 refs.

  10. Evolutionary systems biology of amino acid biosynthetic cost in yeast.

    Directory of Open Access Journals (Sweden)

    Michael D Barton

    Full Text Available Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental

  11. Amino acid uptake in rust fungi.

    Science.gov (United States)

    Struck, Christine

    2015-01-01

    The plant pathogenic rust fungi colonize leaf tissue and feed off their host plants without killing them. Certain economically important species of different genera such as Melampsora, Phakopsora, Puccinia, or Uromyces are extensively studied for resolving the mechanisms of the obligate biotrophy. As obligate parasites rust fungi only can complete their life cycle on living hosts where they grow through the leaf tissue by developing an extended network of intercellular hyphae from which intracellular haustoria are differentiated. Haustoria are involved in key functions of the obligate biotrophic lifestyle: suppressing host defense responses and acquiring nutrients. This review provides a survey of rust fungi nitrogen nutrition with special emphasis on amino acid uptake. A variety of sequences of amino acid transporter genes of rust fungi have been published; however, transport activity of only three in planta highly up-regulated amino acid permeases have been characterized. Functional and immunohistochemical investigations have shown the specificity and localization of these transporters. Sequence data of various genome projects allowed identification of numerous rust amino acid transporter genes. An in silico analysis reveals that these genes can be classified into different transporter families. In addition, genetic and molecular data of amino acid transporters have provided new insights in the corresponding metabolic pathways.

  12. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

    International Nuclear Information System (INIS)

    Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis. The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis

  13. Microbes Promote Amino Acid Harvest to Rescue Undernutrition in Drosophila

    Directory of Open Access Journals (Sweden)

    Ryuichi Yamada

    2015-02-01

    Full Text Available Microbes play an important role in the pathogenesis of nutritional disorders such as protein-specific malnutrition. However, the precise contribution of microbes to host energy balance during undernutrition is unclear. Here, we show that Issatchenkia orientalis, a fungal microbe isolated from field-caught Drosophila melanogaster, promotes amino acid harvest to rescue the lifespan of undernourished flies. Using radioisotope-labeled dietary components (amino acids, nucleotides, and sucrose to quantify nutrient transfer from food to microbe to fly, we demonstrate that I. orientalis extracts amino acids directly from nutrient-poor diets and increases protein flux to the fly. This microbial association restores body mass, protein, glycerol, and ATP levels and phenocopies the metabolic profile of adequately fed flies. Our study uncovers amino acid harvest as a fundamental mechanism linking microbial and host metabolism, and highlights Drosophila as a platform for quantitative studies of host-microbe relationships.

  14. Posttranslational Modifications of Ribosomal Proteins in Escherichia coli.

    Science.gov (United States)

    Nesterchuk, M V; Sergiev, P V; Dontsova, O A

    2011-04-01

    А number of ribosomal proteins inEscherichia coliundergo posttranslational modifications. Six ribosomal proteins are methylated (S11, L3, L11, L7/L12, L16, and L33), three proteins are acetylated (S5, S18, and L7), and protein S12 is methylthiolated. Extra amino acid residues are added to protein S6. С-terminal amino acid residues are partially removed from protein L31. The functional significance of these modifications has remained unclear. These modifications are not vital to the cells, and it is likely that they have regulatory functions. This paper reviews all the known posttranslational modifications of ribosomal proteins inEscherichia coli. Certain enzymes responsible for the modifications and mechanisms of enzymatic reactions are also discussed.

  15. Readers of histone modifications

    Institute of Scientific and Technical Information of China (English)

    Miyong Yun; Jun Wu; Jerry L Workman; Bing Li

    2011-01-01

    Histone modifications not only play important roles in regulating chromatin structure and nuclear processes but also can be passed to daughter cells as epigenetic marks.Accumulating evidence suggests that the key function of histone modifications is to signal for recruitment or activity of downstream effectors. Here, we discuss the latest discovery of histone-modification readers and how the modification language is interpreted.

  16. Economic aspects of amino acids production.

    Science.gov (United States)

    Mueller, Udo; Huebner, Susanna

    2003-01-01

    Amino acids represent basic elements of proteins, which as a main source of nutrition themselves serve as a major reserve for maintaining essential functions of humans as well as animals. Taking the recent state of scientific knowledge into account, the industrial sector of amino acids is a priori "suitable" to a specific kind of an ecologically sound way of production, which is based on biotechnology. The following article may point out characteristics of this particular industrial sector and illustrates the applicability of the latest economic methods, founded on development of the discipline of bionics in order to describe economic aspects of amino acids markets. The several biochemical and technological fields of application of amino acids lead to specific market structures in high developed and permanently evolving systems. The Harvard tradition of industrial economics explains how market structures mould the behaviour of the participants and influences market results beyond that. A global increase in intensity of competition confirms the notion that the supply-side is characterised by asymmetric information in contrast to Kantzenbachs concept of "narrow oligopoly" with symmetrical shared knowledge about market information. Departing from this point, certain strategies of companies in this market form shall be derived. The importance of Research and Development increases rapidly and leads to innovative manufacturing methods which replace more polluting manufacturing processes like acid hydrolysis. In addition to these modifications within the production processes the article deals furthermore with the pricing based on product life cycle concept and introduces specific applications of tools like activity based costing and target costing to the field of amino acid production. The authors come to the conclusion that based on a good transferability of latest findings in bionics and ecological compatibility competitors in amino acids manufacturing are well advised

  17. Economic aspects of amino acids production.

    Science.gov (United States)

    Mueller, Udo; Huebner, Susanna

    2003-01-01

    Amino acids represent basic elements of proteins, which as a main source of nutrition themselves serve as a major reserve for maintaining essential functions of humans as well as animals. Taking the recent state of scientific knowledge into account, the industrial sector of amino acids is a priori "suitable" to a specific kind of an ecologically sound way of production, which is based on biotechnology. The following article may point out characteristics of this particular industrial sector and illustrates the applicability of the latest economic methods, founded on development of the discipline of bionics in order to describe economic aspects of amino acids markets. The several biochemical and technological fields of application of amino acids lead to specific market structures in high developed and permanently evolving systems. The Harvard tradition of industrial economics explains how market structures mould the behaviour of the participants and influences market results beyond that. A global increase in intensity of competition confirms the notion that the supply-side is characterised by asymmetric information in contrast to Kantzenbachs concept of "narrow oligopoly" with symmetrical shared knowledge about market information. Departing from this point, certain strategies of companies in this market form shall be derived. The importance of Research and Development increases rapidly and leads to innovative manufacturing methods which replace more polluting manufacturing processes like acid hydrolysis. In addition to these modifications within the production processes the article deals furthermore with the pricing based on product life cycle concept and introduces specific applications of tools like activity based costing and target costing to the field of amino acid production. The authors come to the conclusion that based on a good transferability of latest findings in bionics and ecological compatibility competitors in amino acids manufacturing are well advised

  18. Amino acids in the cultivation of mammalian cells.

    Science.gov (United States)

    Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

    2016-05-01

    Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

  19. 晶体氨基酸替代鱼粉蛋白对半滑舌鳎稚鱼消化酶和代谢酶活力的影响%EFFECTS OF FISH MEAL REPLACEMENT WITH CRYSTALLINE AMINO ACID ON DIGESTIVE AND METABOLIC ENZYMES OF TONGUE SOLE (CYNOGLOSSUS SEMILAEVIS GÜNTHER, 1873) LARVAE

    Institute of Scientific and Technical Information of China (English)

    张珊; 艾庆辉; 麦康森; 徐玮; 韩冰

    2014-01-01

    The study was conducted to investigate the effects of replacement of fish meal protein by crystalline amino acids on digestive enzymes and metabolism enzymes in tongue sole larvae. Five isoproteic and isolipidic diets were formulated to replace 0%, 25%, 50%, 75%, 100% fish meal (0% CAA, 25% CAA, 50% CAA, 75% CAA and 100%CAA) respectively. At the replacement level of 25%, another diet was formulated with amino acids coated with tri-palmitin (C-25%CAA). Each micro diet was randomly fed to triplicate groups of fish, and each group had 150 fish. The results showed that the activities of trypsin significantly decreased with increasing dietary crystalline amino acids, but there were no significant differences between C-25%CAA and 0%CAA (P>0.05). The ratio of Trypsin(I) to Trypsin(P) significantly decreased with increasing dietary crystalline amino acids, and 0%CAA was significantly higher than 75%CAA and 100%CAA. The activities of amylase significantly increased with increasing dietary crystalline amino acids. The activities of leucine-amino peptidase and alkaline-phosphatase in intestine and purified brush border membrane of intestine significantly decreased with increasing dietary crystalline amino acids, but no significant differences were ob-served between C-25% CAA and 0% CAA (P>0.05). Glutamic-pyruvic transaminase and Glutamic-oxalacetic transa-minease significantly increased with increasing dietary crystalline amino acids. In conclusion, crystalline amino acids in the micro diet significantly influenced the digestive and metabolic enzymes of tongue sole larvae. In the replacement level of 25%, Comparing with 25% CAA group crystalline amino acids coated with tripalmitin (C-25% CAA) could promote the development of digestion system in tongue sole larvae.%为研究人工微颗粒饲料中晶体氨基酸替代鱼粉蛋白对半滑舌鳎(Cynoglossus semilaevis Günther)稚鱼消化酶和代谢酶活力的影响,以晶体氨基酸混合物分别替代0%、25%、50%、75

  20. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  1. Uptake of Branched-Chain Amino Acids by Streptococcus thermophilus

    OpenAIRE

    Akpemado, K. M.; Bracquart, P. A.

    1983-01-01

    The transport of branched-chain amino acids in Streptococcus thermophilus was energy dependent. The metabolic inhibitors of glycolysis and ATPase enzymes were active, but the proton-conducting uncouplers were not. Transport was optimal at temperatures of between 30 and 45°C and at pH 7.0 for the three amino acids leucine, valine, and isoleucine; a second peak existed at pH 5.0 with valine and isoleucine. By competition and kinetics studies, the branched-chain amino acids were found to share a...

  2. High-level production of C-11-carboxyl-labeled amino acids

    International Nuclear Information System (INIS)

    Carbon-11-labeled amino acids have significant potential as agents for positron tomographic functional imaging. We have developed a rapid, high-temperature, high-pressure modification of the Buecherer--Strecker amino acid synthesis and found it to be quite general for the production of C-11-carboxyl-labeled neutral amino acids. Production of C-11-carboxyl-labeled DL-tryptophan requires certain modifications in the procedure. Twelve different amino acids have been produced to date by this technique. Synthesis and chromatographic purification require approximately 40 min, and C-11-carboxyl-labeled amino acids have been produced in yields of up to 425 mCi. Two C-11-carboxyl-labeled amino acids are being investigated clinically for tumor scanning and two others for pancreatic imaging. Over 120 batches of the various agents have been produced for clinical use over a three-year period

  3. Azetidinic amino acids

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Bunch, Lennart; Chopin, Nathalie;

    2005-01-01

    A set of ten azetidinic amino acids, that can be envisioned as C-4 alkyl substituted analogues of trans-2-carboxyazetidine-3-acetic acid (t-CAA) and/or conformationally constrained analogues of (R)- or (S)-glutamic acid (Glu) have been synthesized in a diastereo- and enantiomerically pure form fr...

  4. Determining important regulatory relations of amino acids from dynamic network analysis of plasma amino acids.

    Science.gov (United States)

    Shikata, Nahoko; Maki, Yukihiro; Nakatsui, Masahiko; Mori, Masato; Noguchi, Yasushi; Yoshida, Shintaro; Takahashi, Michio; Kondo, Nobuo; Okamoto, Masahiro

    2010-01-01

    The changes in the concentrations of plasma amino acids do not always follow the flow-based metabolic pathway network. We have previously shown that there is a control-based network structure among plasma amino acids besides the metabolic pathway map. Based on this network structure, in this study, we performed dynamic analysis using time-course data of the plasma samples of rats fed single essential amino acid deficient diet. Using S-system model (conceptual mathematical model represented by power-law formalism), we inferred the dynamic network structure which reproduces the actual time-courses within the error allowance of 13.17%. By performing sensitivity analysis, three of the most dominant relations in this network were selected; the control paths from leucine to valine, from methionine to threonine, and from leucine to isoleucine. This result is in good agreement with the biological knowledge regarding branched-chain amino acids, and suggests the biological importance of the effect from methionine to threonine.

  5. Bioactivation of the heterocyclic aromatic amine 2-amino-3-methyl-9H-pyrido [2,3-b]indole (MeA alpha C) in recombinant test systems expressing human xenobiotic-metabolizing enzymes

    DEFF Research Database (Denmark)

    Glatt, H.; Pabel, U.; Meinl, W.;

    2004-01-01

    co-expressing cytochrome (CYP) 1A2 and sulphotransferase (SULT) 1A1 even at a concentration of 30 nM, but was inactive in cells co-expressing CYP1A2 and N-acetyltransferase (NAT) 1 or 2. MeAalphaC, tested in the presence of rat liver post-mitochondrial fraction, showed strongly enhanced mutagenicity......2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and some metabolites were investigated for mutagenicity in mammalian cell lines and bacterial strains engineered for the expression of human enzymes. MeAalphaC induced gene mutations (studied at the hprt locus) in Chinese hamster V79-derived cells...... in a Salmonella typhimurium strain expressing human SULT1A1 compared with the control (recipient) strain TA1538/1,8-DNP (deficient in endogenous acetyltransferase). Mutagenicity was also enhanced, although to a lesser extent, when NAT2 was expressed in the latter strain. The metabolite, 2-hydroxylamino-3-methyl-9...

  6. Laboratory Course on "Streptomyces" Genetics and Secondary Metabolism

    Science.gov (United States)

    Siitonen, Vilja; Räty, Kaj; Metsä-Ketelä, Mikko

    2016-01-01

    The "'Streptomyces' genetics and secondary metabolism" laboratory course gives an introduction to the versatile soil dwelling Gram-positive bacteria "Streptomyces" and their secondary metabolism. The course combines genetic modification of "Streptomyces"; growing of the strain and protoplast preparation, plasmid…

  7. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  8. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  9. Dammar resin, a non-mutagen, induces [corrected] oxidative stress and metabolic enzymes in the liver of gpt delta transgenic mouse which is different from a mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline.

    Science.gov (United States)

    Xie, Xiao-Li; Wei, Min; Kakehashi, Anna; Yamano, Shotaro; Okabe, Kyoko; Tajiri, Masaki; Wanibuchi, Hideki

    2012-10-01

    Dammar resin has long been used in foods as either a clouding or a glazing agent. In a recent study, 2% Dammar resin showed significant hepatocarcinogenicity in a rat 2-year bioassay. Therefore, for an accurate estimate of human risk, it is necessary to understand whether Dammar resin induces liver genotoxicity and the underlying mechanisms of its hepatocarcinogenicity. Modifying effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a typical genotoxic carcinogen produced during cooking of protein-rich foods, was also studied in the present study. Exposure of gpt delta mice to Dammar resin at a dose of 2% for 12 weeks did not induce any obvious mutagenicity in the liver. However, the index of cell proliferation, the level of 8-OHdG, and bax, bcl-2, p53, cyp1a2, cyp2e1, gpx1 and gstm2 gene expression were all significantly increased when compared with the control group. In the IQ treatment group, at a dose of 300ppm, mutagenicity was readily detected, the index of cell proliferation increased, and p53, cyp2e1 and gpx1 gene expression was down-regulated in the liver. Down-regulation of p53, P450s, and gpx1 in the livers of IQ treated mice are consistent with its genotoxic mechanism of carcinogenicity observed in a 675-day study. In contrast, our results using gpt delta mice suggest that Dammar resin is not genotoxic. Instead, the Dammar resin-induced hepatocarcinogenicity seen in our previous 2-year study with rats may have been mediated by non-genotoxic mechanisms, including increased P450 enzyme activity, increased oxidative stress, altered gene expression, and promotion of cell proliferation.

  10. Cerebral metabolic and circulatory effects of 1,1,1-trichloroethane, a neurotoxic industrial solvent. 2. Tissue concentrations of labile phosphates, glycolytic metabolites, citric acid cycle intermediates, amino acids, and cyclic nucleotides.

    Science.gov (United States)

    Folbergrová, J; Hougaard, K; Westerberg, E; Siesjö, B K

    1984-01-01

    In order to obtain information on the mechanisms of neurotoxicity of 1,1,1-trichloroethane, rats maintained artificially ventilated on N2O:O2 (70:30) were exposed to a concentration of 1,1,1-trichloroethane of 8000 ppm, 43.7 mg L-1, that induces moderate ataxia in awake, spontaneously breathing animals. After 5 and 60 min of exposure, as well as after a 60-min recovery period following 60 min of exposure, the brain was frozen in situ and cortical tissue was assayed for phosphocreatine (PCr), + ATP, ADP, AMP, glycogen, glucose, pyruvate, lactate, citric acid cycle intermediates, associated amino acids, and cyclic nucleotides; in addition, purine nucleotides, nucleosides, and bases were assayed by HPLC techniques. Exposure of animals to 1,1,1-trichloroethane failed to alter blood glucose, lactate, and pyruvate concentrations. However, the solvent induced highly significant increases in tissue lactate and pyruvate concentrations that were also reflected in cisternal CSF. Associated with these changes were increases in all citric acid cycle intermediates except succinate, an increase in alanine concentration, and a rise in the glutamate/aspartate ratio. After 5 min, a small decrease in glycogen concentration also occurred. All these changes were reversed when the exposure was terminated. No changes were observed in tissue concentrations of purine nucleotides, nucleosides, and bases except for a small reduction of ATP concentration after 60 min of exposure, still noticeable after 60 min of recovery. Apart from a small reduction in cAMP concentration after 5 min of exposure, cyclic nucleotide concentrations did not change.

  11. Surface Modification for Microreactor Fabrication

    Directory of Open Access Journals (Sweden)

    Wladyslaw Torbicz

    2006-04-01

    Full Text Available In this paper, methods of surface modification of different supports, i.e. glass andpolymeric beads for enzyme immobilisation are described. The developed method ofenzyme immobilisation is based on Schiff’s base formation between the amino groups onthe enzyme surface and the aldehyde groups on the chemically modified surface of thesupports. The surface of silicon modified by APTS and GOPS with immobilised enzymewas characterised by atomic force microscopy (AFM, time-of-flight secondary ion massspectroscopy (ToF-SIMS and infrared spectroscopy (FTIR. The supports withimmobilised enzyme (urease were also tested in combination with microreactors fabricatedin silicon and Perspex, operating in a flow-through system. For microreactors filled withurease immobilised on glass beads (Sigma and on polymeric beads (PAN, a very high andstable signal (pH change was obtained. The developed method of urease immobilisationcan be stated to be very effective.

  12. Functionalized 2′-amino-α-L-LNA

    DEFF Research Database (Denmark)

    Kumar, T. Santhosh; Madsen, Andreas Stahl; Østergaard, Michael;

    2009-01-01

    characterization, and molecular modeling of N2′-functionalized 2′-amino-α-L-LNA is described. Chemoselective N2′-functionalization of protected amino alcohol 1 followed by phosphitylation afforded a structurally varied set of target phosphoramidites, which were incorporated into oligodeoxyribonucleotides......′-functionalities such as 2′-N-acetyl-2′-amino-α-L-LNA (monomer V) had detrimental effects on thermal affinity toward DNA/RNA complements with decreases of as much as -16.5 °C per modification. Extensive thermal DNA selectivity, favorable entropic contributions upon duplex formation, hybridization......-induced bathochromic shifts of pyrene absorption maxima and increases in circular dichroism signal intensity, and molecular modeling studies suggest that pyrene-functionalized 2′-amino-α-L-LNA monomers W-Y having short linkers between the bicyclic skeleton and the pyrene moiety allow high-affinity hybridization...

  13. Age-related changes of muscle and plasma amino acids in healthy children.

    Science.gov (United States)

    Hammarqvist, Folke; Angsten, Gertrud; Meurling, Staffan; Andersson, Kerstin; Wernerman, Jan

    2010-07-01

    The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.

  14. Amino acid analysis.

    Science.gov (United States)

    Crabb, J W; West, K A; Dodson, W S; Hulmes, J D

    2001-05-01

    Amino acid analysis (AAA) is one of the best methods to quantify peptides and proteins. Two general approaches to quantitative AAA exist, namely, classical postcolumn derivatization following ion-exchange chromatography and precolumn derivatization followed by reversed-phase HPLC (RP-HPLC). Excellent instrumentation and several specific methodologies are available for both approaches, and both have advantages and disadvantages. This unit focuses on picomole-level AAA of peptides and proteins using the most popular precolumn-derivatization method, namely, phenylthiocarbamyl amino acid analysis (PTC-AAA). It is directed primarily toward those interested in establishing the technology with a modest budget. PTC derivatization and analysis conditions are described, and support and alternate protocols describe additional techniques necessary or useful for most any AAA method--e.g., sample preparation, hydrolysis, instrument calibration, data interpretation, and analysis of difficult or unusual residues such as cysteine, tryptophan, phosphoamino acids, and hydroxyproline. PMID:18429107

  15. Quantitative amino acid profiling and stable isotopically labeled amino acid tracer enrichment used for in vivo human systemic and tissue kinetics measurements

    DEFF Research Database (Denmark)

    Bornø, Andreas; van Hall, Gerrit

    2014-01-01

    . The present study describes a new sensitive liquid chromatography tandem mass-spectrometry method quantifying 20 amino acids and their tracer(s) ([ring-(13)C6]/D5Phenylalanine) in human plasma and skeletal muscle specimens. Before analysis amino acids were extracted and purified via deprotonization...... curve correlations for amino acids were on average; r(2)=0.998. Interday accuracy for amino acids determined in spiked plasma was on average 97.3% and the coefficient of variation (CV) was 2.6%. The ([ring-(13)C6]/D5Phenylalanine) enrichment CV's for machine reproducibility in muscle tissue fluid......An important area within clinical functional metabolomics is in vivo amino acid metabolism and protein turnover measurements for which accurate amino acid concentrations and stable isotopically labeled amino acid enrichments are mandatory not the least when tissue metabolomics is determined...

  16. Single amino acid supplementation in aminoacidopathies : a systematic review

    NARCIS (Netherlands)

    van Vliet, Danique; Derks, Terry G. J.; van Rijn, Margreet; de Groot, Martijn J.; MacDonald, Anita; Heiner-Fokkema, M. Rebecca; van Spronsen, Francjan J.

    2014-01-01

    Aminoacidopathies are a group of rare and diverse disorders, caused by the deficiency of an enzyme or transporter involved in amino acid metabolism. For most aminoacidopathies, dietary management is the mainstay of treatment. Such treatment includes severe natural protein restriction, combined with

  17. Glial metabolism of valine.

    Science.gov (United States)

    Murín, Radovan; Mohammadi, Ghasem; Leibfritz, Dieter; Hamprecht, Bernd

    2009-07-01

    The three essential amino acids, valine, leucine and isoleucine, constitute the group of branched-chain amino acids (BCAAs). BCAAs are rapidly taken up into the brain parenchyma, where they serve several distinct functions including that as fuel material in brain energy metabolism. As one function of astrocytes is considered the production of fuel molecules that support the energy metabolism of adjacent neural cells in brain. Astroglia-rich primary cultures (APC) were shown to rapidly dispose of the BCAAs, including valine, contained in the culture medium. While the metabolisms of leucine and isoleucine by APC have already been studied in detail, some aspects of valine metabolism remained to be determined. Therefore, in the present study an NMR analysis was performed to identify the (13)C-labelled metabolites that are generated by APC during catabolism of [U-(13)C]valine and that are subsequently released into the incubation medium. The results presented show that APC (1) are potently disposing of the valine contained in the incubation medium; (2) are capable of degrading valine to the tricarboxylic acid (TCA) cycle member succinyl-CoA; and (3) release into the extracellular milieu valine catabolites and compounds generated from them such as [U-(13)C]2-oxoisovalerate, [U-(13)C]3-hydroxyisobutyrate, [U-(13)C]2-methylmalonate, [U-(13)C]isobutyrate, and [U-(13)C]propionate as well as several TCA cycle-dependent metabolites including lactate.

  18. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  19. Modify or die? - RNA modification defects in metazoans

    Science.gov (United States)

    Sarin, L Peter; Leidel, Sebastian A

    2014-01-01

    Chemical RNA modifications are present in all kingdoms of life and many of these post-transcriptional modifications are conserved throughout evolution. However, most of the research has been performed on single cell organisms, whereas little is known about how RNA modifications contribute to the development of metazoans. In recent years, the identification of RNA modification genes in genome wide association studies (GWAS) has sparked new interest in previously neglected genes. In this review, we summarize recent findings that connect RNA modification defects and phenotypes in higher eukaryotes. Furthermore, we discuss the implications of aberrant tRNA modification in various human diseases including metabolic defects, mitochondrial dysfunctions, neurological disorders, and cancer. As the molecular mechanisms of these diseases are being elucidated, we will gain first insights into the functions of RNA modifications in higher eukaryotes and finally understand their roles during development. PMID:25692999

  20. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  1. Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development.

    Science.gov (United States)

    Wendisch, Volker F

    2014-12-01

    Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids. PMID:24922334

  2. Selective modification of phosphoribulokinase cysteines

    Energy Technology Data Exchange (ETDEWEB)

    Krieger, T.J.; Mende-Mueller, L.M.; Miziorko, H.M.

    1987-05-01

    The most reactive sulfhydryl in native phosphoribulokinase can be selectively alkylated with iodoacetate; complete loss of activity results. Composition and N-terminal analyses of the peptide bearing this -SH show that cys-16 is the modification site. In the presence of Mg and ATP, a nonessential -SH is modified; catalytic activity is unchanged. The peptide bearing this cysteine has been characterized by amino acid composition and N-terminal analyses (Phe-Phe-Asn-Pro-Val-Tyr-(Ile/Leu)...). Enzyme alkylated at this site is subject to reversible oxidative inactivation, showing that this cysteine is not involved in regulation of activity. A cysteine distinct from this nonessential residue is suggested by crosslinking studies to be close (5a) to cys-16. The site-directed inhibitor fluorosulfonylbenzoyladenosine (FSBA) inactivates enzyme by modifying cys-16. Carboxymethylation of enzyme after FSBA incorporation, followed by DTT treatment, unmasks the initial modification site and allows (/sup 14/C)-iodoacetate labeling. The tryptic peptide bearing this residue co-chromatographs with and is identical in composition to the cys-16 containing peptide.

  3. Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production

    Directory of Open Access Journals (Sweden)

    Yoon Byoung

    2009-01-01

    Full Text Available Abstract Background Deletion of large blocks of nonessential genes that are not needed for metabolic pathways of interest can reduce the production of unwanted by-products, increase genome stability, and streamline metabolism without physiological compromise. Researchers have recently constructed a reduced-genome Escherichia coli strain MDS42 that lacks 14.3% of its chromosome. Results Here we describe the reengineering of the MDS42 genome to increase the production of the essential amino acid L-threonine. To this end, we over-expressed a feedback-resistant threonine operon (thrA*BC, deleted the genes that encode threonine dehydrogenase (tdh and threonine transporters (tdcC and sstT, and introduced a mutant threonine exporter (rhtA23 in MDS42. The resulting strain, MDS-205, shows an ~83% increase in L-threonine production when cells are grown by flask fermentation, compared to a wild-type E. coli strain MG1655 engineered with the same threonine-specific modifications described above. And transcriptional analysis revealed the effect of the deletion of non-essential genes on the central metabolism and threonine pathways in MDS-205. Conclusion This result demonstrates that the elimination of genes unnecessary for cell growth can increase the productivity of an industrial strain, most likely by reducing the metabolic burden and improving the metabolic efficiency of cells.

  4. INTERRUPTION OF AMINO ACIDS MOLECULAR ASYMMETRY (D/L- ENANTIOMERS DURING NORMAL AGING AND NEURODEGENERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    A.V. Chervyakov

    2010-05-01

    Full Text Available Some facts about D-amino acids, their diffusion in human’s and animal’s organisms, metabolism, identification methods, involving in ageing and pathogenesis of some neurodegenerative diseases are show in this review. Also there is discussing the role of amino acid molecular asymmetry (D and L enantiomers ratio as a fundamental asymmetry of living matter.

  5. EFFECT OF TETRACYCLINES ON THE INTRACELLULAR AMINO ACIDS OF MOLDS.

    Science.gov (United States)

    FREEMAN, B A; CIRCO, R

    1963-07-01

    Freeman, Bob A. (University of Chicago, Chicago, Ill.) and Richard Circo. Effect of tetracyclines on the intracellular amino acids of molds. J. Bacteriol. 86:38-44. 1963.-The tetracycline antibiotics were shown to alter the amino acid metabolism of molds whose growth is not markedly affected. Eight molds were grown in the presence of these antiobiotics; four exhibited a general reduction in the concentration of the intracellular amino acids, except for glutamic acid and alanine. In most of these four cultures, the tetracyclines also caused the complete disappearance of arginine, lysine, proline, phenylalanine, and tyrosine from the intracellular amino acid pool. The significance of these observations and the usefulness of the method in the study of the mechanisms of antibiotic action are discussed. PMID:14051820

  6. Diastereoselective Ugi reaction for the synthesis of unnatural amino esters

    Directory of Open Access Journals (Sweden)

    Rafael Oliveira Rocha

    2012-06-01

    Full Text Available Multicomponent Reactions (MCR are useful reactions to obtain complex products by the simple mixture of 3 or more reactants. The classic Ugi reaction (4-UCR involves a mixture of an amine, aldehyde, isocyanide and a carboxylic acid, giving peptoides as products. Some modifications of this reaction have been reported, among which the use of amino acids and Lewis acids, such as titanium (IV chloride, to induce stereoselectivity in good ratio. In this work we demonstrate the efficiency of different Lewis acids in the modified Ugi reaction and good levels of diastereoselectivity and yields in the synthesis of unnatural secondary amino esters.

  7. Mechanisms controlling renal hemodynamics and electrolyte excretion during amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Woods, L.L.; Mizelle, H.L.; Montani, J.P.; Hall, J.E.

    1986-08-01

    Our purpose was to investigate the mechanisms by which increased plasma amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR). Since transport of amino acids and Na is linked in the proximal tubule, the authors hypothesized that increased amino acids might stimulate proximal tubular Na reabsorption (PR/sub Na/) and thus increase RBF and GFR by a macula densa feedback mechanism. A solution of four amino acids (Ala, Ser, Gly, Pro) was infused intravenously into anesthetized dogs with normal kidneys (NK) and with kidneys in which the tubuloglomerular feedback mechanism was blunted by lowering renal artery pressure (LPK) or blocked by making the kidneys nonfiltering (NFK). In NK, RBF and GFR increased by 35 +/- 4% and 30 +/- 7% after 90 min of amino acid infusion, while PR/sub Na/ (estimated from lithium clearance) and O2 consumption increased by 31 +/- 5% and 29 +/- 5% and distal Na delivery remained relatively constant. Autoregulation of RBF and GFR in response to step deceases in renal artery pressure was impaired during amino acids in NK. The hemodynamic responses to amino acids were abolished in LPK and NFK. Infusion of the nonmetabolized -aminoisobutyric acid into NK produced changes in renal hemodynamics that were similar to the responses observed with the four metabolizable amino acids. These data are consistent with the hypothesis that elevation of plasma amino acids increases RBF and GFR by a mechanism that requires an intact macula densa feedback. Metabolism of the amino acids does not appear to be necessary for these changes to occur.

  8. High hydrostatic pressure increases amino acid requirements in the piezo-hyperthermophilic archaeon Thermococcus barophilus.

    Science.gov (United States)

    Cario, Anaïs; Lormières, Florence; Xiang, Xiao; Oger, Philippe

    2015-11-01

    We have established a defined growth medium for the piezophilic hyperthermophilic archaeon Thermococcus barophilus, which allows growth yields of ca. 10(8) cells/ml under both atmospheric and high hydrostatic pressure. Our results demonstrate a major impact of hydrostatic pressure on amino acid metabolism, with increases from 3 amino acids required at atmospheric pressure to 17 at 40 MPa. We observe in T. barophilus and other Thermococcales a similar discrepancy between the presence/absence of amino acid synthesis pathways and amino acid requirements, which supports the existence of alternate, but yet unknown, amino acid synthesis pathways, and may explain the low number of essential amino acids observed in T. barophilus and other Thermococcales. T. barophilus displays a strong metabolic preference for organic polymers such as polypeptides and chitin, which may constitute a more readily available resource of carbon and energy in situ in deep-sea hydrothermal vents. We hypothesize that the low energy yields of fermentation of organic polymers, together with energetic constraints imposed by high hydrostatic pressure, may render de novo synthesis of amino acids ecologically unfavorable. Induction of this metabolic switch to amino acid recycling can explain the requirement for non-essential amino acids by Thermococcales for efficient growth in defined medium.

  9. Evaluation on the Apparent Metabolic Energy and Apparent Heal Amino Acid Digestibility of Broccoli LPC and Broccoli Residues for Broilers%西兰花叶蛋白和茎叶粉对肉仔鸡代谢能和回肠氨基酸表观消化率的影响

    Institute of Scientific and Technical Information of China (English)

    杨桂芹; 梁丽萍; 李建涛; 刘国华; 张姝; 郑爱娟

    2011-01-01

    通过2个试验测定了西兰花叶蛋白和茎叶粉在肉仔鸡中的氮校正表观代谢能和回肠氨基酸的表观消化率,为合理利用西兰花资源提供科学依据和数据参考.试验1选用体重相近的22日龄健康肉仔鸡144只,随机分成3个组,每组8个重复,公母各50%.其中1组饲喂基础日粮,另2组分别饲喂试验日粮(西兰花叶蛋白30%替代基础日粮,西兰花茎叶粉35%替代基础日粮).选用TiO2为外源指示剂进行代谢试验;试验2选用体重相近的26日龄健康肉仔鸡96只,随机分为2组,每组8个重复,公母各50%.选用TiO2为外源指示剂,采用回肠末端法进行代谢试验.结果表明:西兰花叶蛋白和茎叶粉在肉仔鸡中的表观代谢能分别为8.86MJ·kg-1和2.48 MJ·kg-1,氮校正表观代谢能分别为8.14 MJ·kg-1和1.86 MJ·kg-1;西兰花叶蛋白和茎叶粉在肉仔鸡中4种限制性氨基酸的回肠末端表观消化率分别为赖氨酸(48.11±4.28)%和(73.00±6.64)%,蛋氨酸(39.51±4.60)%和(79.18±3.91)%,苏氨酸(33.11±4.66)%和(59.38±6.25)%,胱氨酸(33.47±2.94)%和(65.82±4.46)%;存肉仔鸡中17种氨基酸的回肠末端表观消化率的平均值为(39.57±4.45)%和(71.75±4.85)%.可见,西兰花茎叶粉在肉仔鸡中的表观代谢能较低,西兰花叶蛋白在肉仔鸡中回肠末端氨基酸的消化率较低.%To assess the apparent metabolic energy and apparent ileal amino acid digestibility of broccoli leaf protein concentrate (LPC) and broccoli residues for broilers, two experiments were carried out. In experiment one,one hundred and forty-four 22-day-old broilers were allocated randomly into three treatments,each of them contained eight repetitions, male and female half and haft. Titanium dioxide was used as the exogenous indicator to carry out the metabolic test, One group was fed basic diet, other two groups were fed test diets in which the basic diet was replaced by 30% broccoli LPC and 35% broccoli residues respectively. In

  10. Alimentary proteins, amino acids and cholesterolemia.

    Science.gov (United States)

    Blachier, François; Lancha, Antonio H; Boutry, Claire; Tomé, Daniel

    2010-01-01

    Numerous data from both epidemiological and experimental origins indicate that some alimentary proteins and amino acids in supplements can modify the blood LDL cholesterol, HDL cholesterol and total cholesterol. After an initial approval of the health claim for soy protein consumption for the prevention of coronary heart disease, more recently it has been concluded from an overall analysis of literature that isolated soy protein with isoflavones only slightly decrease LDL and total cholesterol. Other plant extracts and also some proteins from animal origin have been reported to exert a lowering effect on blood cholesterol when compared with a reference protein (often casein). The underlying mechanisms are still little understood. Individual amino acids and mixture of amino acids have also been tested (mostly in animal studies) for their effects on cholesterol parameters and on cholesterol metabolism. Methionine, lysine, cystine, leucine, aspartate and glutamate have been tested individually and in combination in different models of either normo or hypercholesterolemic animals and found to be able to modify blood cholesterol and/or LDL cholesterol and/or HDL cholesterol. It is however not known if these results are relevant to human nutrition.

  11. Chemical modification of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens

    NARCIS (Netherlands)

    Wijnands, R.A.

    1984-01-01

    Chemical modification was used to examine the role of some amino acid residues in the binding of the substrates to the enzyme p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. Ionic strength dependent binding studies were used to investigate the role of the protein as a whole in the comple

  12. The ACE-inhibitory Activity in Vitro of Casein Hydrolysates Subjected to Enzymatic Modification in the Presence of Three Extrinsic Amino Acids%三种氨基酸添加下酶法修饰酪蛋白水解物的ACE抑制活性

    Institute of Scientific and Technical Information of China (English)

    汪敬科; 赵新淮

    2011-01-01

    采用碱性蛋白酶水解酪蛋白,制备水解度为12.4%、IC50为42.19μg/mL的酪蛋白水解物.在添加外源氨基酸的情况下对水解物进行类蛋白反应修饰,并响应面法研究氨基酸添加量、酶添加量、反应温度及3种氨基酸的影响.结果表明:氨基酸添加量、反应温度、氨基酸种类对修饰反应影响显著,而酶添加量的影响不大;分别添加苯丙氨酸、亮氨酸、缬氨酸制备3个酪蛋白水解物修饰产物,其IC50降低至21.03~25.13 μg/mL,表明添加外源氨基酸可提高修饰产物的体外ACE抑制活性,但添加不同氨基酸的影响不显著.%Casein hydrolysates that had a degree of hydrolysis of 12.4 % and ACE-inhibition with an IC50 value of 42.19 μg/mL were prepared from casein with a protease Alcalase, and then modified by plastein reaction with Alcalase in the presence of three extrinsic amino acids.The effects of the addition level of amino acids, the addition level of Alcalase, reaction temperature and the types of amino acids on the plastein reaction of casein hydrolysates were investigated with response surface methodology.The results indicated that the addition of amino acids, reaction temperature and the types of amino acid added had significant impact on the plastein reaction, while the addition of Alca lase gave little influence.Three modified casein hydrolysates were prepared with suitable conditions and in the presence of phenylalanine, leucine and valine, respectively.Their IC50 values were in range of 21.03 to 25.13 μg/mL,indicating that the ACE-inhibitory activity in vitro of the modified casein hydrolysates was improved significantly by adding amino acids while the types of amino acids were not important to the activity.

  13. Characterization of N,N-dimethyl amino acids by electrospray ionization-tandem mass spectrometry.

    Science.gov (United States)

    Naresh Chary, V; Sudarshana Reddy, B; Kumar, Ch Dinesh; Srinivas, R; Prabhakar, S

    2015-05-01

    Methylation is an essential metabolic process for a number of critical reactions in the body. Methyl groups are involved in the healthy function of the body life processes, by conducting methylation process involving specific enzymes. In these processes, various amino acids are methylated, and the occurrence of methylated amino acids in nature is diverse. Nowadays, mass-spectrometric-based identification of small molecules as biomarkers for diseases is a growing research. Although all dimethyl amino acids are metabolically important molecules, mass spectral data are available only for a few of them in the literature. In this study, we report synthesis and characterization of all dimethyl amino acids, by electrospray ionization-tandem mass spectrometry (MS/MS) experiments on protonated molecules. The MS/MS spectra of all the studied dimethyl amino acids showed preliminary loss of H2O + CO to form corresponding immonium ions. The other product ions in the spectra are highly characteristic of the methyl groups on the nitrogen and side chain of the amino acids. The amino acids, which are isomeric and isobaric with the studied dimethyl amino acids, gave distinctive MS/MS spectra. The study also included MS/MS analysis of immonium ions of dimethyl amino acids that provide information on side chain structure, and it is further tested to determine the N-terminal amino acid of the peptides.

  14. Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications

    Directory of Open Access Journals (Sweden)

    Asadollahi Mohammad A

    2010-12-01

    Full Text Available Abstract Background The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where selective pressure is applied to a partially genetically engineered strain to confer a desirable phenotype. The exact genetic modification or resulting genotype that leads to the improved phenotype is often not identified or understood to enable further metabolic engineering. Results In this work we performed whole genome high-throughput sequencing and annotation can be used to identify single nucleotide polymorphisms (SNPs between Saccharomyces cerevisiae strains S288c and CEN.PK113-7D. The yeast strain S288c was the first eukaryote sequenced, serving as the reference genome for the Saccharomyces Genome Database, while CEN.PK113-7D is a preferred laboratory strain for industrial biotechnology research. A total of 13,787 high-quality SNPs were detected between both strains (reference strain: S288c. Considering only metabolic genes (782 of 5,596 annotated genes, a total of 219 metabolism specific SNPs are distributed across 158 metabolic genes, with 85 of the SNPs being nonsynonymous (e.g., encoding amino acid modifications. Amongst metabolic SNPs detected, there was pathway enrichment in the galactose uptake pathway (GAL1, GAL10 and ergosterol biosynthetic pathway (ERG8, ERG9. Physiological characterization confirmed a strong deficiency in galactose uptake and metabolism in S288c compared to CEN.PK113-7D, and similarly, ergosterol content in CEN.PK113-7D was significantly higher in both glucose and galactose supplemented cultivations compared to S288c. Furthermore, DNA microarray profiling of S288c and CEN.PK113-7D in both glucose and galactose batch cultures did not provide a clear hypothesis for major phenotypes observed, suggesting that

  15. Chiral morphology of calcite through selective binding of amino acids

    Science.gov (United States)

    Orme, Christine

    2002-03-01

    Many living organisms contain biominerals and composites with finely tuned properties, reflecting a remarkable level of control over the nucleation, growth and shape of the constituent crystals. Peptides and proteins play an important role in achieving this control. Using in situ AFM we find that site-specific binding of amino acid residues to surface steps changes the step-edge free energies, giving rise to direction-specific binding energies unique to individual amino acid enantiomers and leading to chiral modifications that propagate from atomic length scales to macroscopic length scales. Molecular modeling studies support an energetic basis for the differences in binding. Our results emphasize that the mechanism under-lying crystal modification through organic molecules is best understood by considering both stereochemical recognition as well as the effects of binding on the interfacial energies of the growing crystal.

  16. Oxidative Modification of Cytochrome c by Tetrahydropapaveroline, an Isoquinoline-Derived Neurotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jung Hoon [Cheongju Univ., Cheongju (Korea, Republic of)

    2013-02-15

    Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

  17. Covalently functionalized graphene sheets with biocompatible natural amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Mallakpour, Shadpour, E-mail: mallak@cc.iut.ac.ir [Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Abdolmaleki, Amir, E-mail: abdolmaleki@cc.iut.ac.ir [Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of); Borandeh, Sedigheh [Organic Polymer Chemistry Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan, 84156-83111, Islamic Republic of Iran (Iran, Islamic Republic of)

    2014-07-01

    Graphene sheets were covalently functionalized with aromatic–aliphatic amino acids (phenylalanine and tyrosine) and aliphatic amino acids (alanine, isoleucine, leucine, methionine and valine) by simple and green procedure. For this aim, at first natural graphite was converted into graphene oxide (GO) through strong oxidation procedure; then, based on the surface-exposed epoxy and carboxylic acid groups in GO solid, its surface modification with naturally occurring amino acids, occurred easily throughout the corresponding nucleophilic substitution and condensation reactions. Amino acid functionalized graphene demonstrates stable dispersion in water and common organic solvents. Fourier transform infrared, Raman and X-ray photoelectron spectroscopies, X-ray diffraction, field emission scanning electron microscopy and transmission electron microscopy were used to investigate the nanostructures and properties of prepared materials. Each amino acid has different considerable effects on the structure and morphology of the pure graphite, from increasing the layer spacing to layer scrolling, based on their structures, functional groups and chain length. In addition, therogravimetric analysis was used for demonstrating a successful grafting of amino acid molecules to the surface of graphene.

  18. Environmental Modification: A Study

    Science.gov (United States)

    Grinnell, Richard M., Jr.; Kyte, Nancy S.

    1975-01-01

    This study shows that environmental modification is a surprisingly intricate technique. This may account for its relatively low use and also for its more frequent use by MSW than non-MSW caseworkers. The findings indicate the need for further research on environmental modification. (Author)

  19. Permit application modifications

    International Nuclear Information System (INIS)

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils

  20. Permit application modifications

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

  1. Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1.

    Science.gov (United States)

    Nässl, Anna-Maria; Rubio-Aliaga, Isabel; Fenselau, Henning; Marth, Mena Katharina; Kottra, Gabor; Daniel, Hannelore

    2011-07-01

    The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1(-/-) compared with Pept1(+/+) animals, suggesting that amino acid handling is altered. Plasma appearance rates of (15)N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism. PMID:21350187

  2. Lifestyle modifications for GDM.

    Science.gov (United States)

    Dhingra, Atul; Ahuja, Kamlesh

    2016-09-01

    Prevalence of gestational diabetes mellitus (GDM) is increasing worldwide more so in Southeast Asian countries like India and Pakistan. 1 GDM is associated with various adverse foetal and maternal effects. The management of GDM aims at reducing blood glucose to reduce maternal and foetal morbidity and mortality. Various studies have shown that lifestyle modifications are an important tool for reducing blood glucose levels in patients with GDM. Lifestyle modifications consist of dietary modifications and daily physical activity. Dietary modifications aim to achieve glycaemic control by providing adequate calories to the mother and foetus. Exercise is an obvious adjunct to dietary modifications for management of GDM. Therefore the purpose of this review is to summarize the benefits of lifestyle interventions in patients with GDM. PMID:27582149

  3. Microbial Products Trigger Amino Acid Exudation from Plant Roots1

    Science.gov (United States)

    Phillips, Donald A.; Fox, Tama C.; King, Maria D.; Bhuvaneswari, T.V.; Teuber, Larry R.

    2004-01-01

    Plants naturally cycle amino acids across root cell plasma membranes, and any net efflux is termed exudation. The dominant ecological view is that microorganisms and roots passively compete for amino acids in the soil solution, yet the innate capacity of roots to recover amino acids present in ecologically relevant concentrations is unknown. We find that, in the absence of culturable microorganisms, the influx rates of 16 amino acids (each supplied at 2.5 μm) exceed efflux rates by 5% to 545% in roots of alfalfa (Medicago sativa), Medicago truncatula, maize (Zea mays), and wheat (Triticum aestivum). Several microbial products, which are produced by common soil microorganisms such as Pseudomonas bacteria and Fusarium fungi, significantly enhanced the net efflux (i.e. exudation) of amino acids from roots of these four plant species. In alfalfa, treating roots with 200 μm phenazine, 2,4-diacetylphloroglucinol, or zearalenone increased total net efflux of 16 amino acids 200% to 2,600% in 3 h. Data from 15N tests suggest that 2,4-diacetylphloroglucinol blocks amino acid uptake, whereas zearalenone enhances efflux. Thus, amino acid exudation under normal conditions is a phenomenon that probably reflects both active manipulation and passive uptake by microorganisms, as well as diffusion and adsorption to soil, all of which help overcome the innate capacity of plant roots to reabsorb amino acids. The importance of identifying potential enhancers of root exudation lies in understanding that such compounds may represent regulatory linkages between the larger soil food web and the internal carbon metabolism of the plant. PMID:15347793

  4. Gut microbiome and metabolic syndrome.

    Science.gov (United States)

    Mazidi, Mohsen; Rezaie, Peyman; Kengne, Andre Pascal; Mobarhan, Majid Ghayour; Ferns, Gordon A

    2016-01-01

    The gut microbiome contributes approximately 2kg of the whole body weight, and recent studies suggest that gut microbiota has a profound effect on human metabolism, potentially contributing to several features of the metabolic syndrome. Metabolic syndrome is defined by a clustering of metabolic disorders that include central adiposity with visceral fat accumulation, dyslipidemia, insulin resistance, dysglycemia and non-optimal blood pressure levels. Metabolic syndrome is associated with an increased risk of cardiovascular diseases and type 2 diabetes. It is estimated that around 20-25 percent of the world's adult population has metabolic syndrome. In this manuscript, we have reviewed the existing data linking gut microbiome with metabolic syndrome. Existing evidence from studies both in animals and humans support a link between gut microbiome and various components of metabolic syndrome. Possible pathways include involvement with energy homeostasis and metabolic processes, modulation of inflammatory signaling pathways, interferences with the immune system, and interference with the renin-angiotensin system. Modification of gut microbiota via prebiotics, probiotics or other dietary interventions has provided evidence to support a possible beneficial effect of interventions targeting gut microbiota modulation to treat components or complications of metabolic syndrome.

  5. Serum amino acid profiles and their alterations in colorectal cancer.

    Science.gov (United States)

    Leichtle, Alexander Benedikt; Nuoffer, Jean-Marc; Ceglarek, Uta; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin

    2012-08-01

    Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.

  6. Transport of aromatic amino acids by Brevibacterium linens.

    OpenAIRE

    Boyaval, P; Moreira, E; Desmazeaud, M. J.

    1983-01-01

    Whole metabolizing Brevibacterium linens cells were used to study the transport of aromatic amino acids. Kinetic results followed the Michaelis-Menten equation with apparent Km values for phenylalanine, tyrosine, and tryptophan of 24, 3.5, and 1.8 microM. Transport of these amino acids was optimum at pH 7.5 and 25 degrees C for phenylalanine and pH 8.0 and 35 degrees C for tyrosine and tryptophan. Crossed inhibitions were all noncompetitive. The only marked stereospecificity was for the L for...

  7. α-Amino Acid-Isosteric α-Amino Tetrazoles

    NARCIS (Netherlands)

    Zhao, Ting; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Herdtweck, Eberhardt; Dömling, Alexander

    2016-01-01

    The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection c

  8. Radiation-induced increase in the release of amino acids by isolated, perfused skeletal muscle

    International Nuclear Information System (INIS)

    Local exposure of the hindquarter of the rat to 15Gy of gamma-radiation resulted, 4-6h after irradiation, in increased release of amino acids by the isolated, perfused hindquarter preparation, 70% of which is skeletal muscle. This increase in release involves not only alanine and glutamine, but also those amino acids not metabolized by muscle and, therefore, released in proportion to their occurrence in muscle proteins. Because metabolic parameters and content of energy-rich phosphate compounds in muscle remain unchanged, it is unlikely that general cellular damage is the underlying cause of the radiation-induced increase in amino acid release. The findings strongly favour the hypothesis that increased availability of amino acids results from enhanced protein break-down in skeletal muscle which has its onset shortly after irradiation. This radiation-induced disturbance in protein metabolism might be one of the pathogenetic factors in the aetiology of radiation myopathy. (author)

  9. tRNAs: cellular barcodes for amino acids

    DEFF Research Database (Denmark)

    Banerjee, Rajat; Chen, Shawn; Dare, Kiley;

    2010-01-01

    The role of tRNA in translating the genetic code has received considerable attention over the last 50 years, and we now know in great detail how particular amino acids are specifically selected and brought to the ribosome in response to the corresponding mRNA codon. Over the same period, it has...... also become increasingly clear that the ribosome is not the only destination to which tRNAs deliver amino acids, with processes ranging from lipid modification to antibiotic biosynthesis all using aminoacyl-tRNAs as substrates. Here we review examples of alternative functions for tRNA beyond...... translation, which together suggest that the role of tRNA is to deliver amino acids for a variety of processes that includes, but is not limited to, protein synthesis....

  10. Amino acids in Arctic aerosols

    Directory of Open Access Journals (Sweden)

    E. Scalabrin

    2012-07-01

    Full Text Available Amino acids are significant components of atmospheric aerosols, affecting organic nitrogen input to marine ecosystems, atmospheric radiation balance, and the global water cycle. The wide range of amino acid reactivities suggest that amino acids may serve as markers of atmospheric transport and deposition of particles. Despite this potential, few measurements have been conducted in remote areas to assess amino acid concentrations and potential sources. Polar regions offer a unique opportunity to investigate atmospheric processes and to conduct source apportionment studies of such compounds. In order to better understand the importance of amino acid compounds in the global atmosphere, we determined free amino acids (FAAs in seventeen size-segregated aerosol samples collected in a polar station in the Svalbard Islands from 19 April until 14 September 2010. We used an HPLC coupled with a tandem mass spectrometer (ESI-MS/MS to analyze 20 amino acids to quantify compounds at fmol m−3 levels. Mean total FAA concentration was 1070 fmol m−3 where serine and glycine were the most abundant compounds in almost all samples and accounted for 45–60% of the total amino acid relative abundance. The other eighteen compounds had average concentrations between 0.3 and 98 fmol m−3. The higher amino acid concentrations were present in the ultrafine aerosol fraction (<0.49 μm and accounted for the majority of the total amino acid content. Local marine sources dominate the boreal summer amino acid concentrations, with the exception of the regional input from Icelandic volcanics.

  11. Plasma free amino acid kinetics in rainbow trout (Oncorhynchus mykiss) using a bolus injection of 15N-labeled amino acids.

    Science.gov (United States)

    Robinson, Jacob William; Yanke, Dan; Mirza, Jeff; Ballantyne, James Stuart

    2011-02-01

    To gain insight into the metabolic design of the amino acid carrier systems in fish, we injected a bolus of (15)N amino acids into the dorsal aorta in mature rainbow trout (Oncorhynchus mykiss). The plasma kinetic parameters including concentration, pool size, rate of disappearance (R(d)), half-life and turnover rate were determined for 15 amino acids. When corrected for metabolic rate, the R(d) values obtained for trout for most amino acids were largely comparable to human values, with the exception of glutamine (which was lower) and threonine (which was higher). R(d) values ranged from 0.9 μmol 100 g(-1) h(-1) (lysine) to 22.1 μmol 100 g(-1) h(-1) (threonine) with most values falling between 2 and 6 μmol 100 g(-1) h(-1). There was a significant correlation between R(d) and the molar proportion of amino acids in rainbow trout whole body protein hydrolysate. Other kinetic parameters did not correlate significantly with whole body amino acid composition. This indicates that an important design feature of the plasma-free amino acids system involves proportional delivery of amino acids to tissues for protein synthesis.

  12. Metabolic Disorders

    Science.gov (United States)

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  13. Genome scale engineering techniques for metabolic engineering.

    Science.gov (United States)

    Liu, Rongming; Bassalo, Marcelo C; Zeitoun, Ramsey I; Gill, Ryan T

    2015-11-01

    Metabolic engineering has expanded from a focus on designs requiring a small number of genetic modifications to increasingly complex designs driven by advances in genome-scale engineering technologies. Metabolic engineering has been generally defined by the use of iterative cycles of rational genome modifications, strain analysis and characterization, and a synthesis step that fuels additional hypothesis generation. This cycle mirrors the Design-Build-Test-Learn cycle followed throughout various engineering fields that has recently become a defining aspect of synthetic biology. This review will attempt to summarize recent genome-scale design, build, test, and learn technologies and relate their use to a range of metabolic engineering applications.

  14. Artificial Metalloenzymes through Chemical Modification of Engineered Host Proteins

    KAUST Repository

    Zernickel, Anna

    2014-10-01

    With a few exceptions, all organisms are restricted to the 20 canonical amino acids for ribosomal protein biosynthesis. Addition of new amino acids to the genetic code can introduce novel functionalities to proteins, broadening the diversity of biochemical as well as chemical reactions and providing new tools to study protein structure, reactivity, dynamics and protein-protein-interactions. The site directed in vivo incorporation developed by P. G. SCHULTZ and coworkers, using an archeal orthogonal tRNA/aaRS (aminoacyl-tRNA synthase) pair, allows site-specifically insertion of a synthetic unnatural amino acid (UAA) by reprogramming the amber TAG stop codon. A variety of over 80 different UAAs can be introduced by this technique. However by now a very limited number can form kinetically stable bonds to late transition metals. This thesis aims to develop new catalytically active unnatural amino acids or strategies for a posttranslational modification of site-specific amino acids in order to achieve highly enantioselective metallorganic enzyme hybrids (MOEH). As a requirement a stable protein host has to be established, surviving the conditions for incorporation, posttranslational modification and the final catalytic reactions. mTFP* a fluorescent protein was genetically modified by excluding any exposed Cys, His and Met forming a variant mTFP*, which fulfills the required specifications. Posttranslational chemical modification of mTFP* allow the introduction of single site metal chelating moieties. For modification on exposed cysteines different maleiimid containing ligand structures were synthesized. In order to perform copper catalyzed click reactions, suitable unnatural amino acids (para-azido-(L)-phenylalanine, para-ethynyl-(L)-phenylalanine) were synthesized and a non-cytotoxic protocol was established. The triazole ring formed during this reaction may contribute as a moderate σ-donor/π-acceptor ligand to the metal binding site. Since the cell limits the

  15. 补充支链氨基酸对失眠老年大鼠行为和糖代谢的影响%Effects of branched-chain amino acids supplementation on behaviour and glucose metabolism in aged rats subjected to in- somnia(

    Institute of Scientific and Technical Information of China (English)

    欧阳儒颖; 张济生; 蔡懿灵

    2014-01-01

    Objectives To explore the effects of branched-chain amino acids( BCAA) supplementation on behaviour and glucose metabolism in aged rats subjected to isomnia.Methods Experimental model of isomnia was established by use of sleep deprivation method(flower pot),thirty aged male rats were divided into five groups randomly:C(control)group, 6h(6 hours sleep per day) group, 6hB(6 hours sleep per day and fed fodder enriched with BCAA)group,4h(4 hours sleep per day)group and 4hB group.Re-sults Time of resting on the center lattic,number of make-up and number of excrete were significantly increased in experimental groups compared with C group(PC group>4h group(P0.05).Conpared with C group,the level of FPG in experimential groups were increased apparently (P4h (P<0.05).Conclusions supplementation of BCAA may ameliorates behavior and glucose metabolism in aged rats subjected to isomnia.%目的:探讨补充支链氨基酸( branched-chain amino acids,BCAA)对失眠老年大鼠行为和糖代谢的影响。方法采用小平台水环境的睡眠剥夺方法建立动物失眠模型,30只雄性老年大鼠随机分为对照组( C组)、6h组(每天6小时睡眠组)、6hB组(每天睡眠6小时,进食添加BCAA的饲料),4h组(每天睡眠4小时),4hB组(每天睡眠4小时,进食添加BCAA的饲料)。结果实验组大鼠的修饰行为次数、中央格停留时间、粪便颗粒数均高于C组,差异具有显著性( P<0.05)。且修饰行为次数、中央格停留时间4hB组<4h组(P<0.05);旷场实验得分6h组>C组>4h组,差异具有显著性(P<0.05)。但旷场实验得分、粪便颗粒数6h组与6hB组,4h组与4hB组比较无差异(P>0.05)。与C组比较,实验组的FPG水平显著升高(P<0.05);但4hB组<4h组(P<0.05)。与C组比较4h组和4hB组的血清INS水平显著升高(P<0.05),且4hB组<4h组(P<0.05)。与C组比较,

  16. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    Science.gov (United States)

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  17. The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health

    Directory of Open Access Journals (Sweden)

    Henrieta Škovierová

    2016-10-01

    Full Text Available Homocysteine (Hcy is a sulfur-containing non-proteinogenic amino acid derived in methionine metabolism. The increased level of Hcy in plasma, hyperhomocysteinemia, is considered to be an independent risk factor for cardio and cerebrovascular diseases. However, it is still not clear if Hcy is a marker or a causative agent of diseases. More and more research data suggest that Hcy is an important indicator for overall health status. This review represents the current understanding of molecular mechanism of Hcy metabolism and its link to hyperhomocysteinemia-related pathologies in humans. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated protein, nucleic acid and carbohydrate oxidation and lipoperoxidation, products known to be involved in cytotoxicity. Additionally, we examine the role of Hcy in thiolation of proteins, which results in their molecular and functional modifications. We also highlight the relationship between the imbalance in Hcy metabolism and pathogenesis of diseases, such as cardiovascular diseases, neurological and psychiatric disorders, chronic kidney disease, bone tissue damages, gastrointestinal disorders, cancer, and congenital defects.

  18. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    Science.gov (United States)

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  19. Microfluidics in amino acid analysis.

    Science.gov (United States)

    Pumera, Martin

    2007-07-01

    Microfluidic devices have been widely used to derivatize, separate, and detect amino acids employing many different strategies. Virtually zero-dead volume interconnections and fast mass transfer in small volume microchannels enable dramatic increases in on-chip derivatization reaction speed, while only minute amounts of sample and reagent are needed. Due to short channel path, fast subsecond separations can be carried out. With sophisticated miniaturized detectors, the whole analytical process can be integrated on one platform. This article reviews developments of lab-on-chip technology in amino acid analysis, it shows important design features such as sample preconcentration, precolumn and postcolumn amino acid derivatization, and unlabeled and labeled amino acid detection with focus on advanced designs. The review also describes important biomedical and space exploration applications of amino acid analysis on microfluidic devices. PMID:17542043

  20. Genetics of metabolic resistance.

    Science.gov (United States)

    Richter, Otto; Langemann, Dirk; Beffa, Roland

    2016-09-01

    Herbicide resistance has become a major issue for many weeds. Metabolic resistance refers to the biochemical processes within organisms that degrade herbicides to less toxic compounds, resulting in a shift of the dose response curve. This type of resistance involves polygenic inheritance. A model is presented linking the biochemical pathway of amino acid synthesis and the detoxifying pathway of an inhibitor of the key enzyme ALS. From this model, resistance factors for each biotype are derived, which are then applied to a polygenic population genetic model for an annual weed plant. Polygenic inheritance is described by a new approach based on tensor products of heredity matrices. Important results from the model are that low dose regimes favour fast emergence of resistant biotypes and that the emergence of resistant biotypes occurs as abrupt outbreaks. The model is used to evaluate strategies for the management of metabolic resistance. PMID:27424952

  1. A compendium of inborn errors of metabolism mapped onto the human metabolic network.

    Science.gov (United States)

    Sahoo, Swagatika; Franzson, Leifur; Jonsson, Jon J; Thiele, Ines

    2012-10-01

    Inborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism. Using literary data, we reconstructed an AC/FAO module consisting of 352 reactions and 139 metabolites. When this module was combined with the human metabolic reconstruction, the synthesis of 39 acylcarnitines and 22 amino acids, which are routinely measured, was captured and 235 distinct IEMs could be mapped. We collected phenotypic and clinical features for each IEM enabling comprehensive classification. We found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ. Furthermore, we analyzed the IEMs in the context of metabolic network topology to gain insight into common features between metabolically connected IEMs. While many known examples were identified, we discovered some surprising IEM pairs that shared reactions as well as clinical features but not necessarily causal genes. Moreover, we could also re-confirm that acetyl-CoA acts as a central metabolite. This network based analysis leads to further insight of hot spots in human metabolism with respect to IEMs. The presented comprehensive knowledge base of IEMs will provide a valuable tool in studying metabolic changes involved in inherited metabolic diseases. PMID:22699794

  2. The seasonal fluctuation of plasma amino acids in aquarium-maintained bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Miyaji, Kazuki; Ohta, Mitsuaki; Nagao, Kenji; Ohtani, Nobuyo; Bannai, Makoto

    2012-07-01

    Although there has been extensive research on plasma amino acid profiles of mammals, there is currently a lack of information on seasonal differences in the concentrations of plasma amino acids specifically in cetaceans. The present study examined the response of the plasma amino acids to seasonal changes in the culture environment after controlling for the effect of sex and age. Significant seasonal changes in plasma carnosine (P=0.012), cystine (P=0.0014), isoleucine (P=0.0042), methionine (P=0.002), ornithine (P=0.0096), and taurine (P=0.032) were observed. These amino acids were mainly related to capacity for exercise, ammonia detoxification, thermoregulation, and osmoregulation. We proposed that optimizing plasma amino acids levels by supplementation of amino acids should be of considerable benefit for aquarium-maintained bottlenose dolphins. This study constitutes a first step towards improving our understanding of the metabolism of aquarium-maintained bottlenose dolphins. We also revealed that the ratio of tryptophan to large neutral amino acids significantly declined (P=0.0076), suggesting reduction in serotonin synthesis in winter and autumn. Although further studies are needed, this finding implied that bottlenose dolphins could produce behavioral changes seasonally by the alteration of serotonin activity. To better understand the metabolic machinery for amino acids that facilitate the adaptation of marine mammals to their environments, it is essential to continue monitoring of and further investigations into relationships between plasma amino acids and specific environmental factors. PMID:22333514

  3. The effect of dispensable amino acids on nitrogen and amino acid losses in Atlantic salmon (Salmo salar) fry fed a protein-free diet

    OpenAIRE

    Abboudi, T.; Mambrini, M.; Larondelle, Y.; Rollin, X.

    2009-01-01

    The nutritional role of dispensable amino acids (DAAs) has been seldom studied in fish, while the metabolism of these species is orientated toward the oxidation of amino acids (AAs) for energetic purpose. The objective of this study was to characterize the role of DAAs in the absence of indispensable (1) AA supply in Atlantic salmon and to verify if, as in mammals they play a nutritional role under near maintenance conditions. Therefore we measured the effect of adding DAAs on nitrogen and AA...

  4. Effects of Lipolysacchride on Amino Acid Composition and Gene Expressions Related to Protein Metabolism in Milk of Dairy Cows%脂多糖对泌乳奶牛乳中氨基酸组成及蛋白质代谢相关基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    臧长江; 张养东; 王加启; 胡涛; 卜登攀; 金迪; 周凌云; 李发弟

    2012-01-01

    本试验旨在通过半体内和体外试验研究灌注脂多糖(lipopolysacchride,LPS)对泌乳奶牛乳中氨基酸组成和蛋白质代谢相关基因表达的影响.半体内试验选用6头经产的荷斯坦奶牛[泌乳天数为(186±30) d],随机分为对照组和试验组,每组3头.采用交叉试验设计,每期正试期7d,间隔期14 d;试验组阴外动脉灌注LPS(大肠杆菌型O111∶B4,0.01μg/kg),对照组阴外动脉灌注生理盐水.体外试验以乳腺上皮细胞为模型,基础培养基中LPS添加水平分别为0、0.1和10.0 ng/mL,培养24 h后,采用实时定量-PCR(qRT-PCR)法检测目的基因的相对表达水平.结果表明,阴外动脉灌注LPS后,乳中必需氨基酸、支链氨基酸含量随着灌注时间的增加呈先升高后降低的趋势(P>0.05),灌注后6h达到最高;乳中非必需氨基酸含量随着灌注时间的增加呈先降低后升高的趋势(P>0.05),灌注后6h达到最低.LPS提高了乳腺上皮细胞中p70核糖体蛋白S6激酶-1(S6K1)和真核起始因子4E结合蛋白-1(4EBP1)mRNA的表达水平(P>0.05),且具有剂量效应.LPS对雷帕霉素靶点(mTOR)、Janus激酶2(JAK2)mRNA表达水平影响差异不显著(P>0.05),但有提高的趋势.与对照组相比,LPS显著提高了信号转导和转录激活因子5(STAT5)mRNA表达水平(P<0.05).综上所述,LPS通过干扰mTOR通路和JAK2/STAT5通路影响了乳蛋白及氨基酸组成.%The objective of this experiment was to study the effects of infusion lipopolysacchride (LPS) on the amino acid composition and gene expressions related to protein metabolism in milk of dairy cows by semi in vivo and in vitro tests. Six multipara Holstein lactating cows [days in milk were (186 ±30) d] were selected in the in vivo test, and randomly divided into experimental and control groups with three cows in each group. A cross test design was applied. The test consisted of two experimental periods (7 d each) and an interval period (14 d). Cows in the

  5. Human Rights and Behavior Modification

    Science.gov (United States)

    Roos, Philip

    1974-01-01

    Criticisms of behavior modification, which charge that it violates ethical and legal principles, are discussed and reasons are presented to explain behavior modification's susceptibility to attack. (GW)

  6. α-Amino Acid-Isosteric α-Amino Tetrazoles.

    Science.gov (United States)

    Zhao, Ting; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Herdtweck, Eberhardt; Dömling, Alexander

    2016-02-24

    The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field. PMID:26817531

  7. Amino Acids from a Comet

    Science.gov (United States)

    Cook, Jamie Elisla

    2009-01-01

    NASA's Stardust spacecraft returned samples from comet 81P/Wild 2 to Earth in January 2006. Examinations of the organic compounds in cometary samples can reveal information about the prebiotic organic inventory present on the early Earth and within the early Solar System, which may have contributed to the origin of life. Preliminary studies of Stardust material revealed the presence of a suite of organic compounds including several amines and amino acids, but the origin of these compounds (cometary- vs. terrestrial contamination) could not be identified. We have recently measured the carbon isotopic ratios of these amino acids to determine their origin, leading to the first detection of a coetary amino acid.

  8. Transgenic manipulation of a single polyamine in poplar cells affects the accumulation of all amino acids.

    Science.gov (United States)

    Mohapatra, Sridev; Minocha, Rakesh; Long, Stephanie; Minocha, Subhash C

    2010-04-01

    The polyamine metabolic pathway is intricately connected to metabolism of several amino acids. While ornithine and arginine are direct precursors of putrescine, they themselves are synthesized from glutamate in multiple steps involving several enzymes. Additionally, glutamate is an amino group donor for several other amino acids and acts as a substrate for biosynthesis of proline and gamma-aminobutyric acid, metabolites that play important roles in plant development and stress response. Suspension cultures of poplar (Populus nigra x maximowiczii), transformed with a constitutively expressing mouse ornithine decarboxylase gene, were used to study the effect of up-regulation of putrescine biosynthesis (and concomitantly its enhanced catabolism) on cellular contents of various protein and non-protein amino acids. It was observed that up-regulation of putrescine metabolism affected the steady state concentrations of most amino acids in the cells. While there was a decrease in the cellular contents of glutamine, glutamate, ornithine, arginine, histidine, serine, glycine, cysteine, phenylalanine, tryptophan, aspartate, lysine, leucine and methionine, an increase was seen in the contents of alanine, threonine, valine, isoleucine and gamma-aminobutyric acid. An overall increase in percent cellular nitrogen and carbon content was also observed in high putrescine metabolizing cells compared to control cells. It is concluded that genetic manipulation of putrescine biosynthesis affecting ornithine consumption caused a major change in the entire ornithine biosynthetic pathway and had pleiotropic effects on other amino acids and total cellular carbon and nitrogen, as well. We suggest that ornithine plays a key role in regulating this pathway.

  9. The transcription factor AREB1 regulates primary metabolic pathways in tomato fruits.

    Science.gov (United States)

    Bastías, Adriana; Yañez, Mónica; Osorio, Sonia; Arbona, Vicent; Gómez-Cadenas, Aurelio; Fernie, Alisdair R; Casaretto, José A

    2014-06-01

    Tomato fruit development is regulated both by the action of plant hormones and by tight genetic control. Recent studies suggest that abscisic acid (ABA) signalling may affect different aspects of fruit maturation. Previously, it was shown that SlAREB1, an ABA-regulated transcription factor involved in stress-induced responses, is expressed in seeds and in fruit tissues in tomato. Here, the role of SlAREB1 in regulating the expression of genes relevant for primary metabolic pathways and affecting the metabolic profile of the fruit was investigated using transgenic tomato lines. Metabolite profiling using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and non-targeted liquid chromatography-mass spectrometry (LC-MS) was performed on pericarp tissue from fruits harvested at three stages of fruit development. Principal component analysis of the data could distinguish the metabolite profiles of non-transgenic fruits from those that overexpress and down-regulate SlAREB1. Overexpression of SlAREB1 resulted in increased content of organic acids, hexoses, hexose-phosphates, and amino acids in immature green, mature green, and red ripe fruits, and these modifications correlated with the up-regulation of enzyme-encoding genes involved in primary carbohydrate and amino acid metabolism. A non-targeted LC-MS analysis indicated that the composition of secondary metabolites is also affected in transgenic lines. In addition, gene expression data revealed that some genes associated with fruit ripening are also up-regulated in SlAREB1-overexpressing lines compared with wild-type and antisense lines. Taken together, the results suggest that SlAREB1 participates in the regulation of the metabolic programming that takes place during fruit ripening and that may explain part of the role of ABA in fruit development in tomato.

  10. 40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino substituted triazine amino... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato...

  11. Asparagine Metabolic Pathways in Arabidopsis.

    Science.gov (United States)

    Gaufichon, Laure; Rothstein, Steven J; Suzuki, Akira

    2016-04-01

    Inorganic nitrogen in the form of ammonium is assimilated into asparagine via multiple steps involving glutamine synthetase (GS), glutamate synthase (GOGAT), aspartate aminotransferase (AspAT) and asparagine synthetase (AS) in Arabidopsis. The asparagine amide group is liberated by the reaction catalyzed by asparaginase (ASPG) and also the amino group of asparagine is released by asparagine aminotransferase (AsnAT) for use in the biosynthesis of amino acids. Asparagine plays a primary role in nitrogen recycling, storage and transport in developing and germinating seeds, as well as in vegetative and senescence organs. A small multigene family encodes isoenzymes of each step of asparagine metabolism in Arabidopsis, except for asparagine aminotransferase encoded by a single gene. The aim of this study is to highlight the structure of the genes and encoded enzyme proteins involved in asparagine metabolic pathways; the regulation and role of different isogenes; and kinetic and physiological properties of encoded enzymes in different tissues and developmental stages. PMID:26628609

  12. Skeletal muscle metabolism in hypokinetic rats

    Science.gov (United States)

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  13. Involvement of the Neutral Amino Acid Transporter SLC6A15 and Leucine in Obesity-Related Phenotypes

    OpenAIRE

    Jana Drgonova; Jacobsson, Josefin A.; Han, Joan C.; Yanovski, Jack A.; Robert Fredriksson; Claude Marcus; Schiöth, Helgi B; Uhl, George R.

    2013-01-01

    Brain pathways, including those in hypothalamus and nucleus of the solitary tract, influence food intake, nutrient preferences, metabolism and development of obesity in ways that often differ between males and females. Branched chain amino acids, including leucine, can suppress food intake, alter metabolism and change vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent transporter of leucine and other branched chain amino acids that is expressed by neurons in hypothal...

  14. 2-Amino-5-chloropyridinium nitrate

    Directory of Open Access Journals (Sweden)

    Donia Zaouali Zgolli

    2009-11-01

    Full Text Available The title structure, C5H6ClN2+·NO3−, is held together by extensive hydrogen bonding between the NO3− ions and 2-amino-5-chloropyridinium H atoms. The cation–anion N—H...O hydrogen bonds link the ions into a zigzag- chain which develops parallel to the b axis. The structure may be compared with that of the related 2-amino-5-cyanopyridinium nitrate.

  15. Readers of PCNA modifications.

    Science.gov (United States)

    Ulrich, Helle D; Takahashi, Tomio

    2013-08-01

    The eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), acts as a central coordinator of DNA transactions by providing a multivalent interaction surface for factors involved in DNA replication, repair, chromatin dynamics and cell cycle regulation. Posttranslational modifications (PTMs), such as mono- and polyubiquitylation, sumoylation, phosphorylation and acetylation, further expand the repertoire of PCNA's binding partners. These modifications affect PCNA's activity in the bypass of lesions during DNA replication, the regulation of alternative damage processing pathways such as homologous recombination and DNA interstrand cross-link repair, or impact on the stability of PCNA itself. In this review, we summarise our current knowledge about how the PTMs are "read" by downstream effector proteins that mediate the appropriate action. Given the variety of interaction partners responding to PCNA's modified forms, the ensemble of PCNA modifications serves as an instructive model for the study of biological signalling through PTMs in general. PMID:23580141

  16. Structural dynamic modification

    Indian Academy of Sciences (India)

    A Sestieri

    2000-06-01

    Vibration and acoustic requirements are becoming increasingly important in the design of mechanical structures, but they are not usually of primary concern in the design process. So the need to vary the structural behaviour to solve noise and vibration problems often occurs at the prototype stage, giving rise to the so-called structural modification problem. In this paper, the direct problem of determing the new response of a system, after some modifications are introduced into the sestem, is analysed using two different databases: the modal database and the frequency response function database. The limitaions of the modal database are discussed. Structural modifications that can be accounted for are lumped masses, springs, dampers and dynamic absorbers.

  17. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolism....... The aim of this article is to provide knowledge of nucleotide metabolism and its regulation to facilitate interpretation of data arising from genetics, proteomics, and transcriptomics in connection with biotechnological processes and beyond....

  18. Trend analysis of the correlation of amino acid plasma profile with glycemic status in Saudi diabetic patients

    Directory of Open Access Journals (Sweden)

    Fahad A. Al-Abbasi

    2012-10-01

    Full Text Available The role of amino acids in diabetes mellitus and its metabolic traits have been suggested previously; however, studied to a very limited scale in the Saudi patient population. Patients diagnosed with diabetes mellitus were included in the current clinical study. Sample was representative and in accordance with the national population distribution. Blood samples were drawn and assayed for glucose, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein. General biochemical markers, such as alkaline phosphatase (ALP, creatinine kinase (CK, aspartate transaminase (AST, alanine transaminase (ALT and blood urea nitrogen (BUN were assessed. Serum amino acids of different categories (essential, semi-essential and metabolic indicator amino acids were assessed. Correlation co-efficient between each amino acid and serum glucose level was calculated. The current study showed positive correlation between amino acid level and glucose serum concentration in male while it showed negative correlation in female Saudi diabetic patients. Male patients had significantly higher methionine concentration parallel to their glycemic status. Metabolic indicator amino acids significantly changed in concordance with the glycemic status of female patients more than in male patients. In conclusion, serum amino acid is positively correlated with glycemic status in Saudi male diabetic patients while negatively correlated in female patients. Yet, further study would be recommended to utilize serum amino acid profile as surrogate parameter for the metabolic complications of diabetes mellitus.

  19. Metabolic ecology.

    Science.gov (United States)

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

    Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

  20. Genetics of homocysteine metabolism and associated disorders

    Directory of Open Access Journals (Sweden)

    S. Brustolin

    2010-01-01

    Full Text Available Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, an essential amino acid, and is metabolized by one of two pathways: remethylation or transsulfuration. Abnormalities of these pathways lead to hyperhomocysteinemia. Hyperhomocysteinemia is observed in approximately 5% of the general population and is associated with an increased risk for many disorders, including vascular and neurodegenerative diseases, autoimmune disorders, birth defects, diabetes, renal disease, osteoporosis, neuropsychiatric disorders, and cancer. We review here the correlation between homocysteine metabolism and the disorders described above with genetic variants on genes coding for enzymes of homocysteine metabolism relevant to clinical practice, especially common variants of the MTHFR gene, 677C>T and 1298A>C. We also discuss the management of hyperhomocysteinemia with folic acid supplementation and fortification of folic acid and the impact of a decrease in the prevalence of congenital anomalies and a decline in the incidence of stroke mortality.

  1. Functional amino acids in nutrition and health.

    Science.gov (United States)

    Wu, Guoyao

    2013-09-01

    The recent years have witnessed growing interest in biochemistry, physiology and nutrition of amino acids (AA) in growth, health and disease of humans and other animals. This results from the discoveries of AA in cell signaling involving protein kinases, G protein-coupled receptors, and gaseous molecules (i.e., NO, CO and H2S). In addition, nutritional studies have shown that dietary supplementation with several AA (e.g., arginine, glutamine, glutamate, leucine, and proline) modulates gene expression, enhances growth of the small intestine and skeletal muscle, or reduces excessive body fat. These seminal findings led to the new concept of functional AA, which are defined as those AA that participate in and regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of the organisms. Functional AA hold great promise in prevention and treatment of metabolic diseases (e.g., obesity, diabetes, and cardiovascular disorders), intrauterine growth restriction, infertility, intestinal and neurological dysfunction, and infectious disease (including viral infections).

  2. Organic modification of carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The organic modification of carbon nanotubes is a novel research field being developed recently. In this article, the history and newest progress of organic modification of carbon nanotubes are reviewed from two aspects:organic covalent modification and organic noncovalent modification of carbon nanotubes. The preparation and properties of organic modified carbon nanotubes are discussed in detail. In addition, the prospective development of organic modification of carbon nanotubes is suggested.

  3. Behavior Modification with Children

    Science.gov (United States)

    Brown, Daniel G.

    1972-01-01

    The author urges wider use of positive reinforcement theories in helping emotionally disturbed and mentally handicapped children. Underlining the influence of environment on behavior, he also notes that behavior modification programs utilize fewer trained personnel more effectively and, like Tennessee's Re-Education Treatment, allow for therapy in…

  4. Defining Behavior Modification

    Science.gov (United States)

    Christoplos, Florence; Valletutti, Peter

    1969-01-01

    Discusses the proposition that: "The educational problem involved in behavior modification, in the evaluationand measurement of learning, is the integration and coordination of three types of information affecting the achievement of specific behavioral goals: (1) information about the child, (2) information about the task, and (3) information…

  5. Context modification in action

    NARCIS (Netherlands)

    Visser, A.

    2008-01-01

    In this paper we develop the positive fragment of Context Modification Logic. This logical system is a variant of Dynamic Predicate Logic that employs multiple-access variables and that treats argument places in the same way as Latin. The positive fragment is purely incremental.

  6. Degradation of Arginine and Other Amino Acids by Eubacterium nodatum ATCC 33099

    OpenAIRE

    Uematsu, H.; Hoshino, E.

    2011-01-01

    The utilisation of a total of 20 amino acids by Eubacterium nodatum, a predominant asaccharolytic anaerobe isolated from human periodontal pockets, was studied. Washed cells of the microorganism produced substantial amounts of acetate, butyrate and ammonia from lysine, and butyrate and ammonia from arginine as main products under anaerobic conditions. They also produced a small amount of formate from histidine. Metabolic products were not detected from any of the other 17 amino acids. These r...

  7. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status.

    Science.gov (United States)

    Melnik, Bodo C; Schmitz, Gerd; John, Swen; Carrera-Bastos, Pedro; Lindeberg, Staffan; Cordain, Loren

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual's pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  8. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

    Science.gov (United States)

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual’s pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  9. Deciphering transcriptional and metabolic networks associated with lysine metabolism during Arabidopsis seed development.

    Science.gov (United States)

    Angelovici, Ruthie; Fait, Aaron; Zhu, Xiaohong; Szymanski, Jedrzej; Feldmesser, Ester; Fernie, Alisdair R; Galili, Gad

    2009-12-01

    In order to elucidate transcriptional and metabolic networks associated with lysine (Lys) metabolism, we utilized developing Arabidopsis (Arabidopsis thaliana) seeds as a system in which Lys synthesis could be stimulated developmentally without application of chemicals and coupled this to a T-DNA insertion knockout mutation impaired in Lys catabolism. This seed-specific metabolic perturbation stimulated Lys accumulation starting from the initiation of storage reserve accumulation. Our results revealed that the response of seed metabolism to the inducible alteration of Lys metabolism was relatively minor; however, that which was observable operated in a modular manner. They also demonstrated that Lys metabolism is strongly associated with the operation of the tricarboxylic acid cycle while largely disconnected from other metabolic networks. In contrast, the inducible alteration of Lys metabolism was strongly associated with gene networks, stimulating the expression of hundreds of genes controlling anabolic processes that are associated with plant performance and vigor while suppressing a small number of genes associated with plant stress interactions. The most pronounced effect of the developmentally inducible alteration of Lys metabolism was an induction of expression of a large set of genes encoding ribosomal proteins as well as genes encoding translation initiation and elongation factors, all of which are associated with protein synthesis. With respect to metabolic regulation, the inducible alteration of Lys metabolism was primarily associated with altered expression of genes belonging to networks of amino acids and sugar metabolism. The combined data are discussed within the context of network interactions both between and within metabolic and transcriptional control systems.

  10. Uptake and conversion of D-amino acids in Arabidopsis thaliana.

    Science.gov (United States)

    Gördes, Dirk; Kolukisaoglu, Üner; Thurow, Kerstin

    2011-02-01

    The D-enantiomers of proteinogenic amino acids fulfill essential functions in bacteria, fungi and animals. Just in the plant kingdom, the metabolism and role of D-amino acids (D-AAs) still remains unclear, although plants have to cope with significant amounts of these compounds from microbial decay in the rhizosphere. To fill this gap of knowledge, we tested the inhibitory effects of D-AAs on plant growth and established a method to quantitate 16 out of 19 proteinogenic amino acids and their D-enantiomers in plant tissue extracts. Therefore, the amino acids in the extracts were derivatized with Marfey's reagent and separated by HPLC-MS. We used two ecotypes (Col-0 and C24) and a mutant (lht1) of the model plant Arabidopsis thaliana to determine the influence and fate of exogenously applied D-AAs. All of them were found in high concentrations in the plant extracts after application, even in lht1, which points to additional transporters facilitating the import of D-AAs. The addition of particular amino acids (D-Trp, D-Phe, D-Met and D-His) led to the accumulation of the corresponding L-amino acid. In almost all cases, the application of a D-AA resulted in the accumulation of D-Ala and D-Glu. The presented results indicate that soil borne D-AAs can actively be taken up and metabolized via central metabolic routes.

  11. Influence of Wastewater Discharge on the Metabolic Potential of the Microbial Community in River Sediments

    KAUST Repository

    Li, Dong

    2015-09-24

    To reveal the variation of microbial community functions during water filtration process in river sediments, which has been utilized widely in natural water treatment systems, this study investigates the influence of municipal wastewater discharge to streams on the phylotype and metabolic potential of the microbiome in upstream and particularly various depths of downstream river sediments. Cluster analyses based on both microbial phylogenetic and functional data collectively revealed that shallow upstream sediments grouped with those from deeper subsurface downstream regions. These sediment samples were distinct from those found in shallow downstream sediments. Functional genes associated with carbohydrate, xenobiotic, and certain amino acid metabolisms were overrepresented in upstream and deep downstream samples. In contrast, the more immediate contact with wastewater discharge in shallow downstream samples resulted in an increase in the relative abundance of genes associated with nitrogen, sulfur, purine and pyrimidine metabolisms, as well as restriction–modification systems. More diverse bacterial phyla were associated with upstream and deep downstream sediments, mainly including Actinobacteria, Planctomycetes, and Firmicutes. In contrast, in shallow downstream sediments, genera affiliated with Betaproteobacteria and Gammaproteobacteria were enriched with putative functions that included ammonia and sulfur oxidation, polyphosphate accumulation, and methylotrophic bacteria. Collectively, these results highlight the enhanced capabilities of microbial communities residing in deeper stream sediments for the transformation of water contaminants and thus provide a foundation for better design of natural water treatment systems to further improve the removal of contaminants. © 2015, Springer Science+Business Media New York.

  12. Influence of Wastewater Discharge on the Metabolic Potential of the Microbial Community in River Sediments.

    Science.gov (United States)

    Li, Dong; Sharp, Jonathan O; Drewes, Jörg E

    2016-01-01

    To reveal the variation of microbial community functions during water filtration process in river sediments, which has been utilized widely in natural water treatment systems, this study investigates the influence of municipal wastewater discharge to streams on the phylotype and metabolic potential of the microbiome in upstream and particularly various depths of downstream river sediments. Cluster analyses based on both microbial phylogenetic and functional data collectively revealed that shallow upstream sediments grouped with those from deeper subsurface downstream regions. These sediment samples were distinct from those found in shallow downstream sediments. Functional genes associated with carbohydrate, xenobiotic, and certain amino acid metabolisms were overrepresented in upstream and deep downstream samples. In contrast, the more immediate contact with wastewater discharge in shallow downstream samples resulted in an increase in the relative abundance of genes associated with nitrogen, sulfur, purine and pyrimidine metabolisms, as well as restriction-modification systems. More diverse bacterial phyla were associated with upstream and deep downstream sediments, mainly including Actinobacteria, Planctomycetes, and Firmicutes. In contrast, in shallow downstream sediments, genera affiliated with Betaproteobacteria and Gammaproteobacteria were enriched with putative functions that included ammonia and sulfur oxidation, polyphosphate accumulation, and methylotrophic bacteria. Collectively, these results highlight the enhanced capabilities of microbial communities residing in deeper stream sediments for the transformation of water contaminants and thus provide a foundation for better design of natural water treatment systems to further improve the removal of contaminants.

  13. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome...... suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells....... Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival, and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation...

  14. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  15. Catabolism of Branched Chain Amino Acids Supports Respiration but Not Volatile Synthesis in Tomato Fruits

    Institute of Scientific and Technical Information of China (English)

    Andrej Kochevenko; Wagner L.Araújo; Gregory S.Maloney; Denise M.Tieman; Phuc Thi Do; Mark G.Taylor; Harry J.Klee; Alisdair R.Fernie

    2012-01-01

    The branched-chain amino acid transaminases (BCATs) have a crucial role in metabolism of the branched-chain amino acids leucine,isoleucine,and valine.These enzymes catalyze the last step of synthesis and the initial step of degradation of these amino acids.Although the biosynthetic pathways of branched chain amino acids in plants have been extensively investigated and a number of genes have been characterized,their catabolism in plants is not yet completely understood.We previously characterized the branched chain amino acid transaminase gene family in tomato,revealing both the subcellular localization and kinetic properties of the enzymes encoded by six genes.Here,we examined possible functions of the enzymes during fruit development.We further characterized transgenic plants differing in the expression of branched chain amino acid transaminases 1 and 3,evaluating the rates of respiration in fruits deficient in BCAT1 and the levels of volatiles in lines overexpressing either BCAT1 or BCAT3.We quantitatively tested,via precursor and isotope feeding experiments,the importance of the branched chain amino acids and their corresponding keto acids in the formation of fruit volatiles.Our results not only demonstrate for the first time the importance of branched chain amino acids in fruit respiration,but also reveal that keto acids,rather than amino acids,are the likely precursors for the branched chain flavor volatiles.

  16. Enzymatic modification of starch

    DEFF Research Database (Denmark)

    Jensen, Susanne Langgård

    while others were able to largely retain granular structure. All products were, though, modified with regard to chain length distribution, which indicated an increased degree of branching. Also all products showed a decrease in molecular size. The products, which remained granular, were found to show......In the food industry approaches for using bioengineering are investigated as alternatives to conventional chemical and physical starch modification techniques in development of starches with specific properties. Enzyme-assisted post-harvest modification is an interesting approach to this, since...... substrate concentration (30-40% dry matter (DM)) and high enzyme activity (750-2250 BE units (BEU)/g sample). Starches from various botanical sources, representing a broad range of properties, were used as substrates. The effects of the used conditions on the BE-reaction were evaluated by characterization...

  17. Pectin modifications: a review.

    Science.gov (United States)

    Chen, Jun; Liu, Wei; Liu, Cheng-Mei; Li, Ti; Liang, Rui-Hong; Luo, Shun-Jing

    2015-01-01

    In recent years, the interest in studying modification of pectin has increased. A number of hydroxyl and carboxyl groups distributed along the backbone as well as a certain amount of neutral sugars presented as side chains make pectin capable of preparing a broad spectrum of derivatives. By forming pectin derivatives, their properties may be modified and some other new functional properties may be created. This article attempts to review the information about various methods used for pectin modification, including substitution (alkylation, amidation, quaternization, thiolation, sulfation, oxidation, etc.), chain elongation (cross-linking and grafting) and depolymerization (chemical, physical, and enzymatic degradation). Characteristics and applications of some pectin derivatives are also presented. In addition, the safety and regulatory status of pectin and its derivatives were reviewed.

  18. Metabolic encephalopathies.

    Science.gov (United States)

    Angel, Michael J; Young, G Bryan

    2011-11-01

    Kinnier Wilson coined the term metabolic encephalopathy to describe a clinical state of global cerebral dysfunction induced by systemic stress that can vary in clinical presentation from mild executive dysfunction to deep coma with decerebrate posturing; the causes are numerous. Some mechanisms by which cerebral dysfunction occurs in metabolic encephalopathies include focal or global cerebral edema, alterations in transmitter function, the accumulation of uncleared toxic metabolites, postcapillary venule vasogenic edema, and energy failure. This article focuses on common causes of metabolic encephalopathy, and reviews common causes, clinical presentations and, where relevant, management.

  19. Geometrically Consistent Mesh Modification

    KAUST Repository

    Bonito, A.

    2010-01-01

    A new paradigm of adaptivity is to execute refinement, coarsening, and smoothing of meshes on manifolds with incomplete information about their geometry and yet preserve position and curvature accuracy. We refer to this collectively as geometrically consistent (GC) mesh modification. We discuss the concept of discrete GC, show the failure of naive approaches, and propose and analyze a simple algorithm that is GC and accuracy preserving. © 2010 Society for Industrial and Applied Mathematics.

  20. Amino acid starvation has opposite effects on mitochondrial and cytosolic protein synthesis.

    Directory of Open Access Journals (Sweden)

    Mark A Johnson

    Full Text Available Amino acids are essential for cell growth and proliferation for they can serve as precursors of protein synthesis, be remodelled for nucleotide and fat biosynthesis, or be burnt as fuel. Mitochondria are energy producing organelles that additionally play a central role in amino acid homeostasis. One might expect mitochondrial metabolism to be geared towards the production and preservation of amino acids when cells are deprived of an exogenous supply. On the contrary, we find that human cells respond to amino acid starvation by upregulating the amino acid-consuming processes of respiration, protein synthesis, and amino acid catabolism in the mitochondria. The increased utilization of these nutrients in the organelle is not driven primarily by energy demand, as it occurs when glucose is plentiful. Instead it is proposed that the changes in the mitochondrial metabolism complement the repression of cytosolic protein synthesis to restrict cell growth and proliferation when amino acids are limiting. Therefore, stimulating mitochondrial function might offer a means of inhibiting nutrient-demanding anabolism that drives cellular proliferation.

  1. Proteins, Peptides and Amino Acids: Role in Infant Nutrition.

    Science.gov (United States)

    Nutten, Sophie

    2016-01-01

    Proteins are polymers composed of 30 or more amino acids; some of them are essential dietary components, since they are not synthetized by human metabolic processes. They are crucial for healthy growth and development and influence major functions of the body. The infant's first year is a critical time of rapid growth and development, which must be supported by a high rate of protein synthesis. Breast milk, as a single specific food source in the first months of life, is providing the total protein and essential amino acids required. Infant formulas have been designed for infants who cannot be breastfed. They should be similar to breast milk in their composition and their functional outcomes, insuring appropriate growth, optimal development, maturation of the immune system, easy digestion and healthy metabolic programming. By modifying their protein components, specific infant formulas have also been developed for specific needs. For example, partially hydrolyzed (prevention of atopic dermatitis) and extensively hydrolyzed or amino-acid-based infant formulas (reduction in allergy symptoms) have been designed for the management of cow's milk protein allergy. In conclusion, proteins provided via breast milk or infant formula are essential components of the infant's diet; therefore, the specific quality, quantity and conformation of proteins are of utmost importance for healthy growth and development.

  2. Proteins, Peptides and Amino Acids: Role in Infant Nutrition.

    Science.gov (United States)

    Nutten, Sophie

    2016-01-01

    Proteins are polymers composed of 30 or more amino acids; some of them are essential dietary components, since they are not synthetized by human metabolic processes. They are crucial for healthy growth and development and influence major functions of the body. The infant's first year is a critical time of rapid growth and development, which must be supported by a high rate of protein synthesis. Breast milk, as a single specific food source in the first months of life, is providing the total protein and essential amino acids required. Infant formulas have been designed for infants who cannot be breastfed. They should be similar to breast milk in their composition and their functional outcomes, insuring appropriate growth, optimal development, maturation of the immune system, easy digestion and healthy metabolic programming. By modifying their protein components, specific infant formulas have also been developed for specific needs. For example, partially hydrolyzed (prevention of atopic dermatitis) and extensively hydrolyzed or amino-acid-based infant formulas (reduction in allergy symptoms) have been designed for the management of cow's milk protein allergy. In conclusion, proteins provided via breast milk or infant formula are essential components of the infant's diet; therefore, the specific quality, quantity and conformation of proteins are of utmost importance for healthy growth and development. PMID:27336588

  3. Metabolism and transport of gamma-carboxyglutamic acid.

    Science.gov (United States)

    Shah, D V; Tews, J K; Harper, A E; Suttie, J W

    1978-03-01

    gamma-Carboxyglutamic acid residues have beeh shown to be present in prothrombin, the other vitamin K-dependent clotting factors, and more recently in bone and kidney proteins. This amino acid is formed by a posttranslational vitamin K-dependent carboxylation of glutamyl residues in polypeptide precursors of these protens. It has now been demonstrated that this amino acid, either in the free or peptide-bound form, is not metabolically degraded by the rat, but is quantitatively excreted in the urine. In nephrectomized rats, the tissue concentration of intravenously administered gamma-carboxyglutamic acid is increased, but there is still no evidence of any oxidative metabolism of this amino acid. These amino acid is transported by kidney slices against a concentration gradient, but does not accumulate in liver, intestinal or brain tissues. Preliminary data suggest that gamma-carboxyglutamic acid may be concentrated by a carrier system different from that utilized by other amino acids. PMID:629998

  4. Development of a kinetic metabolic model: application to Catharanthus roseus hairy root

    OpenAIRE

    Leduc, M.; Tikhomiroff, C.; Cloutier, M.; Perrier, M.; Jolicoeur, M.

    2006-01-01

    A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independe...

  5. The importance of serine metabolism in cancer.

    Science.gov (United States)

    Mattaini, Katherine R; Sullivan, Mark R; Vander Heiden, Matthew G

    2016-08-01

    Serine metabolism is frequently dysregulated in cancers; however, the benefit that this confers to tumors remains controversial. In many cases, extracellular serine alone is sufficient to support cancer cell proliferation, whereas some cancer cells increase serine synthesis from glucose and require de novo serine synthesis even in the presence of abundant extracellular serine. Recent studies cast new light on the role of serine metabolism in cancer, suggesting that active serine synthesis might be required to facilitate amino acid transport, nucleotide synthesis, folate metabolism, and redox homeostasis in a manner that impacts cancer. PMID:27458133

  6. NMR-based metabonomic analyses of the effects of ultrasmall superparamagnetic particles of iron oxide (USPIO) on macrophage metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (China); Zhao Jing [China Institute of Atomic Energy (China); Hao Fuhua [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (China); Chen Chang [Institute of Biophysics, The Chinese Academy of Sciences, National Laboratory of Biomacromolecules (China); Bhakoo, Kishore [Singapore Bioimaging Consortium Agency for Science, Technology and Research (A-STAR) (Singapore); Tang, Huiru, E-mail: huiru.tang@wipm.ac.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics (China)

    2011-05-15

    The metabonomic changes in murine RAW264.7 macrophage-like cell line induced by ultrasmall superparamagnetic particles of iron oxides (USPIO) have been investigated, by analyzing both the cells and culture media, using high-resolution NMR in conjunction with multivariate statistical methods. Upon treatment with USPIO, macrophage cells showed a significant decrease in the levels of triglycerides, essential amino acids such as valine, isoleucine, and choline metabolites together with an increase of glycerophospholipids, tyrosine, phenylalanine, lysine, glycine, and glutamate. Such cellular responses to USPIO were also detectable in compositional changes of cell media, showing an obvious depletion of the primary nutrition molecules, such as glucose and amino acids and the production of end-products of glycolysis, such as pyruvate, acetate, and lactate and intermediates of TCA cycle such as succinate and citrate. At 48 h treatment, there was a differential response to incubation with USPIO in both cell metabonome and medium components, indicating that USPIO are phagocytosed and released by macrophages. Furthermore, information on cell membrane modification can be derived from the changes in choline-like metabolites. These results not only suggest that NMR-based metabonomic methods have sufficient sensitivity to identify the metabolic consequences of murine RAW264.7 macrophage-like cell line response to USPIO in vitro, but also provide useful information on the effects of USPIO on cellular metabolism.

  7. Predicting lysine phosphoglycerylation with fuzzy SVM by incorporating k-spaced amino acid pairs into Chou׳s general PseAAC.

    Science.gov (United States)

    Ju, Zhe; Cao, Jun-Zhe; Gu, Hong

    2016-05-21

    As a new type of post-translational modification, lysine phosphoglycerylation plays a key role in regulating glycolytic process and metabolism in cells. Due to the traditional experimental methods are time-consuming and labor-intensive, it is important to develop computational methods to identify the potential phosphoglycerylation sites. However, the prediction performance of the existing phosphoglycerylation site predictor is not satisfactory. In this study, a novel predictor named CKSAAP_PhoglySite is developed to predict phosphoglycerylation sites by using composition of k-spaced amino acid pairs and fuzzy support vector machine. On the one hand, after many aspects of assessments, we find the composition of k-spaced amino acid pairs is more suitable for representing the protein sequence around the phosphoglycerylation sites than other encoding schemes. On the other hand, the proposed fuzzy support vector machine algorithm can effectively handle the imbalanced and noisy problem in phosphoglycerylation sites training dataset. Experimental results indicate that CKSAAP_PhoglySite outperforms the existing phosphoglycerylation site predictor Phogly-PseAAC significantly. A matlab software package for CKSAAP_PhoglySite can be freely downloaded from https://github.com/juzhe1120/Matlab_Software/blob/master/CKSAAP_PhoglySite_Matlab_Software.zip. PMID:26908349

  8. Metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gogia Atul

    2006-02-01

    Full Text Available The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entitiy. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes, hypertriglyceridemia, hypertension, polycystic ovary yndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely

  9. Lipid Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  10. Combinatorics of aliphatic amino acids.

    Science.gov (United States)

    Grützmann, Konrad; Böcker, Sebastian; Schuster, Stefan

    2011-01-01

    This study combines biology and mathematics, showing that a relatively simple question from molecular biology can lead to complicated mathematics. The question is how to calculate the number of theoretically possible aliphatic amino acids as a function of the number of carbon atoms in the side chain. The presented calculation is based on earlier results from theoretical chemistry concerning alkyl compounds. Mathematical properties of this number series are highlighted. We discuss which of the theoretically possible structures really occur in living organisms, such as leucine and isoleucine with a chain length of four. This is done both for a strict definition of aliphatic amino acids only involving carbon and hydrogen atoms in their side chain and for a less strict definition allowing sulphur, nitrogen and oxygen atoms. While the main focus is on proteinogenic amino acids, we also give several examples of non-proteinogenic aliphatic amino acids, playing a role, for instance, in signalling. The results are in agreement with a general phenomenon found in biology: Usually, only a small number of molecules are chosen as building blocks to assemble an inconceivable number of different macromolecules as proteins. Thus, natural biological complexity arises from the multifarious combination of building blocks.

  11. Studies on the chemical modification of goat liver cystatin and the effect on its anti-papain inhibitory activity.

    Science.gov (United States)

    Shah, Aaliya; Aatif, Mohammad; Priyadarshini, Medha; Khan, Mohd Shahnawaz; Amin, Fakhra; Bano, Bilqees

    2012-11-01

    Goat liver cystatin was subjected to various chemical modifications in order to ascertain the amino acid residues responsible for its structural and functional integrity. Modification of tryptophan by HNBB led to the complete inactivation of the protein. The inactivation was also accompanied by the complete loss of tryptophan fluorescence at 340 nm. The reaction of liver cystatin with HNBB yielded a characteristic decrease in absorbance at 280 nm. Acetylation of the amino groups of liver cystatin was carried out in the presence of acetic anhydride. The acetylated cystatin showed a decrease in fluorescence intensity at 335 nm which could be attributed to the modification of tyrosine residue due to side reaction.

  12. Animal metabolism

    International Nuclear Information System (INIS)

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  13. Metabolism during hypodynamia

    Science.gov (United States)

    Federov, I. V.

    1980-01-01

    Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

  14. Amalyse modifications during production and application

    DEFF Research Database (Denmark)

    Nielsen, Connie

    I value can be identified when analysing the final enzyme product, hereby indicating that the protein is modified. The purpose of the present Ph.D. project is to identify differences between the multiple forms of a-amylase derived from the same gene and determine if or how these various modifications...... of these modified sites was evaluated by characterisation of BLA variants with single site specific mutations. The BLA variants with mutations mimicking deamidations in the active site and in the substrate binding cleft were found to influence the kinetic parameters (kcat and KM) in different ways. The wash...... performance was also influenced by these mutations though these effects were mainly positive. Modified Lys and Arg residues suspected to be involved in substrate binding of longer substrates or secondary binding sites were evaluated by site specific mutations to amino acids with neutral side chains...

  15. Improvement of activity and stability of chloroperoxidase by chemical modification

    Directory of Open Access Journals (Sweden)

    Wang Min

    2007-05-01

    Full Text Available Abstract Background Enzymes show relative instability in solvents or at elevated temperature and lower activity in organic solvent than in water. These limit the industrial applications of enzymes. Results In order to improve the activity and stability of chloroperoxidase, chloroperoxidase was modified by citraconic anhydride, maleic anhydride or phthalic anhydride. The catalytic activities, thermostabilities and organic solvent tolerances of native and modified enzymes were compared. In aqueous buffer, modified chloroperoxidases showed similar Km values and greater catalytic efficiencies kcat/Km for both sulfoxidation and oxidation of phenol compared to native chloroperoxidase. Of these modified chloroperoxidases, citraconic anhydride-modified chloroperoxidase showed the greatest catalytic efficiency in aqueous buffer. These modifications of chloroperoxidase increased their catalytic efficiencies for sulfoxidation by 12%~26% and catalytic efficiencies for phenol oxidation by 7%~53% in aqueous buffer. However, in organic solvent (DMF, modified chloroperoxidases had lower Km values and higher catalytic efficiencies kcat/Km than native chloroperoxidase. These modifications also improved their thermostabilities by 1~2-fold and solvent tolerances of DMF. CD studies show that these modifications did not change the secondary structure of chloroperoxidase. Fluorescence spectra proved that these modifications changed the environment of tryptophan. Conclusion Chemical modification of epsilon-amino groups of lysine residues of chloroperoxidase using citraconic anhydride, maleic anhydride or phthalic anhydride is a simple and powerful method to enhance catalytic properties of enzyme. The improvements of the activity and stability of chloroperoxidase are related to side chain reorientations of aromatics upon both modifications.

  16. Starch: its metabolism, evolution, and biotechnological modification in plants.

    Science.gov (United States)

    Zeeman, Samuel C; Kossmann, Jens; Smith, Alison M

    2010-01-01

    Starch is the most widespread and abundant storage carbohydrate in plants. We depend upon starch for our nutrition, exploit its unique properties in industry, and use it as a feedstock for bioethanol production. Here, we review recent advances in research in three key areas. First, we assess progress in identifying the enzymatic machinery required for the synthesis of amylopectin, the glucose polymer responsible for the insoluble nature of starch. Second, we discuss the pathways of starch degradation, focusing on the emerging role of transient glucan phosphorylation in plastids as a mechanism for solubilizing the surface of the starch granule. We contrast this pathway in leaves with the degradation of starch in the endosperm of germinated cereal seeds. Third, we consider the evolution of starch biosynthesis in plants from the ancestral ability to make glycogen. Finally, we discuss how this basic knowledge has been utilized to improve and diversify starch crops.

  17. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    Science.gov (United States)

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  18. Quantitative amino acid profiling and stable isotopically labeled amino acid tracer enrichment used for in vivo human systemic and tissue kinetics measurements.

    Science.gov (United States)

    Bornø, Andreas; van Hall, Gerrit

    2014-03-01

    An important area within clinical functional metabolomics is in vivo amino acid metabolism and protein turnover measurements for which accurate amino acid concentrations and stable isotopically labeled amino acid enrichments are mandatory not the least when tissue metabolomics is determined. The present study describes a new sensitive liquid chromatography tandem mass-spectrometry method quantifying 20 amino acids and their tracer(s) ([ring-(13)C6]/D5Phenylalanine) in human plasma and skeletal muscle specimens. Before analysis amino acids were extracted and purified via deprotonization/ion exchange, derivatized using a phenylisothiocyanate reagent and each amino acid was quantitated with its own stable isotopically labeled internal standard (uniformly labeled-(13)C/(15)N). The method was validated according to general recommendations for chromatographic analytical methods. The calibration curve correlations for amino acids were on average; r(2)=0.998. Interday accuracy for amino acids determined in spiked plasma was on average 97.3% and the coefficient of variation (CV) was 2.6%. The ([ring-(13)C6]/D5Phenylalanine) enrichment CV's for machine reproducibility in muscle tissue fluid and plasma were 4.4 and 0.8%, and the interday variability was 3.4% and the recovery was 90.5%, respectively. In conclusion, we have developed and validated a method for quantitative amino acid profiling that meets the requirements for systemic and tissue human in vivo amino acid and protein turnover kinetics measurements. Moreover, citrulline, ornithine, π-methyl-histidine, τ-methyl-l-histidine, hydroxy-proline and carnitine were analysed but when similar precision and accuray are required an additional stable istopically labeled internal standard for these meatablites should be be added.

  19. Quinone-amino acid conjugates targeting Leishmania amino acid transporters.

    Science.gov (United States)

    Prati, Federica; Goldman-Pinkovich, Adele; Lizzi, Federica; Belluti, Federica; Koren, Roni; Zilberstein, Dan; Bolognesi, Maria Laura

    2014-01-01

    The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7) to import these nutrients. Probes 1-15 were originated by conjugating cytotoxic quinone fragments (II and III) with amino acids (i.e. arginine and lysine) by means of an amide linkage. The toxicity of the synthesized conjugates against Leishmania extracellular (promastigotes) and intracellular (amastigotes) forms was investigated, as well their inhibition of the relevant amino acid transporters. We observed that some conjugates indeed displayed toxicity against the parasites; in particular, 7 was identified as the most potent derivative (at concentrations of 1 µg/mL and 2.5 µg/mL residual cell viability was reduced to 15% and 48% in promastigotes and amastigotes, respectively). Notably, 6, while retaining the cytotoxic activity of quinone II, displayed no toxicity against mammalian THP1 cells. Transport assays indicated that the novel conjugates inhibited transport activity of lysine, arginine and proline transporters. Furthermore, our analyses suggested that the toxic conjugates might be translocated by the transporters into the cells. The non-toxic probes that inhibited transport competed with the natural substrates for binding to the transporters without being translocated. Thus, it is likely that 6, by exploiting amino acid transporters, can selectively deliver its toxic effects to Leishmania cells. This work provides the first evidence that amino acid transporters of the human pathogen Leishmania might be modulated by small molecules, and warrants their further investigation from drug discovery and chemical biology perspectives. PMID:25254495

  20. Quinone-Amino Acid Conjugates Targeting Leishmania Amino Acid Transporters

    OpenAIRE

    Federica Prati; Adele Goldman-Pinkovich; Federica Lizzi; Federica Belluti; Roni Koren; Dan Zilberstein; Maria Laura Bolognesi

    2014-01-01

    The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7) to import these nutrients. Probes 1-15 were originated by conjugating cytotoxic quinone fragments (II and III) with amino acids (i.e. arginine and lysine) by means of an amide linkage. The toxi...

  1. Quinone-amino acid conjugates targeting Leishmania amino acid transporters.

    Directory of Open Access Journals (Sweden)

    Federica Prati

    Full Text Available The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7 to import these nutrients. Probes 1-15 were originated by conjugating cytotoxic quinone fragments (II and III with amino acids (i.e. arginine and lysine by means of an amide linkage. The toxicity of the synthesized conjugates against Leishmania extracellular (promastigotes and intracellular (amastigotes forms was investigated, as well their inhibition of the relevant amino acid transporters. We observed that some conjugates indeed displayed toxicity against the parasites; in particular, 7 was identified as the most potent derivative (at concentrations of 1 µg/mL and 2.5 µg/mL residual cell viability was reduced to 15% and 48% in promastigotes and amastigotes, respectively. Notably, 6, while retaining the cytotoxic activity of quinone II, displayed no toxicity against mammalian THP1 cells. Transport assays indicated that the novel conjugates inhibited transport activity of lysine, arginine and proline transporters. Furthermore, our analyses suggested that the toxic conjugates might be translocated by the transporters into the cells. The non-toxic probes that inhibited transport competed with the natural substrates for binding to the transporters without being translocated. Thus, it is likely that 6, by exploiting amino acid transporters, can selectively deliver its toxic effects to Leishmania cells. This work provides the first evidence that amino acid transporters of the human pathogen Leishmania might be modulated by small molecules, and warrants their further investigation from drug discovery and chemical biology perspectives.

  2. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  3. RNA modifications by oxidation

    DEFF Research Database (Denmark)

    Poulsen, Henrik E; Specht, Elisabeth; Broedbaek, Kasper;

    2012-01-01

    other RNA molecules show virtually no oxidation. The iron-storage disease hemochromatosis exhibits the most prominent general increase in RNA oxidation ever observed. Oxidation of RNA primarily leads to strand breaks and to oxidative base modifications. Oxidized mRNA is recognized by the ribosomes...... type 2 diabetics; this demonstrates the clinical relevance of RNA oxidation. Taken collectively the available data suggest that RNA oxidation is a contributing factor in several diseases such as diabetes, hemochromatosis, heart failure, and ß-cell destruction. The mechanism involves free iron...

  4. Solitons and ionospheric modification

    Science.gov (United States)

    Sheerin, J. P.; Nicholson, D. R.; Payne, G. L.; Hansen, P. J.; Weatherall, J. C.; Goldman, M. V.

    1982-01-01

    The possibility of Langmuir soliton formation and collapse during ionospheric modification is investigated. Parameters characterizing former facilities, existing facilities, and planned facilities are considered, using a combination of analytical and numerical techniques. At a spatial location corresponding to the exact classical reflection point of the modifier wave, the Langmuir wave evolution is found to be dominated by modulational instability followed by soliton formation and three-dimensional collapse. The earth's magnetic field is found to affect the shape of the collapsing soliton. These results provide an alternative explanation for some recent observations.

  5. Amino acid efflux in the isolated perfused rat pancreas: trans-stimulation by extracellular amino acids.

    Science.gov (United States)

    Mann, G E; Norman, P S; Smith, I C

    1989-01-01

    1. Epithelial uptake and efflux of the non-metabolized system A analogue 2-methylaminoisobutyric acid (MeAIB) and L-serine were studied in the isolated perfused rat pancreas using a dual tracer loading and wash-out technique. Uptakes of 2-[14C]MeAIB and L-[3H]serine were measured relative to D-[3H or 14C]mannitol (extracellular tracer) during a 20 min cell loading period. Maximal uptake for MeAIB (34 +/- 2%, n = 6) occurred within 2-3 min and decreased to 14 +/- 2% after 20 min tracer loading. Uptake for L-serine reached a maximum (62 +/- 4%, n = 7) within 1 min and decreased to 19 +/- 2% after 20 min tracer loading. 2. When tracer wash-out was monitored during subsequent perfusion of the preloaded pancreas with an isotope-free solution, D-mannitol predominantly cleared from a fast exchanging compartment (0.54 +/- 0.05 ml g-1, n = 9) with a time constant (Tfast) of 0.68 +/- 0.04 min. Although MeAIB and L-serine exhibited similar fast phases of wash-out, a much larger efflux occurred from a slowly exchanging pool with respective time constants (Tslow) of 15.47 +/- 0.45 min (n = 6) and 5.98 +/- 0.46 min (n = 7). 3. A rapid vascular challenge of the pancreas with 100 mM-L-serine transiently accelerated cellular efflux of 2-[14C]MeAIB and L-[3H]serine without affecting wash-out of D-[14C]mannitol. Tracer efflux following cell loading with 2-[14C]MeAIB or L-[3H]serine was not stimulated by a challenge with 100 mM-MeAIB. 4. The time course of amino acid evoked 2-[14C]MeAIB and L-[3H]serine efflux paralleled the extracellular dilution profile of a vascular stimulus, suggesting that the acceleration of efflux was due to trans-stimulation. 5. Trans-stimulation of 2-[14C]MeAIB and L-[3H]serine efflux by a further twenty-two naturally occurring and three synthetic amino acids was then examined. L-Proline, N-methyl-DL-alanine, L-lysine and D-lysine selectively stimulated MeAIB efflux. Efflux of both tracer amino acids was accelerated by aminoisobutyric acid (AIB), L-serine, L

  6. [Inherited amino acid transport disorders].

    Science.gov (United States)

    Igarashi, Y; Tada, K

    1992-07-01

    Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush-border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia-hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders. PMID:1404888

  7. Posttranslational Modifications and the Immunogenicity of Biotherapeutics

    Directory of Open Access Journals (Sweden)

    Roy Jefferis

    2016-01-01

    Full Text Available Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs, including quality control (QC in the endoplasmic reticulum (ER and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs both in vivo and in vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA; aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs, a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.

  8. Ethanol metabolism modifies hepatic protein acylation in mice.

    Directory of Open Access Journals (Sweden)

    Kristofer S Fritz

    Full Text Available Mitochondrial protein acetylation increases in response to chronic ethanol ingestion in mice, and is thought to reduce mitochondrial function and contribute to the pathogenesis of alcoholic liver disease. The mitochondrial deacetylase SIRT3 regulates the acetylation status of several mitochondrial proteins, including those involved in ethanol metabolism. The newly discovered desuccinylase activity of the mitochondrial sirtuin SIRT5 suggests that protein succinylation could be an important post-translational modification regulating mitochondrial metabolism. To assess the possible role of protein succinylation in ethanol metabolism, we surveyed hepatic sub-cellular protein fractions from mice fed a control or ethanol-supplemented diet for succinyl-lysine, as well as acetyl-, propionyl-, and butyryl-lysine post-translational modifications. We found mitochondrial protein propionylation increases, similar to mitochondrial protein acetylation. In contrast, mitochondrial protein succinylation is reduced. These mitochondrial protein modifications appear to be primarily driven by ethanol metabolism, and not by changes in mitochondrial sirtuin levels. Similar trends in acyl modifications were observed in the nucleus. However, comparatively fewer acyl modifications were observed in the cytoplasmic or the microsomal compartments, and were generally unchanged by ethanol metabolism. Using a mass spectrometry proteomics approach, we identified several candidate acetylated, propionylated, and succinylated proteins, which were enriched using antibodies against each modification. Additionally, we identified several acetyl and propionyl lysine residues on the same sites for a number of proteins and supports the idea of the overlapping nature of lysine-specific acylation. Thus, we show that novel post-translational modifications are present in hepatic mitochondrial, nuclear, cytoplasmic, and microsomal compartments and ethanol ingestion, and its associated

  9. Ethanol Metabolism Modifies Hepatic Protein Acylation in Mice

    Science.gov (United States)

    Fritz, Kristofer S.; Green, Michelle F.; Petersen, Dennis R.; Hirschey, Matthew D.

    2013-01-01

    Mitochondrial protein acetylation increases in response to chronic ethanol ingestion in mice, and is thought to reduce mitochondrial function and contribute to the pathogenesis of alcoholic liver disease. The mitochondrial deacetylase SIRT3 regulates the acetylation status of several mitochondrial proteins, including those involved in ethanol metabolism. The newly discovered desuccinylase activity of the mitochondrial sirtuin SIRT5 suggests that protein succinylation could be an important post-translational modification regulating mitochondrial metabolism. To assess the possible role of protein succinylation in ethanol metabolism, we surveyed hepatic sub-cellular protein fractions from mice fed a control or ethanol-supplemented diet for succinyl-lysine, as well as acetyl-, propionyl-, and butyryl-lysine post-translational modifications. We found mitochondrial protein propionylation increases, similar to mitochondrial protein acetylation. In contrast, mitochondrial protein succinylation is reduced. These mitochondrial protein modifications appear to be primarily driven by ethanol metabolism, and not by changes in mitochondrial sirtuin levels. Similar trends in acyl modifications were observed in the nucleus. However, comparatively fewer acyl modifications were observed in the cytoplasmic or the microsomal compartments, and were generally unchanged by ethanol metabolism. Using a mass spectrometry proteomics approach, we identified several candidate acetylated, propionylated, and succinylated proteins, which were enriched using antibodies against each modification. Additionally, we identified several acetyl and propionyl lysine residues on the same sites for a number of proteins and supports the idea of the overlapping nature of lysine-specific acylation. Thus, we show that novel post-translational modifications are present in hepatic mitochondrial, nuclear, cytoplasmic, and microsomal compartments and ethanol ingestion, and its associated metabolism, induce specific

  10. Fine-tuning of amino sugar homeostasis by EIIANtr in Salmonella Typhimurium

    Science.gov (United States)

    Yoo, Woongjae; Yoon, Hyunjin; Seok, Yeong-Jae; Lee, Chang-Ro; Lee, Hyung Ho; Ryu, Sangryeol

    2016-01-01

    The nitrogen-metabolic phosphotransferase system, PTSNtr, consists of the enzymes INtr, NPr and IIANtr that are encoded by ptsP, ptsO, and ptsN, respectively. Due to the proximity of ptsO and ptsN to rpoN, the PTSNtr system has been postulated to be closely related with nitrogen metabolism. To define the correlation between PTSNtr and nitrogen metabolism, we performed ligand fishing with EIIANtr as a bait and revealed that D-glucosamine-6-phosphate synthase (GlmS) directly interacted with EIIANtr. GlmS, which converts D-fructose-6-phosphate (Fru6P) into D-glucosamine-6-phosphate (GlcN6P), is a key enzyme producing amino sugars through glutamine hydrolysis. Amino sugar is an essential structural building block for bacterial peptidoglycan and LPS. We further verified that EIIANtr inhibited GlmS activity by direct interaction in a phosphorylation-state-dependent manner. EIIANtr was dephosphorylated in response to excessive nitrogen sources and was rapidly degraded by Lon protease upon amino sugar depletion. The regulation of GlmS activity by EIIANtr and the modulation of glmS translation by RapZ suggest that the genes comprising the rpoN operon play a key role in maintaining amino sugar homeostasis in response to nitrogen availability and the amino sugar concentration in the bacterial cytoplasm. PMID:27628932

  11. Fine-tuning of amino sugar homeostasis by EIIA(Ntr) in Salmonella Typhimurium.

    Science.gov (United States)

    Yoo, Woongjae; Yoon, Hyunjin; Seok, Yeong-Jae; Lee, Chang-Ro; Lee, Hyung Ho; Ryu, Sangryeol

    2016-01-01

    The nitrogen-metabolic phosphotransferase system, PTS(Ntr), consists of the enzymes I(Ntr), NPr and IIA(Ntr) that are encoded by ptsP, ptsO, and ptsN, respectively. Due to the proximity of ptsO and ptsN to rpoN, the PTS(Ntr) system has been postulated to be closely related with nitrogen metabolism. To define the correlation between PTS(Ntr) and nitrogen metabolism, we performed ligand fishing with EIIA(Ntr) as a bait and revealed that D-glucosamine-6-phosphate synthase (GlmS) directly interacted with EIIA(Ntr). GlmS, which converts D-fructose-6-phosphate (Fru6P) into D-glucosamine-6-phosphate (GlcN6P), is a key enzyme producing amino sugars through glutamine hydrolysis. Amino sugar is an essential structural building block for bacterial peptidoglycan and LPS. We further verified that EIIA(Ntr) inhibited GlmS activity by direct interaction in a phosphorylation-state-dependent manner. EIIA(Ntr) was dephosphorylated in response to excessive nitrogen sources and was rapidly degraded by Lon protease upon amino sugar depletion. The regulation of GlmS activity by EIIA(Ntr) and the modulation of glmS translation by RapZ suggest that the genes comprising the rpoN operon play a key role in maintaining amino sugar homeostasis in response to nitrogen availability and the amino sugar concentration in the bacterial cytoplasm. PMID:27628932

  12. Nitrate metabolism in tobacco leaves overexpressing Arabidopsis nitrite reductase.

    Science.gov (United States)

    Davenport, Susie; Le Lay, Pascaline; Sanchez-Tamburrrino, Juan Pablo

    2015-12-01

    Primary nitrogen assimilation in plants includes the reduction of nitrite to ammonium in the chloroplasts by the enzyme nitrite reductase (NiR EC:1.7.7.1) or in the plastids of non-photosynthetic organs. Here we report on a study overexpressing the Arabidopsis thaliana NiR (AtNiR) gene in tobacco plants under the control of a constitutive promoter (CERV - Carnation Etched Ring Virus). The aim was to overexpress AtNiR in an attempt to alter the level of residual nitrite in the leaf which can act as precursor to the formation of nitrosamines. The impact of increasing the activity of AtNiR produced an increase in leaf protein and a stay-green phenotype in the primary transformed AtNiR population. Investigation of the T1 homozygous population demonstrated elevated nitrate reductase (NR) activity, reductions in leaf nitrite and nitrate and the amino acids proline, glutamine and glutamate. Chlorophyl content of the transgenic lines was increased, as evidenced by the stay-green phenotype. This reveals the importance of NiR in primary nitrogen assimilation and how modification of this key enzyme affects both the nitrogen and carbon metabolism of tobacco plants. PMID:26447683

  13. Synthesis of Chiral Amino Cyclic Phosphoric Acids

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Chirai amino cyclic phosphoric acids, 5-amino-2-hydroxy-4- (4-nitrophenyl)-l, 3,2-dioxaphospho- rinane 2-oxide and 2-hydroxy-4- (4-methylsulfonylphenyl)-5-phthalimido-1,3,2-dioxaphos phorinane 2-oxide are synthesized in good over yields (64. 2% and 72. 8% respectively) from 2-amino-l-aryl-l,3-propanediols. The different reaction conditions are necessary in hydrolysis reactions of amino cyclic phosphonyl chlorides.

  14. Amino acid analyses of Apollo 14 samples.

    Science.gov (United States)

    Gehrke, C. W.; Zumwalt, R. W.; Kuo, K.; Aue, W. A.; Stalling, D. L.; Kvenvolden, K. A.; Ponnamperuma, C.

    1972-01-01

    Detection limits were between 300 pg and 1 ng for different amino acids, in an analysis by gas-liquid chromatography of water extracts from Apollo 14 lunar fines in which amino acids were converted to their N-trifluoro-acetyl-n-butyl esters. Initial analyses of water and HCl extracts of sample 14240 and 14298 samples showed no amino acids above background levels.

  15. Unnatural reactive amino acid genetic code additions

    Science.gov (United States)

    Deiters, Alexander; Cropp, T. Ashton; Chin, Jason W.; Anderson, J. Christopher; Schultz, Peter G.

    2014-08-26

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  16. Unnatural reactive amino acid genetic code additions

    Energy Technology Data Exchange (ETDEWEB)

    Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

    2013-05-21

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  17. Amino acids as antioxidants for frying oil

    Science.gov (United States)

    Amino acids, proteins and hydrolysates of proteins have been known to protect edible oils from oxidation. While amino acids and related materials have high potential as antioxidants for frying oil, effectiveness of each amino acid and mechanisms of their activities are not well understood yet. Propo...

  18. Multipolar Electrostatic Energy Prediction for all 20 Natural Amino Acids Using Kriging Machine Learning.

    Science.gov (United States)

    Fletcher, Timothy L; Popelier, Paul L A

    2016-06-14

    A machine learning method called kriging is applied to the set of all 20 naturally occurring amino acids. Kriging models are built that predict electrostatic multipole moments for all topological atoms in any amino acid based on molecular geometry only. These models then predict molecular electrostatic interaction energies. On the basis of 200 unseen test geometries for each amino acid, no amino acid shows a mean prediction error above 5.3 kJ mol(-1), while the lowest error observed is 2.8 kJ mol(-1). The mean error across the entire set is only 4.2 kJ mol(-1) (or 1 kcal mol(-1)). Charged systems are created by protonating or deprotonating selected amino acids, and these show no significant deviation in prediction error over their neutral counterparts. Similarly, the proposed methodology can also handle amino acids with aromatic side chains, without the need for modification. Thus, we present a generic method capable of accurately capturing multipolar polarizable electrostatics in amino acids. PMID:27224739

  19. Metabolic Syndrome

    Science.gov (United States)

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  20. Metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Charles Shaeffer

    2004-01-01

    @@ The emergence of cardiac disease as the number one world-wide cause of death justifies efforts to identify individuals at higher risk for preventive therapy. The metabolic syndrome, originally described by Reaven, 1 has been associated with higher cardiovascular disease risk. 2 Type Ⅱ diabetes is also a frequent sequela. 3

  1. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions are High blood pressure High blood glucose, or blood sugar, levels High levels of triglycerides, a type of fat, in your blood Low ...

  2. Relative Quantification of Sites of Peptide and Protein Modification Using Size Exclusion Chromatography Coupled with Electron Transfer Dissociation

    Science.gov (United States)

    Xie, Boer; Sharp, Joshua S.

    2016-08-01

    One difficult problem in the analysis of peptide modifications is quantifying isomeric modifications that differ by the position of the amino acid modified. HPLC separation using C18 reverse phase chromatography coupled with electron transfer dissociation (ETD) in tandem mass spectrometry has recently been shown to be able to relatively quantify how much of a given modification occurs at each amino acid position for isomeric mixtures; however, the resolution of reverse phase chromatography greatly complicates quantification of isomeric modifications by ETD because of the chromatographic separation of peptides with identical modifications at different sequence positions. Using peptide oxidation as a model system, we investigated the use of size exclusion chromatography coupled with ETD fragmentation to separate peptide sequences. This approach allows for the benefits of chromatographic separation of peptide sequences while ensuring co-elution of modification isomers for accurate relative quantification of modifications using standard data-dependent acquisitions. Using this method, the relative amount of modification at each amino acid can be accurately measured from single ETD MS/MS spectra in a standard data-dependent acquisition experiment.

  3. Relative Quantification of Sites of Peptide and Protein Modification Using Size Exclusion Chromatography Coupled with Electron Transfer Dissociation.

    Science.gov (United States)

    Xie, Boer; Sharp, Joshua S

    2016-08-01

    One difficult problem in the analysis of peptide modifications is quantifying isomeric modifications that differ by the position of the amino acid modified. HPLC separation using C18 reverse phase chromatography coupled with electron transfer dissociation (ETD) in tandem mass spectrometry has recently been shown to be able to relatively quantify how much of a given modification occurs at each amino acid position for isomeric mixtures; however, the resolution of reverse phase chromatography greatly complicates quantification of isomeric modifications by ETD because of the chromatographic separation of peptides with identical modifications at different sequence positions. Using peptide oxidation as a model system, we investigated the use of size exclusion chromatography coupled with ETD fragmentation to separate peptide sequences. This approach allows for the benefits of chromatographic separation of peptide sequences while ensuring co-elution of modification isomers for accurate relative quantification of modifications using standard data-dependent acquisitions. Using this method, the relative amount of modification at each amino acid can be accurately measured from single ETD MS/MS spectra in a standard data-dependent acquisition experiment. Graphical Abstract ᅟ. PMID:27075875

  4. EPIGENETIC MODIFICATIONS OF SWINE GENOME

    OpenAIRE

    Kristina Budimir; Gordana Kralik; Vladimir Margeta

    2013-01-01

    Epigenetics is represents a new way of genome analysis, respectively gene expression that occurs without DNA sequence change. Changes that occur are epigenetic modifications and they include post-translational histone modification and DNA methylation. Chemical groups that are added on DNA molecule cause changes in DNA and create epigenome. The consequence of that is appearance of imprinted genes in genome. Genetic imprinting is epigenetic modification in which one of inherited alleles inactiv...

  5. Evolutionary programming as a platform for in silico metabolic engineering

    OpenAIRE

    Förster Jochen; Rocha Isabel; Patil Kiran; Nielsen Jens

    2005-01-01

    Abstract Background Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms...

  6. Metabolic effects of CO2 anaesthesia in Drosophila melanogaster

    OpenAIRE

    Colinet, H.; Renault, D.

    2012-01-01

    Immobilization of insects is necessary for various experimental purposes, and CO2 exposure remains the most popular anaesthetic method in entomological research. A number of negative side effects of CO2 anaesthesia have been reported, but CO2 probably brings about metabolic modifications that are poorly known. In this work, we used GC/MS-based metabolic fingerprinting to assess the effect of CO2 anaesthesia in Drosophila melanogaster adults. We analysed metabolic variation of flies submitted ...

  7. The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival.

    Directory of Open Access Journals (Sweden)

    João Daniel Santos Fernandes

    Full Text Available Metabolic diversity is an important factor during microbial adaptation to different environments. Among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. Cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. As a result, it faces frequent metabolic shifts and challenges during its life cycle. Here we studied the C. neoformans tryptophan biosynthetic pathway and found that the pathway is essential. RNAi indicated that interruptions in the biosynthetic pathway render strains inviable. However, auxotroph complementation can be partially achieved by tryptophan uptake when a non preferred nitrogen source and lower growth temperature are applied, suggesting that amino acid permeases may be the target of nitrogen catabolism repression (NCR. We used bioinformatics to search for amino acid permeases in the C. neoformans and found eight potential global permeases (AAP1 to AAP8. The transcriptional profile of them revealed that they are subjected to regulatory mechanisms which are known to respond to nutritional status in other fungi, such as (i quality of nitrogen (Nitrogen Catabolism Repression, NCR and carbon sources (Carbon Catabolism Repression, CCR, (ii amino acid availability in the extracellular environment (SPS-sensing and (iii nutritional deprivation (Global Amino Acid Control, GAAC. This study shows that C. neoformans has fewer amino acid permeases than other model yeasts, and that these proteins may be subjected to complex regulatory mechanisms. Our data suggest that the C. neoformans tryptophan biosynthetic pathway is an excellent pharmacological target. Furthermore, inhibitors of this pathway cause Cryptococcus growth arrest in vitro.

  8. Effect of dietary starch level and high rumen-undegradable protein on endocrine-metabolic status, milk yield, and milk composition in dairy cows during early and late lactation.

    Science.gov (United States)

    Piccioli-Cappelli, F; Loor, J J; Seal, C J; Minuti, A; Trevisi, E

    2014-12-01

    Diet composition defines the amount and type of nutrients absorbed by dairy cows. Endocrine-metabolic interactions can influence these parameters, and so nutrient availability for the mammary gland can significantly vary and affect milk yield and its composition. Six dairy cows in early and then late lactation received, for 28 d in a changeover design, 2 diets designed to provide, within the same stage of lactation, similar amounts of rumen fermentable material but either high starch plus sugar (HS) content or low starch plus sugar content (LS). All diets had similar dietary crude protein and calculated supply of essential amino acids. Dry matter intake within each stage of lactation was similar between groups. Milk yield was similar between groups in early lactation, whereas a higher milk yield was observed in late lactation when feeding HS. At the metabolic level, the main difference observed between the diets in both stages of lactation was lower blood glucose in cows fed LS. The lower glucose availability during consumption of LS caused substantial modifications in the circulating and postprandial pattern of metabolic hormones. Feeding LS versus HS resulted in an increase in the ratio of bovine somatotropin to insulin. This increased mobilization of lipid reserves resulted in higher blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, which contributed to the higher milk fat content in both stages of lactation in the LS group. This greater recourse to body fat stores was confirmed by the greater loss of body weight during early lactation and the slower recovery of body weight in late lactation in cows fed LS. The lower insulin to glucagon ratio observed in cows fed LS in early and late lactation likely caused an increase in hepatic uptake and catabolism of amino acids, as confirmed by the higher blood urea concentrations. Despite the higher catabolism of amino acids in LS in early lactation, similar milk protein output was observed for both

  9. Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells.

    Science.gov (United States)

    Lei, Min; Gan, Xianwen; Zhao, Kun; Yu, Qiang; Hu, Lihong

    2015-02-01

    The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity. PMID:25571795

  10. Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells.

    Science.gov (United States)

    Lei, Min; Gan, Xianwen; Zhao, Kun; Yu, Qiang; Hu, Lihong

    2015-02-01

    The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity.

  11. Current topics in the biotechnological production of essential amino acids, functional amino acids, and dipeptides.

    Science.gov (United States)

    Mitsuhashi, Satoshi

    2014-04-01

    Amino acids play important roles in both human and animal nutrition and in the maintenance of health. Here, amino acids are classified into three groups: first, essential amino acids, which are essential to nutrition; second, functional amino acids, recently found to be important in the promotion of physiological functions; and third, dipeptides, which are used to resolve problematic features of specific free amino acids, such as their instability or insolubility. This review focusses on recent researches concerning the microbial production of essential amino acids (lysine and methionine), functional amino acids (histidine and ornithine), and a dipeptide (L-alanyl-L-glutamine). PMID:24679256

  12. Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.

    Science.gov (United States)

    Rardin, Matthew J; Newman, John C; Held, Jason M; Cusack, Michael P; Sorensen, Dylan J; Li, Biao; Schilling, Birgit; Mooney, Sean D; Kahn, C Ronald; Verdin, Eric; Gibson, Bradford W

    2013-04-16

    Large-scale proteomic approaches have identified numerous mitochondrial acetylated proteins; however in most cases, their regulation by acetyltransferases and deacetylases remains unclear. Sirtuin 3 (SIRT3) is an NAD(+)-dependent mitochondrial protein deacetylase that has been shown to regulate a limited number of enzymes in key metabolic pathways. Here, we use a rigorous label-free quantitative MS approach (called MS1 Filtering) to analyze changes in lysine acetylation from mouse liver mitochondria in the absence of SIRT3. Among 483 proteins, a total of 2,187 unique sites of lysine acetylation were identified after affinity enrichment. MS1 Filtering revealed that lysine acetylation of 283 sites in 136 proteins was significantly increased in the absence of SIRT3 (at least twofold). A subset of these sites was independently validated using selected reaction monitoring MS. These data show that SIRT3 regulates acetylation on multiple proteins, often at multiple sites, across several metabolic pathways including fatty acid oxidation, ketogenesis, amino acid catabolism, and the urea and tricarboxylic acid cycles, as well as mitochondrial regulatory proteins. The widespread modification of key metabolic pathways greatly expands the number of known substrates and sites that are targeted by SIRT3 and establishes SIRT3 as a global regulator of mitochondrial protein acetylation with the capability of coordinating cellular responses to nutrient status and energy homeostasis.

  13. Metabolic Syndrome: Hyperlipidemia.

    Science.gov (United States)

    Bragg, Dee Ann Stults; Walling, Anne

    2015-08-01

    Metabolic syndrome is associated with an elevated risk of cardiovascular disease and premature mortality. When metabolic syndrome includes lipid abnormalities, management goals are weight loss and cardiovascular risk management through lifestyle modifications (eg, diet, exercise), and, when appropriate, lowering of lipid levels with pharmacotherapy. Healthy diets are recommended, particularly the Mediterranean diet. Patients also should set a goal of at least 30 minutes of moderate to vigorous exercise on most, preferably all, days of the week. Guidelines provide criteria for statin treatment based on overall cardiovascular risk. High-intensity statin treatment (eg, rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg) typically is recommended unless the patient cannot tolerate therapy. Approximately 5% of patients experience statin-induced myalgia, in which case moderate-intensity treatment can be tried. Lipid levels should be reevaluated 4 to 12 weeks after initiating therapy; lipid levels can be measured without fasting. A lack of improvement often indicates nonadherence. Bile acid sequestrants, fibric acids, and niacin can be used if other drugs are not tolerated. The evidence to support use of integrative medicine is limited, but the strongest evidence of benefit is for garlic (Allium sativum). PMID:26280341

  14. Strategies for comprehensive analysis of amino acid biomarkers of oxidative stress.

    Science.gov (United States)

    Ptolemy, A S; Lee, R; Britz-McKibbin, P

    2007-07-01

    Despite the wide interest in using modified amino acids as putative biomarkers of oxidative stress, many issues remain as to their overall reliability for early detection and diagnosis of diseases. In contrast to conventional single biomarker studies, comprehensive analysis of biomarkers offers an unbiased strategy for global assessment of modified amino acid metabolism due to reactive oxygen and nitrogen species. This review examines recent analytical techniques amenable for analysis of modified amino acids in biological samples reported during 2003-2007. Particular attention is devoted to the need for validated methods applicable to high-throughput analysis of multiple amino acid biomarkers, as well as consideration of sample pretreatment protocols on artifact formation for improved clinical relevance. PMID:17514495

  15. Synthesis and biological properties of amino acids and peptides containing a tetrazolyl moiety

    Science.gov (United States)

    Popova, E. A.; Trifonov, R. E.

    2015-09-01

    Literature data published mainly in the last 15 years on the synthesis and biological properties of amino acid analogues and derivatives containing tetrazolyl moieties are analyzed. Tetrazolyl analogues and derivatives of amino acids and peptides are shown to be promising for medicinal chemistry. Being polynitrogen heterocyclic systems comprising four endocyclic nitrogen atoms, tetrazoles can behave as acids and bases and form strong hydrogen bonds with proton donors (more rarely, with acceptors). They have high metabolic stability and are able to penetrate biological membranes. The review also considers the synthesis and properties of linear and cyclic peptides based on modified amino acids incorporating a tetrazolyl moiety. A special issue is the discussion of the biological properties of tetrazole-containing amino acids and peptides, which exhibit high biological activity and can be used to design new drugs. The bibliography includes 200 references.

  16. Prediction of human protein function from post-translational modifications and localization features

    DEFF Research Database (Denmark)

    Jensen, Lars Juhl; Gupta, Ramneek; Blom, Nikolaj;

    2002-01-01

    a number of functional attributes that are more directly related to the linear sequence of amino acids, and hence easier to predict, than protein structure. These attributes include features associated with post-translational modifications and protein sorting, but also much simpler aspects...

  17. Amino acid properties conserved in molecular evolution.

    Directory of Open Access Journals (Sweden)

    Witold R Rudnicki

    Full Text Available That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts - one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications.

  18. 2-Amino-5-chloropyridinium trifluoroacetate

    Directory of Open Access Journals (Sweden)

    Madhukar Hemamalini

    2010-04-01

    Full Text Available The asymmetric unit of the title salt, C5H6ClN2+·C2F3O2−, contains two independent 2-amino-5-chloropyridinium cations and two independent trifluoroacetate anions. The F atoms of both anions are disordered over two sets of positions, with occupancy ratios of 0.672 (12:0.328 (12 and 0.587 (15:0.413 (15. In the crystal, the cations and anions are linked via N—H...O and C—H...O hydrogen bonds, forming a two-dimensional network parallel to (001.

  19. Pairwise amino acid secondary structural propensities

    Science.gov (United States)

    Chemmama, Ilan E.; Chapagain, Prem P.; Gerstman, Bernard S.

    2015-04-01

    We investigate the propensities for amino acids to form a specific secondary structure when they are paired with other amino acids. Our investigations use molecular dynamics (MD) computer simulations, and we compare the results to those from the Protein Data Bank (PDB). Proper comparison requires weighting of the MD results in a manner consistent with the relative frequency of appearance in the PDB of each possible pair of amino acids. We find that the propensity for an amino acid to assume a secondary structure varies dramatically depending on the amino acid that is before or after it in the primary sequence. This cooperative effect means that when selecting amino acids to facilitate the formation of a secondary structure in peptide engineering experiments, the adjacent amino acids must be considered. We also examine the preference for a secondary structure in bacterial proteins and compare the results to those of human proteins.

  20. Genetically programmed expression of proteins containing the unnatural amino acid phenylselenocysteine

    Science.gov (United States)

    Wang, Jiangyun; Schultz, Peter G.

    2010-09-07

    The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the unnatural amino acid phenylselenocysteine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal aminoacyl-tRNA synthetases, polynucleotides encoding the novel synthetase molecules, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid phenylselenocysteine and translation systems. The invention further provides methods for producing modified proteins (e.g., lipidated proteins) through targeted modification of the phenylselenocysteine residue in a protein.

  1. Effect of dimethylaminoethanol and compound amino acid solution on collagen metabolism and free radicals in D-galactose induced aging rat skin%二甲氨基乙醇和复方氨基酸溶液对衰老大鼠皮肤胶原代谢和自由基的影响

    Institute of Scientific and Technical Information of China (English)

    赵彩玲; 匡瑞霞; 刘肃; 闫丙健

    2014-01-01

    Objective To study the mechanism of anti-aging effect of dimethylaminoethanol (DMAE) and compound amino acid (AA) injection by mesotheray in D-galactose-induced skin aging rat.Methods Eighty rats were randomly divided into aging treatment group (60 cases),aging control group (10 cases) and normal control group (10 cases).The skin aging models were established by subcutaneous infectim of D-galactose.From the 18th day,the aging treatment group were injected intradermally in the rats' both sides hip skin with 0.2% DMAE+ AA,0.1% DMAE+AA,0.2%DMAE,0.1% DMAE,AA,and saline,once a week.After four weeks,HE,water content,superoxide dismutase (SOD) activity,hydroxyproline (HYP) and malondialdehyde (MDA) content were measured.Results Compared with the aging control group,the epidermal and the dermal thickness and the collagen area of rats skin' increased significantly in 0.2 % DMAE+ AA and 0.1% DMAE+ AA treatment groups (P<0.05).0.2% DMAE+AA and 0.1 % DMAE+AA treatment groups also had higher SOD activity,HYP content and lower MDA content than other groups (P<0.05),but no difference was noted among normal control group,0.2% DMAE+AA and 0.1% DMAE+AA group (P>0.05).There were no differences in water content among groups (P>0.05).Conclusions Intradermal injection with 0.1% DMAE+ AA and 0.2 % DMAE+AA in aging rats may increase the epidermal and the dermal thickness and the collagen of rats skin' improve SOD activity,HYP content and decreased MDA content,indicating that it has ability to clear skin free radicals,enhance antioxidant capacity and skin collagen metabolism,and thus prevent skin aging.%目的 探讨真皮内注射二甲氨基乙醇(DMAE)和复方氨基酸溶液(AA)对皮肤胶原代谢和自由基的影响.方法 80只大鼠随机分成衰老治疗组(60只)、衰老对照组(10只)和正常对照组(10只).皮下注射半乳糖制备衰老模型.衰老治疗组从第18天开始,在两侧臀部真皮内分别注射0.2% DMAE+AA、0.1

  2. Correlation between fibroin amino acid sequence and physical silk properties.

    Science.gov (United States)

    Fedic, Robert; Zurovec, Michal; Sehnal, Frantisek

    2003-09-12

    The fiber properties of lepidopteran silk depend on the amino acid repeats that interact during H-fibroin polymerization. The aim of our research was to relate repeat composition to insect biology and fiber strength. Representative regions of the H-fibroin genes were sequenced and analyzed in three pyralid species: wax moth (Galleria mellonella), European flour moth (Ephestia kuehniella), and Indian meal moth (Plodia interpunctella). The amino acid repeats are species-specific, evidently a diversification of an ancestral region of 43 residues, and include three types of regularly dispersed motifs: modifications of GSSAASAA sequence, stretches of tripeptides GXZ where X and Z represent bulky residues, and sequences similar to PVIVIEE. No concatenations of GX dipeptide or alanine, which are typical for Bombyx silkworms and Antheraea silk moths, respectively, were found. Despite different repeat structure, the silks of G. mellonella and E. kuehniella exhibit similar tensile strength as the Bombyx and Antheraea silks. We suggest that in these latter two species, variations in the repeat length obstruct repeat alignment, but sufficiently long stretches of iterated residues get superposed to interact. In the pyralid H-fibroins, interactions of the widely separated and diverse motifs depend on the precision of repeat matching; silk is strong in G. mellonella and E. kuehniella, with 2-3 types of long homogeneous repeats, and nearly 10 times weaker in P. interpunctella, with seven types of shorter erratic repeats. The high proportion of large amino acids in the H-fibroin of pyralids has probably evolved in connection with the spinning habit of caterpillars that live in protective silk tubes and spin continuously, enlarging the tubes on one end and partly devouring the other one. The silk serves as a depot of energetically rich and essential amino acids that may be scarce in the diet. PMID:12816957

  3. Novel Insights into the Diversity of Catabolic Metabolism from Ten Haloarchaeal Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Iain; Scheuner, Carmen; Goker, Markus; Mavromatis, Kostas; Hooper, Sean D.; Porat, Iris; Klenk, Hans-Peter; Ivanova, Natalia; Kyrpides, Nikos

    2011-05-03

    The extremely halophilic archaea are present worldwide in saline environments and have important biotechnological applications. Ten complete genomes of haloarchaea are now available, providing an opportunity for comparative analysis. We report here the comparative analysis of five newly sequenced haloarchaeal genomes with five previously published ones. Whole genome trees based on protein sequences provide strong support for deep relationships between the ten organisms. Using a soft clustering approach, we identified 887 protein clusters present in all halophiles. Of these core clusters, 112 are not found in any other archaea and therefore constitute the haloarchaeal signature. Four of the halophiles were isolated from water, and four were isolated from soil or sediment. Although there are few habitat-specific clusters, the soil/sediment halophiles tend to have greater capacity for polysaccharide degradation, siderophore synthesis, and cell wall modification. Halorhabdus utahensis and Haloterrigena turkmenica encode over forty glycosyl hydrolases each, and may be capable of breaking down naturally occurring complex carbohydrates. H. utahensis is specialized for growth on carbohydrates and has few amino acid degradation pathways. It uses the non-oxidative pentose phosphate pathway instead of the oxidative pathway, giving it more flexibility in the metabolism of pentoses. These new genomes expand our understanding of haloarchaeal catabolic pathways, providing a basis for further experimental analysis, especially with regard to carbohydrate metabolism. Halophilic glycosyl hydrolases for use in biofuel production are more likely to be found in halophiles isolated from soil or sediment.

  4. UV-B stress induced metabolic rearrangements explored with comparative proteomics in three Anabaena species.

    Science.gov (United States)

    Shrivastava, Alok Kumar; Chatterjee, Antra; Yadav, Shivam; Singh, Prashant Kumar; Singh, Shilpi; Rai, L C

    2015-09-01

    Comparative proteomics together with physiological variables revealed different responses among three species of diazotrophic cyanobacterium Anabaena exposed to UV-B stress at the same time points. Perceptible decline in PSII activity, ATP pool, nitrogenase activity and respiration rate was observed for all the three species; this being maximum in Anabaena doliolum, followed by Anabaena sp. PCC 7120 and minimum in Anabaena L31. Statistical analysis of the protein abundance divided majority of them as early accumulated in A. L31, late accumulated in A. sp. PCC 7120 and downregulated in A. doliolum. Tolerance of A. L31 may be ascribed to post-translational modification reflected through the highest number of protein isoforms in its proteome followed by A. PCC 7120 and A. doliolum. Furthermore, increase in abundance of cyanophycinase, glutamine synthetase and succinate semialdehyde dehydrogenase in A. L31 suggests operation of an alternate pathway for assimilation of nitrogen and carbon under UV-B stress. An early accumulation of four proteins viz., glutamate ammonia ligase (Alr2328), transketolase (Alr3344), inorganic pyrophosphatase (All3570), and trigger protein (Alr3681) involved respectively in amino acid metabolism, energy metabolism, biosynthesis of cofactor and trigger protein and chaperone like activity across three species, suggests them to be marker of UV-B stress in Anabaena spp. This article is part of a Special Issue entitled: Proteomics in India.

  5. Global turnover of histone post-translational modifications and variants in human cells

    Directory of Open Access Journals (Sweden)

    Zee Barry M

    2010-12-01

    Full Text Available Abstract Background Post-translational modifications (PTMs on the N-terminal tails of histones and histone variants regulate distinct transcriptional states and nuclear events. Whereas the functional effects of specific PTMs are the current subject of intense investigation, most studies characterize histone PTMs/variants in a non-temporal fashion and very few studies have reported kinetic information about these histone forms. Previous studies have used radiolabeling, fluorescence microscopy and chromatin immunoprecipitation to determine rates of histone turnover, and have found interesting correlations between increased turnover and increased gene expression. Therefore, histone turnover is an understudied yet potentially important parameter that may contribute to epigenetic regulation. Understanding turnover in the context of histone modifications and sequence variants could provide valuable additional insight into the function of histone replacement. Results In this study, we measured the metabolic rate of labeled isotope incorporation into the histone proteins of HeLa cells by combining stable isotope labeling of amino acids in cell culture (SILAC pulse experiments with quantitative mass spectrometry-based proteomics. In general, we found that most core histones have similar turnover rates, with the exception of the H2A variants, which exhibit a wider range of rates, potentially consistent with their epigenetic function. In addition, acetylated histones have a significantly faster turnover compared with general histone protein and methylated histones, although these rates vary considerably, depending on the site and overall degree of methylation. Histones containing transcriptionally active marks have been consistently found to have faster turnover rates than histones containing silent marks. Interestingly, the presence of both active and silent marks on the same peptide resulted in a slower turnover rate than either mark alone on that same

  6. Amino acid uptake in arterio-venous serum of normal and cancerous colon tissues

    Institute of Scientific and Technical Information of China (English)

    Lin-Bo Wang; Jian-Guo Shen; Su-Zhan Zhang; Ke-Feng Ding; Shu Zheng

    2004-01-01

    AIM: To investigate the difference of amino acid uptake between normal and cancerous colon tissues.METHODS: Sixteen patients with colon cancer were enrolled in our study. Blood samples were taken during operations, serum amino acid concentrations of blood from cancerous or normal colon were analyzed. Amino acid uptake rate was calculated by the A-V difference and evaluated statistically.RESULTS: Except for methionine, the uptake rate of amino acids in cancer was higher than that in normal colon (25.01% vs-2.29%, P<0.01). The amino acid uptake rate did not correlate to the size of tumor mass (P>0.05). There was no statistical significance in the amino acid uptake rate according to the Dukes stage, though it was higher in patients with Dukes stage C or D than that with Dukes stage B (P>0.05).CONCLUSION: Abnormal synthetic metabolism of colon cancer may contribute to its higher amino acid uptake rate than that of normal colon.

  7. Plasma amino acid concentrations in 36 dogs with histologically confirmed superficial necrolytic dermatitis.

    Science.gov (United States)

    Outerbridge, Catherine A; Marks, Stanley L; Rogers, Quinton R

    2002-08-01

    Plasma amino acid concentrations were measured in 36 dogs diagnosed with superficial necrolytic dermatitis (SND) via skin biopsy. The median age of the dogs was 10 years, and 27 out of 36 (75%) were male. Twenty-two out of 36 (61%) of the dogs were accounted for by six breeds; West Highland white terriers (six), Shetland sheepdogs (five), cocker spaniels (four), Scottish terriers (three), Lhasa apsos (two) and Border collies (two). The mean concentration (+/- standard deviation) was calculated for each measured plasma amino acid and compared to previously documented concentrations of plasma amino acids measured in dogs with acute and chronic hepatitis. The ratio of branched chain amino acids to aromatic amino acids in the dogs with SND was 2.6, slightly lower than that in normal dogs. The mean plasma amino acid concentrations for dogs with SND were significantly lower than for dogs with acute and chronic hepatitis. A metabolic hepatopathy in which there is increased hepatic catabolism of amino acids is hypothesized to explain the hypoaminoacidaemia seen in SND. PMID:12174180

  8. The effects of the formula of amino acids enriched BCAA on nutritional support in traumatic patients

    Institute of Scientific and Technical Information of China (English)

    Xin-Ying Wang; Ning Li; Jun Gu; Wei-Qin Li; Jie-Shou Li

    2003-01-01

    AIM: To investigate the formula of amino acid enriched BCAA on nutritional support in traumatic patients after operation.METHODS: 40 adult patients after moderate or large abdominal operations were enrolled in a prospective,randomly and single-blind-controlled study, and total parenteral nutrition (TPN) with either formula of amino acid (AA group, 20 cases) or formula of amino acid enriched BCAA (BCAA group, 20 cases). From the second day after operation, total parenteral nutrition was infused to the patients in both groups with equal calorie and equal nitrogen by central or peripheral vein during more than 12 hours per day for 6 days. Meanwhile, nitrogen balance was assayed by collecting 24 hours urine for 6 days. The markers of protein metabolism were investigated such as amino acid patterns, levels of total protein, albumin, prealbumin,transferrin and fibronectin in serum.RESULTS: The positive nitrogen balance in BCAA group occurred two days earlier than that in AA group. The serum levels oftotal protein and albumin in BCAA group were increased more obviously than that in AA group. The concentration of valine was notably increased and the concentration of arginine was markedly decreased in BCAA group after the formula of amino acids enriched BCAA transfusion.CONCLUSION: The formula of amino acid enriched BCAA may normalize the levels of serum amino acids, reduce the proteolysis, increase the synthesis of protein, improve the nutritional status of traumatic patients after operation.

  9. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B;

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  10. Surface modification of cellulose nanocrystals

    Science.gov (United States)

    Eyley, Samuel; Thielemans, Wim

    2014-06-01

    Chemical modification of cellulose nanocrystals is an increasingly popular topic in the literature. This review analyses the type of cellulose nanocrystal modification reactions that have been published in the literature thus far and looks at the steps that have been taken towards analysing the products of the nanocrystal modifications. The main categories of reactions carried out on cellulose nanocrystals are oxidations, esterifications, amidations, carbamations and etherifications. More recently nucleophilic substitutions have been used to introduce more complex functionality to cellulose nanocrystals. Multi-step modifications are also considered. This review emphasizes quantification of modification at the nanocrystal surface in terms of degree of substitution and the validity of conclusions drawn from different analysis techniques in this area. The mechanisms of the modification reactions are presented and considered with respect to the effect on the outcome of the reactions. While great strides have been made in the quality of analytical data published in the field of cellulose nanocrystal modification, there is still vast scope for improvement, both in data quality and the quality of analysis of data. Given the difficulty of surface analysis, cross-checking of results from different analysis techniques is fundamental for the development of reliable cellulose nanocrystal modification techniques.

  11. Surface Modification of Intraocular Lenses

    Directory of Open Access Journals (Sweden)

    Qi Huang

    2016-01-01

    Full Text Available Objective: This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs. Data Sources: All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. Study Selection: The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded. Results: Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol, polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments. Conclusion: The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.

  12. Surface Modification of Intraocular Lenses

    Institute of Scientific and Technical Information of China (English)

    Qi Huang; George Pak-Man Cheng; Kin Chiu; Gui-Qin Wang

    2016-01-01

    Objective:This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs).Data Sources:All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect.Study Selection:The articles on the surface modification of IOLs were included,but those on design modification and surface coating were excluded.Results:Technology of surface modification included plasma,ion beam,layer-by-layer self-assembly,ultraviolet radiation,and ozone.The main molecules introduced into IOLs surface were poly (ethylene glycol),polyhedral oligomeric silsesquioxane,2-methacryloyloxyethyl phosphorylcholine,TiO2,heparin,F-heparin,titanium,titanium nitride,vinyl pyrrolidone,and inhibitors of cytokines.The surface modification either resulted in a more hydrophobic lens,a more hydrophilic lens,or a lens with a hydrophilic anterior and hydrophobic posterior surface.Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments.Conclusion:The surface modification is an efficient,convenient,economic and promising method to improve the biocompatibility ofIOLs.

  13. Stable isotope studies reveal pathways for the incorporation of non-essential amino acids in Acyrthosiphon pisum (pea aphids).

    Science.gov (United States)

    Haribal, Meena; Jander, Georg

    2015-12-01

    Plant roots incorporate inorganic nitrogen into the amino acids glutamine, glutamic acid, asparagine and aspartic acid, which together serve as the primary metabolites of nitrogen transport to other tissues. Given the preponderance of these four amino acids, phloem sap is a nutritionally unbalanced diet for phloem-feeding insects. Therefore, aphids and other phloem feeders typically rely on microbial symbionts for the synthesis of essential amino acids. To investigate the metabolism of the four main transport amino acids by the pea aphid (Acyrthosiphon pisum), and its Buchnera aphidicola endosymbionts, aphids were fed defined diets with stable isotope-labeled glutamine, glutamic acid, asparagine or aspartic acid (U-(13)C, U-(15)N; U-(15)N; α-(15)N; or γ-(15)N). The metabolic fate of the dietary (15)N and (13)C was traced using gas chromatography-mass spectrometry (GC-MS). Nitrogen was the major contributor to the observed amino acid isotopomers with one additional unit mass (M+1). However, there was differential incorporation, with the amine nitrogen of asparagine being incorporated into other amino acids more efficiently than the amide nitrogen. Higher isotopomers (M+2, M+3 and M+4) indicated the incorporation of varying numbers of (13)C atoms into essential amino acids. GC-MS assays also showed that, even with an excess of dietary labeled glutamine, glutamic acid, asparagine or aspartic acid, the overall content of these amino acids in aphid bodies was mostly the product of catabolism of dietary amino acids and subsequent re-synthesis within the aphids. Thus, these predominant dietary amino acids are not passed directly to Buchnera endosymbionts for synthesis of essential amino acids, but are rather are produced de novo, most likely by endogenous aphid enzymes. PMID:26632455

  14. Towards a metabolic therapy of cancer?

    Science.gov (United States)

    Chiu, Martina; Ottaviani, Laura; Bianchi, Massimiliano G; Franchi-Gazzola, Renata; Bussolati, Ovidio

    2012-12-01

    It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely, mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only "metabolic" drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs. PMID:23762991

  15. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  16. Ensemble Modeling of Cancer Metabolism

    Directory of Open Access Journals (Sweden)

    Tahmineh eKhazaei

    2012-05-01

    Full Text Available The metabolic behaviour of cancer cells is adapted to meet their proliferative needs, with notable changes such as enhanced lactate secretion and glucose uptake rates. In this work, we use the Ensemble Modeling (EM framework to gain insight and predict potential drug targets for tumour cells. EM generates a set of models which span the space of kinetic parameters that are constrained by thermodynamics. Perturbation data based on known targets are used to screen the entire ensemble of models to obtain a sub-set, which is increasingly predictive. EM allows for incorporation of regulatory information and captures the behaviour of enzymatic reactions at the molecular level by representing reactions in the elementary reaction form. In this study, a metabolic network consisting of 58 reactions is considered and accounts for glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, and includes allosteric regulation of key enzymes. Experimentally measured intracellular and extracellular metabolite concentrations are used for developing the ensemble of models along with information on established drug targets. The resulting models predicted transaldolase (TALA and succinyl-CoA ligase (SUCOAS1m to cause a significant reduction in growth rate when repressed, relative to currently known drug targets. Furthermore, the results suggest that the synergetic repression of transaldolase and glycine hydroxymethyltransferase (GHMT2r will lead to a three-fold decrease in growth rate compared to the repression of single enzyme targets.

  17. Aspectos atuais sobre aminoácidos de cadeia ramificada e exercício físico Current aspects of branched chain amino acid and exercise

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Rogero

    2008-12-01

    modulation of the immune response, in performance enhancement of individuals who work out in hot environments, and in avoiding muscle lesion. This review approaches all aspects of the metabolism of and supplementation with branched chain amino acids in physical exercise.

  18. Evaluation of the protein metabolism during hepatic coma evidenced by 15N tracer data

    International Nuclear Information System (INIS)

    In patients in coma hepaticum as well as in pigs with experimental hepatic coma the protein metabolism was studied under conditions of parenteral application of an amino acid diet using 15N-glycine as tracer

  19. Identification of a novel amino acid racemase from a hyperthermophilic archaeon Pyrococcus horikoshii OT-3 induced by D-amino acids.

    Science.gov (United States)

    Kawakami, Ryushi; Ohmori, Taketo; Sakuraba, Haruhiko; Ohshima, Toshihisa

    2015-08-01

    To date, there have been few reports analyzing the amino acid requirement for growth of hyperthermophilic archaea. We here found that the hyperthermophilic archaeon Pyrococcus horikoshii OT-3 requires Thr, Leu, Val, Phe, Tyr, Trp, His and Arg in the medium for growth, and shows slow growth in medium lacking Met or Ile. This largely corresponds to the presence, or absence, of genes related to amino acid biosynthesis in its genome, though there are exceptions. The amino acid requirements were dramatically lost by addition of D-isomers of Met, Leu, Val, allo-Ile, Phe, Tyr, Trp and Arg. Tracer analysis using (14)C-labeled D-Trp showed that D-Trp in the medium was used as a protein component in the cells, suggesting the presence of D-amino acid metabolic enzymes. Pyridoxal 5'-phosphate (PLP)-dependent racemase activity toward Met, Leu and Phe was detected in crude extract of P. horikoshii and was enhanced in cells grown in the medium supplemented with D-amino acids, especially D-allo-Ile. The gene encoding the racemase was narrowed down to one open reading frame on the basis of enzyme purification from P. horikoshii cells, and the recombinant enzyme exhibited PLP-dependent racemase activity toward several amino acids, including Met, Leu and Phe, but not Pro, Asp or Glu. This is the first report showing the presence in a hyperthermophilic archaeon of a PLP-dependent amino acid racemase with broad substrate specificity that is likely responsible for utilization of D-amino acids for growth.

  20. Metabolic strategies of beer spoilage lactic acid bacteria in beer.

    Science.gov (United States)

    Geissler, Andreas J; Behr, Jürgen; von Kamp, Kristina; Vogel, Rudi F

    2016-01-01

    Beer contains only limited amounts of readily fermentable carbohydrates and amino acids. Beer spoilage lactic acid bacteria (LAB) have to come up with metabolic strategies in order to deal with selective nutrient content, high energy demand of hop tolerance mechanisms and a low pH. The metabolism of 26 LAB strains of 6 species and varying spoilage potentialwas investigated in order to define and compare their metabolic capabilities using multivariate statistics and outline possible metabolic strategies. Metabolic capabilities of beer spoilage LAB regarding carbohydrate and amino acids did not correlate with spoilage potential, but with fermentation type (heterofermentative/homofermentative) and species. A shift to mixed acid fermentation by homofermentative (hof) Pediococcus claussenii and Lactobacillus backii was observed as a specific feature of their growth in beer. For heterofermentative (hef) LAB a mostly versatile carbohydrate metabolism could be demonstrated, supplementing the known relevance of organic acids for their growth in beer. For hef LAB a distinct amino acid metabolism, resulting in biogenic amine production, was observed, presumably contributing to energy supply and pH homeostasis.