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Sample records for acid metabolic genes

  1. Unsaturated fatty acid: Metabolism, synthesis and gene regulation ...

    African Journals Online (AJOL)

    In both plants and animals, unsaturated fatty acids are considered to be essential membrane components. Also they play key roles in many cellular events. The synthesis and metabolism of unsaturated fatty acid are very complex processes, involving a variety of enzymes and regulated pathways. Most recently, research has ...

  2. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

    DEFF Research Database (Denmark)

    Hoeft, B.; Linseisen, J.; Beckmann, L.

    2010-01-01

    Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

  3. Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology

    Science.gov (United States)

    Sassa, Takayuki; Kihara, Akio

    2014-01-01

    Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology. PMID:24753812

  4. Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast

    Science.gov (United States)

    Misra, Ashish; Conway, Matthew F.; Johnnie, Joseph; Qureshi, Tabish M.; Lige, Bao; Derrick, Anne M.; Agbo, Eddy C.; Sriram, Ganesh

    2013-01-01

    Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound. The potent antimalarial therapeutic artemisinin and its precursors are promising candidate molecules for production in microbial hosts. Recent advances have demonstrated the production of artemisinin precursors in engineered yeast strains as an alternative to extraction from plants. We report the application of in silico and in vivo metabolic pathway analyses to identify metabolic engineering targets to improve the yield of the direct artemisinin precursor dihydroartemisinic acid (DHA) in yeast. First, in silico extreme pathway (ExPa) analysis identified NADPH-malic enzyme and the oxidative pentose phosphate pathway (PPP) as mechanisms to meet NADPH demand for DHA synthesis. Next, we compared key DHA-synthesizing ExPas to the metabolic flux distributions obtained from in vivo 13C metabolic flux analysis of a DHA-synthesizing strain. This comparison revealed that knocking out ethanol synthesis and overexpressing glucose-6-phosphate dehydrogenase in the oxidative PPP (gene YNL241C) or the NADPH-malic enzyme ME2 (YKL029C) are vital steps toward overproducing DHA. Finally, we employed in silico flux balance analysis and minimization of metabolic adjustment on a yeast genome-scale model to identify gene knockouts for improving DHA yields. The best strategy involved knockout of an oxaloacetate transporter (YKL120W) and an aspartate aminotransferase (YKL106W), and was predicted to improve DHA yields by 70-fold. Collectively, our work elucidates multiple non-trivial metabolic engineering strategies for improving DHA yield in yeast. PMID:23898325

  5. Metabolic analyses elucidate nontrivial gene targets for amplifying dihydroartemisinic acid production in yeast

    Directory of Open Access Journals (Sweden)

    Ashish eMisra

    2013-07-01

    Full Text Available Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound. The potent antimalarial therapeutic artemisinin and its precursors are promising candidate molecules for production in microbial hosts. Recent advances have demonstrated the production of artemisinin precursors in engineered yeast strains as an alternative to extraction from plants. We report the application of in silico and in vivo metabolic pathway analyses to identify metabolic engineering targets to improve the yield of the direct artemisinin precursor dihydroartemisinic acid (DHA in yeast. First, in silico extreme pathway analysis identified NADPH-malic enzyme and the oxidative pentose phosphate pathway (PPP as mechanisms to meet NADPH demand for DHA synthesis. Next, we compared key DHA-synthesizing extreme pathways to the metabolic flux distributions obtained from in vivo 13C metabolic flux analysis of a DHA-synthesizing strain. This comparison revealed that knocking out ethanol synthesis and overexpressing glucose-6-phosphate dehydrogenase in the oxidative PPP (gene YNL241C or the NADPH-malic enzyme ME2 (YKL029C are vital steps toward overproducing DHA. Finally, we employed in silico flux balance analysis and minimization of metabolic adjustment on a yeast genome-scale model to identify gene knockouts for improving DHA yields. The best strategy involved knockout of an oxaloacetate transporter (YKL120W and an aspartate aminotransferase (YKL106W, and was predicted to improve DHA yields by 70-fold. Collectively, our work elucidates multiple nontrivial metabolic engineering strategies for improving DHA yield in yeast.

  6. Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

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    Kyle J. Burghardt

    2013-01-01

    Full Text Available Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1 and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226 or bipolar disorder (n=94 were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

  7. Specificity Protein 1 Regulates Gene Expression Related to Fatty Acid Metabolism in Goat Mammary Epithelial Cells

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    Jiangjiang Zhu

    2015-01-01

    Full Text Available Specificity protein 1 (SP1 is a ubiquitous transcription factor that plays an important role in controlling gene expression. Although important in mediating the function of various hormones, the role of SP1 in regulating milk fat formation remains unknown. To investigate the sequence and expression information, as well as its role in modulating lipid metabolism, we cloned SP1 gene from mammary gland of Xinong Saanen dairy goat. The full-length cDNA of the SP1 gene is 4376 bp including 103 bp of 5'UTR, 2358 bp of ORF (HM_236311 and 1915 bp of 3'UTR, which is predicted to encode a 786 amino acids polypeptide. Phylogenetic tree analysis showed that goat SP1 has the closest relationship with sheep, followed by bovines (bos taurus, odobenus and ceratotherium, pig, primates (pongo, gorilla, macaca and papio and murine (rattus and mus, while the furthest relationship was with canis and otolemur. Expression was predominant in the lungs, small intestine, muscle, spleen, mammary gland and subcutaneous fat. There were no significant expression level differences between the mammary gland tissues collected at lactation and dry-off period. Overexpression of SP1 in goat mammary epithelial cells (GMECs led to higher mRNA expression level of peroxisome proliferator-activated receptor-γ (PPARγ and lower liver X receptor α (LXRα mRNA level, both of which were crucial in regulating fatty acid metabolism, and correspondingly altered the expression of their downstream genes in GMECs. These results were further enhanced by the silencing of SP1. These findings suggest that SP1 may play an important role in fatty acid metabolism.

  8. Effect of Polyunsaturated Fatty Acids on Homocysteine Metabolism through Regulating the Gene Expressions Involved in Methionine Metabolism

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    Tao Huang

    2013-01-01

    Full Text Available The objective was to investigate the regulatory effect of polyunsaturated fatty acids (PUFAs on mRNA expression of key genes involved in homocysteine (Hcy metabolism. Eighty male Sprague Dawley rats were randomly divided into eight groups. The oils were orally administered daily for 8 weeks. Plasma Hcy, phospholipids fatty acids, and mRNA expression were determined. Compared with the control group, plasma Hcy was significantly decreased in the 22:6n-3 and conjugated linoleic acid (CLA groups; mRNA expression of Mthfr was significantly upregulated in the 22:6n-3, 20:5n-3, and 18:3n-3 groups and downregulated in the 18:2n-6 and stearolic acid (SO groups. Mat1a was upregulated in the 22:6n-3, 20:5n-3, 18:3n-3, and CLA groups. In addition, Cbs was upregulated in the 22:6n-3, 20:5n-3, 18:3n-3 and CLA groups while downregulated in 18:2n-6 and SO groups. Dietary 22:6n-3 and CLA decrease the plasma concentration of Hcy. mRNA expression of Mthfr, Mat1a, Cbs and Pemt, Gnmt, Mtrr, and Bad is upregulated by n-3 PUFA and downregulated by n-6 PUFA. CLA upregulates mRNA expression of Mat1a and Cbs.

  9. Metabolic gene-targeted monitoring of non-starter lactic acid bacteria during cheese ripening.

    Science.gov (United States)

    Levante, Alessia; De Filippis, Francesca; La Storia, Antonietta; Gatti, Monica; Neviani, Erasmo; Ercolini, Danilo; Lazzi, Camilla

    2017-09-18

    Long ripened cheeses, such as Grana Padano (GP), a Protected Designation of Origin (PDO) Italian cheese, harbor a viable microbiota mainly composed of non-starter lactic acid bacteria (NSLAB), which contribute to the final characteristics of cheese. The NSLAB species Lactobacillus rhamnosus, Lb. casei and Lb. paracasei are frequently found in GP, and form a closely related taxonomic group (Lb. casei group), making it difficult to distinguish the three species through 16S rRNA sequencing. SpxB, a metabolic gene coding for pyruvate oxidase in Lb. casei group, was recently used to distinguish the species within this bacterial group, both in pure cultures and in cheese, where it could provide an alternative energy source through the conversion of pyruvate to acetate. The aim of this work was to study the evolution of the metabolically active microbiota during different stages of GP ripening, targeting 16S rRNA to describe the whole microbiota composition, and spxB gene to monitor the biodiversity within the Lb. casei group. Furthermore, activation of pyruvate oxidase pathway was measured directly in cheese by reverse transcription real time PCR (RT-qPCR). The results showed that Lb. casei group dominates throughout the ripening and high-throughput sequencing of spxB allowed to identify four clusters inside the Lb. casei group. The dynamics of the sequence types forming the clusters were followed during ripening. Pyruvate oxidase pathway was expressed in cheese, showing a decreasing trend over ripening time. This work highlights how the composition of the microbiota in the early manufacturing stages influences the microbial dynamics throughout ripening, and how targeting of a metabolic gene can provide an insight into the activity of strains relevant for dairy products. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Systematic identification of genes involved in metabolic acid stress resistance in yeast and their potential as cancer targets

    Directory of Open Access Journals (Sweden)

    John J. Shin

    2016-09-01

    Full Text Available A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We identified six highly conserved protein complexes with functions related to oxidative phosphorylation (mitochondrial respiratory chain complex III and IV, mitochondrial tRNA biosynthesis [glutamyl-tRNA(Gln amidotransferase complex], histone methylation (Set1C–COMPASS, lysosome biogenesis (AP-3 adapter complex, and mRNA processing and P-body formation (PAN complex. We tested roles for two of these, AP-3 adapter complex and PAN deadenylase complex, in resistance to acid stress using a myeloid leukaemia-derived human cell line that we determined to be acid stress resistant. Loss of either complex inhibited growth of Hap1 cells at neutral pH and caused sensitivity to acid stress, indicating that AP-3 and PAN complexes are promising new targets in the treatment of cancer. Additionally, our data suggests that tumours may be genetically sensitized to acid stress and hence susceptible to acid stress-directed therapies, as many tumours accumulate mutations in mitochondrial

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

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    Sofía Arriarán

    2015-11-01

    Full Text Available 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.

  12. Improved Acetic Acid Resistance in Saccharomyces cerevisiae by Overexpression of the WHI2 Gene Identified through Inverse Metabolic Engineering

    OpenAIRE

    Chen, Yingying; Stabryla, Lisa; Wei, Na

    2016-01-01

    Development of acetic acid-resistant Saccharomyces cerevisiae is important for economically viable production of biofuels from lignocellulosic biomass, but the goal remains a critical challenge due to limited information on effective genetic perturbation targets for improving acetic acid resistance in the yeast. This study employed a genomic-library-based inverse metabolic engineering approach to successfully identify a novel gene target, WHI2 (encoding a cytoplasmatic globular scaffold prote...

  13. Improved Acetic Acid Resistance in Saccharomyces cerevisiae by Overexpression of the WHI2 Gene Identified through Inverse Metabolic Engineering

    Science.gov (United States)

    Chen, Yingying; Stabryla, Lisa

    2016-01-01

    Development of acetic acid-resistant Saccharomyces cerevisiae is important for economically viable production of biofuels from lignocellulosic biomass, but the goal remains a critical challenge due to limited information on effective genetic perturbation targets for improving acetic acid resistance in the yeast. This study employed a genomic-library-based inverse metabolic engineering approach to successfully identify a novel gene target, WHI2 (encoding a cytoplasmatic globular scaffold protein), which elicited improved acetic acid resistance in S. cerevisiae. Overexpression of WHI2 significantly improved glucose and/or xylose fermentation under acetic acid stress in engineered yeast. The WHI2-overexpressing strain had 5-times-higher specific ethanol productivity than the control in glucose fermentation with acetic acid. Analysis of the expression of WHI2 gene products (including protein and transcript) determined that acetic acid induced endogenous expression of Whi2 in S. cerevisiae. Meanwhile, the whi2Δ mutant strain had substantially higher susceptibility to acetic acid than the wild type, suggesting the important role of Whi2 in the acetic acid response in S. cerevisiae. Additionally, overexpression of WHI2 and of a cognate phosphatase gene, PSR1, had a synergistic effect in improving acetic acid resistance, suggesting that Whi2 might function in combination with Psr1 to elicit the acetic acid resistance mechanism. These results improve our understanding of the yeast response to acetic acid stress and provide a new strategy to breed acetic acid-resistant yeast strains for renewable biofuel production. PMID:26826231

  14. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

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    Siegmund Kimberly D

    2010-10-01

    Full Text Available Abstract Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

  15. Effect of Diet Supplementation on the Expression of Bovine Genes Associated with Fatty Acid Synthesis and Metabolism

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    Sandeep J. Joseph

    2010-03-01

    Full Text Available Conjugated linoleic acids (CLA are of important nutritional and health benefit to human. Food products of animal origin are their major dietary source and their concentration increases with high concentrate diets fed to animals. To examine the effects of diet supplementation on the expression of genes related to lipid metabolism, 28 Angus steers were fed either pasture only, pasture with soybean hulls and corn oil, pasture with corn grain, or high concentrate diet. At slaughter, samples of subcutaneous adipose tissue were collected, from which RNA was extracted. Relative abundance of gene expression was measured using Affymetrix GeneChip Bovine Genome array. An ANOVA model nested within gene was used to analyze the background adjusted, normalized average difference of probe-level intensities. To control experiment wise error, a false discovery rate of 0.01 was imposed on all contrasts. Expression of several genes involved in the synthesis of enzymes related to fatty acid metabolism and lipogenesis such as stearoyl-CoA desaturase (SCD, fatty acid synthetase (FASN, lipoprotein lipase (LPL, fatty-acyl elongase (LCE along with several trancription factors and co-activators involved in lipogenesis were found to be differentially expressed. Confirmatory RT-qPCR was done to validate the microarray results, which showed satisfactory correspondence between the two platforms. Results show that changes in diet by increasing dietary energy intake by supplementing high concentrate diet have effects on the transcription of genes encoding enzymes involved in fat metabolism which in turn has effects on fatty acid content in the carcass tissue as well as carcass quality. Corn supplementation either as oil or grain appeared to significantly alter the expression of genes directly associated with fatty acid synthesis.

  16. Atorvastatin alters the expression of genes related to bile acid metabolism and circadian clock in livers of mice

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    Wen-Kai Li

    2017-05-01

    Full Text Available Aim Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. Methods Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined. Results Repeated administration of atorvastatin did not affect animal body weight gain or liver weights. Serum enzyme activities were in the normal range. Histologically, the high dose of atorvastatin produced scattered swollen hepatocytes, foci of feathery-like degeneration, together with increased expression of Egr-1 and metallothionein-1. Atorvastatin increased the expression of Cyp7a1 in the liver, along with FXR and SHP. In contract, atorvastatin decreased the expression of bile acid transporters Ntcp, Bsep, Ostα, and Ostβ. The most dramatic change was the 30-fold induction of Cyp7a1. Because Cyp7a1 is a circadian clock-controlled gene, we further examined the effect of atorvastatin on clock gene expression. Atorvastatin increased the expression of clock core master genes Bmal1 and Npas2, decreased the expression of clock feedback genes Per2, Per3, and the clock targeted genes Dbp and Tef, whereas it had no effect on Cry1 and Nr1d1 expression. Conclusion Repeated administration of atorvastatin affects bile acid metabolism and markedly increases the expression of the bile acid synthesis rate-limiting enzyme gene Cyp7a1, together with alterations in the expression of circadian clock genes.

  17. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  18. Expression of Shewanella frigidimarina fatty acid metabolic genes in E. coli by CRISPR/cas9-coupled lambda Red recombineering.

    Science.gov (United States)

    Xia, Jun; Wang, Ling; Zhu, Jian-bo; Sun, Cheng-jun; Zheng, Ming-gang; Zheng, Li; Lou, Ying-hua; Shi, Lei

    2016-01-01

    To construct a clustered, regularly interspaced, short palindromic repeats (CRISPR)/cas9 system and use this system to obtain a recombinant Escherichia coli strain possessing the fatty acid metabolism genes from a lipid-rich marine bacterium. The fatty acid regulatory transcription factor (fadR), delta9 (Δ(9) desaturase) and acetyl-CoA carboxylase (acc) genes were cloned from Shewanella frigidimarina. The fatty acid regulatory transcription factor (fadD) and phosphoenolpyruvate carboxylase inactivated strains were used to construct the fadR/delta9 and acc knock-in strains, which are both markerless and "scar"-less, and identified the change in fatty acid composition in the recombinant strains. There was no change in fatty acid composition between the wild-type strain and recombinant strains. All strains had 11:0, 12:0, 13:0, 14:0, 15:0, 16:0, 17:1, 17:0 and 18:0 fatty acids, with 16:0 and 18:0 fatty acids being dominant. The total lipid content of each recombinant strain was higher than the wild-type strain, with a maximum of 13.1 %, nearly 5.3 % higher than wild-type strain. The CRISPR/cas9 system, in conjunction with λ-Red recombinases, can rapidly and efficiently edit the E. coli genome. The CRISPR/cas9 recombineering machinery can be modified to select biotechnologically-relevant bacteria other than E. coli.

  19. Effect of Non-Esterified Fatty Acids on Fatty Acid Metabolism-Related Genes in Calf Hepatocytes Cultured in Vitro

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    Peng Li

    2013-11-01

    Full Text Available Background: NEFA plays numerous roles in the metabolism of glucose, lipids, and proteins. A number of experimental studies have shown that NEFA may have an important role in fatty acid metabolism in the liver, especially in dairy cows that experience negative energy balance (NEB during early lactation. Methods: In this study, using fluorescent quantitative RT-PCR, ELISA, and primary hepatocytes cultured in vitro, we examined the effect of NEFA (0, 0.2, 0.4, 0.8, 1.6, and 3.2 mmol/L on fatty acid metabolism by monitoring the mRNA and protein expression of the following key enzymes: long chain acyl-CoA synthetase (ACSL, carnitine palmitoyltransferase IA (CPT IA, long chain acyl-CoA dehydrogenase (ACADL, and acetyl-CoA carboxylase (ACC. Results: The mRNA and protein expression levels of ACSL and ACADL markedly increased as the concentration of NEFA in the media was increased. The mRNA and protein expression levels of CPT IA were enhanced significantly when the NEFA concentrations increased from 0 to 1.6 mmol/L and decreased significantly when the NEFA concentrations increased from 1.6 to 3.2 mmol/L. The mRNA and protein expression of ACC decreased gradually with increasing concentrations of NEFA. Conclusion: These findings indicate that increased NEFA significantly promote the activation and β-oxidation of fatty acids, but very high NEFA concentrations may inhibit the translocation of fatty acids into mitochondria of hepatocytes. This may explain the development of ketosis or liver lipidosis in dairy cows. CPT IA might be the key control enzyme of the fatty acid oxidation process in hepatocytes.

  20. Sialic acid metabolism is involved in the regulation of gene expression during neuronal differentiation of PC12 cells.

    Science.gov (United States)

    Kontou, Maria; Bauer, Christian; Reutter, Werner; Horstkorte, Rüdiger

    2008-04-01

    Sialic acid precursors are mediators of the sialic acid pathway. In this manuscript we present evidence that the application of sialic acid a precursor modulates gene expression and cell differentiation. The concept that sugars are involved in cellular transcription was first proposed by Jacob and Monod nearly 40 years ago studying the regulation of the lac-operon in prokaryotes. Surprisingly, these findings have never been transferred to eukaryotic systems. For our studies we have chosen PC12 cells. PC12-cells differentiate after application of NGF into a neuron-like phenotype. It is shown that treatment of PC12 cells with two different sialic acid precursors N-acetyl- or N-propanoylmannosamine, without application of NGF also induces neurite outgrowth. Moreover, the PC12 cells show the same morphology as the NGF-treated cells. Surprisingly, after application of both sialic acid precursors the phosphorylation and translocation of erk1/2 into the nucleus are activated, thus influencing the expression of genes involved in the differentiation of cells, such as the transcription factor c-Jun or TOAD-64/Ulip/CRMP (Turned ON After Division, 64 kd/ unc-33-like phosphoprotein/Collapsin Response Mediator Protein). These are the first experimental data showing that the sialic acid metabolism is closely associated with signal transduction and regulation of neuronal differentiation.

  1. (-)-Hydroxycitric acid reduced fat deposition via regulating lipid metabolism-related gene expression in broiler chickens.

    Science.gov (United States)

    Han, Jing; Li, Longlong; Wang, Dian; Ma, Haitian

    2016-02-24

    Chicken as a delicious food for a long history, and it is well known that excess fat deposition in broiler chickens will not only induced metabolic diseases, but also lead to adverse effect in the consumer's health. (-)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress fat accumulation in animals and humans. While, the precise physiological mechanism of HCA has not yet been full clarified, especially its action in broiler chickens. Thus, this study aimed to assess the effect of (-)-HCA on lipid metabolism in broiler chickens. A total of 120 1-day-old broiler chickens were randomly allocated to four groups, with each group was repeated three times with 10 birds. Birds received a commercial diet supplemented with (-)-HCA at 0, 1000, 2000 or 3000 mg/kg, respectively, for a period of 4 weeks ad libitum. Body weight (BW) in the 2000 and 3000 mg/kg (-)-HCA groups was significantly decreased (P Broiler chickens supplmented with 2000 and 3000 mg/kg (-)-HCA had pronouncedly higher hepatic lipase (HL) activity, hepatic glycogen and non-esterified fatty acid (NEFA) contents in liver (P broiler chickens supplemented with 3000 mg/kg (-)-HCA. No differences was observed on carnitine palmitoyl transferase-I(CPT-I), while peroxisome proliferators-activated receptor α (PPARα) mRNA level (P broiler chickens supplemented with 2000 and 3000 mg/kg (-)-HCA. Supplemental (-)-HCA inhibited lipogenesis by inhibiting ACLY, SREBP-1c and FAS expression, and accelerated lipolysis through enhancing HL activity and PPARα expression, which eventually led to the reduced abdominal fat deposition in broiler chickens. Graphical abstract Mechanism of (-)-HCA effect on hepatic lipids metabolism.

  2. Effect of common single-nucleotide polymorphisms in acetylsalicylic acid metabolic pathway genes on platelet reactivity in patients with diabetes

    Science.gov (United States)

    Postula, Marek; Janicki, Piotr K.; Rosiak, Marek; Kaplon-Cieslicka, Agnieszka; Kondracka, Agnieszka; Trzepla, Ewa; Filipiak, Krzysztof J.; Kosior, Dariusz A.; Czlonkowski, Andrzej; Opolski, Grzegorz

    2013-01-01

    Background Platelet reactivity in patients on acetylsalicylic acid (ASA) therapy can be influenced by physiological or pathological conditions affecting ASA pharmacokinetics or pharmacodynamics. The mechanism of such variability in the therapeutic response to ASA, particularly in diabetic patients, is poorly understood. The rate of elimination of ASA and its metabolite, salicylic acid (SA), is likely a major factor determining drug efficacy. The objective of this study was to investigate the effect of genetic polymorphisms in the selected candidate genes within the ASA metabolic pathway on the platelet reactivity and concentration of ASA and thromboxane A2 (TxA2) metabolites in a population of patients with type 2 diabetes mellitus (T2DM). Material/Methods The study cohort consisted of 287 Caucasians with T2DM who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months. Platelet reactivity analyses were performed using VerifyNow Aspirin and PFA-100 assays. The measured ASA metabolite included salicylic acid (ASA), and TxA2 metabolites included serum TxB2 and urinary 11-dh-TxB2. Genotyping for the selected 18 single-nucleotide polymorphisms (SNPs) within 5 genes of the ASA metabolic pathway was performed using a Sequenom iPLEX platform. Results No statistically significant association was observed between the investigated SNPs genotypes, platelet reactivity, and measured metabolites in the investigated cohort of patients. Conclusions The results of our study failed to confirm that the selected variants in the genes within the ASA metabolic pathway might contribute to platelet reactivity in a diabetic population treated with ASA. PMID:23715170

  3. Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism.

    Science.gov (United States)

    Oehler, Nicola; Volz, Tassilo; Bhadra, Oliver D; Kah, Janine; Allweiss, Lena; Giersch, Katja; Bierwolf, Jeanette; Riecken, Kristoffer; Pollok, Jörg M; Lohse, Ansgar W; Fehse, Boris; Petersen, Joerg; Urban, Stephan; Lütgehetmann, Marc; Heeren, Joerg; Dandri, Maura

    2014-11-01

    Chronic hepatitis B virus (HBV) infection has been associated with alterations in lipid metabolism. Moreover, the Na+-taurocholate cotransporting polypeptide (NTCP), responsible for bile acid (BA) uptake into hepatocytes, was identified as the functional cellular receptor mediating HBV entry. The aim of the study was to determine whether HBV alters the liver metabolic profile by employing HBV-infected and uninfected human liver chimeric mice. Humanized urokinase plasminogen activator/severe combined immunodeficiency mice were used to establish chronic HBV infection. Gene expression profiles were determined by real-time polymerase chain reaction using primers specifically recognizing transcripts of either human or murine origin. Liver biopsy samples obtained from HBV-chronic individuals were used to validate changes determined in mice. Besides modest changes in lipid metabolism, HBV-infected mice displayed a significant enhancement of human cholesterol 7α-hydroxylase (human [h]CYP7A1; median 12-fold induction; Pmetabolic alterations. Binding of HBV to NTCP limits its function, thus promoting compensatory BA synthesis and cholesterol provision. The intimate link determined between HBV and liver metabolism underlines the importance to exploit further metabolic pathways, as well as possible NTCP-related viral-drug interactions. © 2014 by the American Association for the Study of Liver Diseases.

  4. Effect of α-linolenic acid and DHA intake on lipogenesis and gene expression involved in fatty acid metabolism in growing-finishing pigs.

    Science.gov (United States)

    De Tonnac, A; Labussière, E; Vincent, A; Mourot, J

    2016-07-01

    The regulation of lipogenesis mechanisms related to consumption of n-3 PUFA is poorly understood. The aim of the present study was to find out whether α-linolenic acid (ALA) or DHA uptake can have an effect on activities and gene expressions of enzymes involved in lipid metabolism in the liver, subcutaneous adipose tissue and longissimus dorsi (LD) muscle of growing-finishing pigs. Six groups of ten pigs received one of six experimental diets supplemented with rapeseed oil in the control diet, extruded linseed, microalgae or a mixture of both to implement different levels of ALA and DHA with the same content in total n-3. Results were analysed for linear and quadratic effects of DHA intake. The results showed that activities of malic enzyme (ME) and fatty acid synthase (FAS) decreased linearly in the liver with dietary DHA. Although the expression of the genes of these enzymes and their activities were poorly correlated, ME and FAS expressions also decreased linearly with DHA intake. The intake of DHA down-regulates the expressions of other genes involved in fatty acid (FA) metabolism in some tissues of pigs, such as fatty acid desaturase 2 and sterol-regulatory element binding transcription factor 1 in the liver and 2,4-dienoyl CoA reductase 2 in the LD muscle. FA oxidation in the LD muscle and FA synthesis decreased in the liver with increasing amount of dietary DHA, whereas a retroconversion of DHA into EPA seems to be set up in this last tissue.

  5. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  6. An Association Study Between Gene Polymorphisms of Folic Acid Metabolism Enzymes and Biochemical and Hormonal Parameters in Acromegaly.

    Science.gov (United States)

    Tetik Vardarlı, Aslı; Zengi, Ayhan; Bozok Çetintaş, Vildan; Karadeniz, Muammer; Tamsel, Sadık; Küçükaslan, Ali Şahin; Köse, Timur; Saygılı, Füsun; Eroglu, Zuhal

    2015-08-01

    Folate metabolism is fundamental to several biological functions and required for cell replication, division, and survival. The mammalian folic acid cycle is highly complex and the enzymes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR), have crucial roles in this metabolic pathway. The common polymorphisms of the MTHFR (C677T and A1298C), MTRR (A66G), and MTR (A2756G) enzymes are well documented as folate deficiency-related disorders, but their roles have not been examined in acromegalic patients. The aim of this study was to compare the genotypic distribution of these gene polymorphisms between patients with acromegaly and controls and explore whether these polymorphisms were associated with biochemical and hormonal parameters in acromegaly. We examined 91 acromegaly patients and 112 healthy subjects who were compared in terms of age and gender. Blood specimens of the subjects were collected in tubes containing ethylenediaminetetraacetic acid. Genomic DNA was isolated from peripheral blood leukocytes and genotyping of the MTHFR (C677T and A1298C) gene polymorphisms was assessed by melting temperature analyses after real-time polymerase chain reaction (PCR), whereas MTRR A66G and MTR A2756G gene polymorphism analyses were performed by PCR/restriction fragment length polymorphism from the isolated DNA of the subjects. MTHFR-677TT genotype frequency was significantly higher in the acromegaly group than the control group (p=0.017), and a significant increase was found in fibrinogen (p=0.032) levels in 677TT-carrying acromegaly patients. MTRR-66AA genotype was significantly higher in the control group than the acromegaly group (p=0.004). Total cholesterol (p=0.048) and C-reactive protein (p=0.046) levels decreased significantly in 66AA genotypes. Although MTR-2756AG genotype frequency was not different between the control and acromegaly groups, 2756AG genotype-carrying individuals have higher left

  7. Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis

    Directory of Open Access Journals (Sweden)

    Braunstein Evan M

    2009-05-01

    Full Text Available Abstract Background In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. Tbx1, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. Tbx1 is expressed in the otic epithelium and adjacent periotic mesenchyme (POM, and both of these domains are required for inner ear formation. To study the function of Tbx1 in the POM, we have conditionally inactivated Tbx1 in the mesoderm while keeping expression in the otic vesicle intact. Results Conditional mutants (TCre-KO displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that Tbx1 expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker Brn4 was also lost in the TCre-KO. Brn4-;Tbx1+/-embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA catabolizing genes was examined in both mutants. Cyp26a1 expression was altered in the TCre-KO, while Cyp26c1 showed reduced expression in both TCre-KO and Brn4-;Tbx1+/- embryos. Conclusion These results indicate that Tbx1 expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.

  8. Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

    Science.gov (United States)

    Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

    2015-02-01

    Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

  9. G109T polymorphism of SLC22A12 gene is associated with serum uric acid level, but not with metabolic syndrome.

    Science.gov (United States)

    Jang, Won Cheoul; Nam, Youn Hyoung; Ahn, Young Chang; Park, Su Min; Yoon, Il Kyu; Choe, Jung-Yoon; Park, Sung-Hoon; Her, Minyoung; Kim, Seong-Kyu

    2012-08-01

    SLC22A12 gene, encoding urate transport 1, has been known to be responsible to urate metabolism. This study sought to determine the association between the novel G109T polymorphism in SLC22A12 with serum uric acid and the development of metabolic syndrome in Korean male subjects. A total of 132 healthy male subjects were enrolled in this study. Metabolic syndrome was determined using the modified guidelines for metabolic syndrome proposed by the National Cholesterol Education Program's Third Adult Treatment Panel. Genotyping for the SLC22A12 gene was assessed using denaturing high-performance liquid chromatography analysis. Serum uric acid and fractional excretion of uric acid (FEUA) from blood and urine samples were measured. Frequencies of the 109GG, 109GT, and 109TT genotypes were 57.6, 38.6, and 3.8%, respectively. Serum uric acid levels and FEUAs were significantly different among the three genotypes of the G109T polymorphism (P = 0.035 and P = 0.033, respectively). In addition, subjects of genotypes with the T allele had lower uric acid levels and higher FEUAs compared to those with the 109GG genotype (P = 0.007 and P = 0.031, respectively). The G109T polymorphism of the SLC22A12 gene has no association with metabolic syndrome. However, a number of metabolic syndrome components were related to serum uric acid level (r = 0.285, P = 0.001) and also significantly different between genotype with and without T allele (P = 0.008). The novel G109T polymorphism of the SLC22A12 gene is related to serum uric acid level, but not to the development of metabolic syndrome.

  10. Retinoic acid metabolic genes, meiosis, and gonadal sex differentiation in zebrafish.

    Directory of Open Access Journals (Sweden)

    Adriana Rodríguez-Marí

    Full Text Available To help understand the elusive mechanisms of zebrafish sex determination, we studied the genetic machinery regulating production and breakdown of retinoic acid (RA during the onset of meiosis in gonadogenesis. Results uncovered unexpected mechanistic differences between zebrafish and mammals. Conserved synteny and expression analyses revealed that cyp26a1 in zebrafish and its paralog Cyp26b1 in tetrapods independently became the primary genes encoding enzymes available for gonadal RA-degradation, showing lineage-specific subfunctionalization of vertebrate genome duplication (VGD paralogs. Experiments showed that zebrafish express aldh1a2, which encodes an RA-synthesizing enzyme, in the gonad rather than in the mesonephros as in mouse. Germ cells in bipotential gonads of all zebrafish analyzed were labeled by the early meiotic marker sycp3, suggesting that in zebrafish, the onset of meiosis is not sexually dimorphic as it is in mouse and is independent of Stra8, which is required in mouse but was lost in teleosts. Analysis of dead-end knockdown zebrafish depleted of germ cells revealed the germ cell-independent onset and maintenance of gonadal aldh1a2 and cyp26a1 expression. After meiosis initiated, somatic cell expression of cyp26a1 became sexually dimorphic: up-regulated in testes but not ovaries. Meiotic germ cells expressing the synaptonemal complex gene sycp3 occupied islands of somatic cells that lacked cyp26a1 expression, as predicted by the hypothesis that Cyp26a1 acts as a meiosis-inhibiting factor. Consistent with this hypothesis, females up-regulated cyp26a1 in oocytes that entered prophase-I meiotic arrest, and down-regulated cyp26a1 in oocytes resuming meiosis. Co-expression of cyp26a1 and the pluripotent germ cell stem cell marker pou5f1(oct4 in meiotically arrested oocytes was consistent with roles in mouse to promote germ cell survival and to prevent apoptosis, mechanisms that are central for tipping the sexual fate of gonads

  11. Dietary fat source affects metabolism of fatty acids in pigs as evaluated by altered expression of lipogenic genes in liver and adipose tissues

    DEFF Research Database (Denmark)

    Duran-Montge, P; Theil, Peter Kappel; Lauridsen, Charlotte

    2009-01-01

    Little is known about pig gene expressions related to dietary fatty acids (FAs) and most work have been conducted in rodents. The aim of this study was to investigate how dietary fats regulate fat metabolism of pigs in different tissues. Fifty-six crossbred gilts (62 ± 5.2 kg BW) were fed one of ...

  12. Crassulacean acid metabolism

    Directory of Open Access Journals (Sweden)

    Thomas David Geydan

    2005-07-01

    Full Text Available A review of Crassulacean acid metabolism is presented, characterized by showing the occurrence, activity and plasticity of these complex mechanism at the physiological, biochemical and molecular level, framed by the presence of the denominated four phases in CAM and its repercussion and expression due to different stresses in an ecological context. The basic enzymes, and metabolites necessary for the optional functioning of CAM are presented as well as their mode of action and cellular control. Finally, it is shown how environmental conditions and molecular signalling mediate the phenotypic plasticity.

  13. Polymorphism rs1761667 in the CD36 Gene Is Associated to Changes in Fatty Acid Metabolism and Circulating Endocannabinoid Levels Distinctively in Normal Weight and Obese Subjects

    Directory of Open Access Journals (Sweden)

    Melania Melis

    2017-12-01

    Full Text Available The multifunctional CD36 scavenger receptor facilitates fatty acid (FA uptake and oxidation and it has been involved in the pathophysiology related to dysfunctional FA metabolism. The common variant in the CD36 gene, rs1761667 (A/G, whose allele A is characterized by a reduced protein expression, has been associated with taste sensitivity to and preference for fat. We therefore aimed at evaluating whether the CD36 polymorphism may influence fatty acid metabolism and endocannabinoid biosynthesis in normal weight (NW and obese (OB subjects. Red blood cell (RBC fatty acid composition, and plasma endocannabinoid levels were determined. In NW subjects with AA genotype was found a marked reduction of RBC saturated fatty acids and palmitic/linoleic ratio (PA/LA, considered as de novo lipogenesis (DNL biomarkers. Remarkably, to the reduction of DNL biomarkers corresponded an increase of omega-6 index, an indirect marker of the impact on fatty acid metabolism of dietary omega-6 fatty acids, endocannabinoid levels and a higher waist/hip ratio. The presence of the G allele was instead associated with increased endocannabinoid plasma levels and a trend for increased waist/hip ratio in obese subjects, even though exhibited decreased BMI with respect to those with AA genotype. These data indicate that the CD36 polymorphism, rs1761667, leads to a distinct metabolic pattern in NW and in OB subjects. Therefore, their determination may be crucial in developing personalized therapeutic strategies for ameliorating dyslipidemia and other metabolic disorders.

  14. Analysis of cytokinin mutants and regulation of cytokinin metabolic genes reveals important regulatory roles of cytokinins in drought, salt and abscisic acid responses, and abscisic acid biosynthesis.

    Science.gov (United States)

    Nishiyama, Rie; Watanabe, Yasuko; Fujita, Yasunari; Le, Dung Tien; Kojima, Mikiko; Werner, Tomás; Vankova, Radomira; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo; Kakimoto, Tatsuo; Sakakibara, Hitoshi; Schmülling, Thomas; Tran, Lam-Son Phan

    2011-06-01

    Cytokinins (CKs) regulate plant growth and development via a complex network of CK signaling. Here, we perform functional analyses with CK-deficient plants to provide direct evidence that CKs negatively regulate salt and drought stress signaling. All CK-deficient plants with reduced levels of various CKs exhibited a strong stress-tolerant phenotype that was associated with increased cell membrane integrity and abscisic acid (ABA) hypersensitivity rather than stomatal density and ABA-mediated stomatal closure. Expression of the Arabidopsis thaliana ISOPENTENYL-TRANSFERASE genes involved in the biosynthesis of bioactive CKs and the majority of the Arabidopsis CYTOKININ OXIDASES/DEHYDROGENASES genes was repressed by stress and ABA treatments, leading to a decrease in biologically active CK contents. These results demonstrate a novel mechanism for survival under abiotic stress conditions via the homeostatic regulation of steady state CK levels. Additionally, under normal conditions, although CK deficiency increased the sensitivity of plants to exogenous ABA, it caused a downregulation of key ABA biosynthetic genes, leading to a significant reduction in endogenous ABA levels in CK-deficient plants relative to the wild type. Taken together, this study provides direct evidence that mutual regulation mechanisms exist between the CK and ABA metabolism and signals underlying different processes regulating plant adaptation to stressors as well as plant growth and development.

  15. Effect of fulvic acid induction on the physiology, metabolism, and lipid biosynthesis-related gene transcription of Monoraphidium sp. FXY-10.

    Science.gov (United States)

    Che, Raoqiong; Huang, Li; Xu, Jun-Wei; Zhao, Peng; Li, Tao; Ma, Huixian; Yu, Xuya

    2017-03-01

    Fulvic acid (FA) triggers lipid accumulation in Monoraphidium sp. FXY-10, which can produce biofuels. Therefore, the metabolism shift and gene expression changes influenced by fulvic acid should be investigated. In this study, lipid and protein contents increased rapidly from 44.6% to 54.3% and from 31.4% to 39.7% under FA treatment, respectively. By contrast, carbohydrate content sharply declined from 49.5% to 32.5%. The correlation between lipid content and gene expression was also analyzed. Results revealed that accD, ME, and GPAT genes were significantly correlated with lipid accumulation. These genes could likely influence lipid accumulation and could be selected as modification candidates. These results demonstrated that FA significantly increased microalgal lipid accumulation by changing the intracellular reactive oxygen species, gene expression, and enzyme activities of acetyl-CoA carboxylase, malic enzyme, and phosphoenolpyruvate carboxylase. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat

    Science.gov (United States)

    We determined effects of soy protein (SPI) and the isoflavone genistein (GEN) on mRNA expression of key lipid metabolism and thyroid hormone system genes in young adult, male Sprague-Dawley rats. SPI-fed rats had less retroperitoneal fat and less hepato-steatosis than casein (CAS, control protein)-...

  17. Role of exercise-induced calmodulin protein kinase (CAMK)II activation in the regulation of omega-6 fatty acids and lipid metabolism genes in rat skeletal muscle.

    Science.gov (United States)

    Joseph, J S; Ayeleso, A O; Mukwevho, E

    2017-09-22

    Activation of calmodulin dependent protein kinase (CaMK)II by exercise is beneficial in controlling membrane lipids associated with type 2 diabetes and obesity. Regulation of lipid metabolism is crucial in the improvement of type 2 diabetes and obesity associated symptoms. The role of CaMKII in membrane associated lipid metabolism was the focus of this study. Five to six weeks old male Wistar rats were used in this study. GC×GC-TOFMS technique was used to determine the levels of polyunsaturated fatty acids (linoleic acid, arachidonic acid and 11,14-eicosadienoic acid). Carnitine palmitoyltransferase (Cpt-1) and acetyl-CoA carboxylase (Acc-1) genes expression were assessed using quantitative real time PCR (qPCR). From the results, CaMKII activation by exercise increased the levels of arachidonic acid and 11, 14-eicosadienoic acid while a decrease in the level of linolenic acid was observed in the skeletal muscle. The results indicated that exercise-induced CaMKII activation increased CPT-1 expression and decreased ACC-1 expression in rat skeletal muscle. All the observed increases with activation of CaMKII by exercise were aborted when KN93, an inhibitor of CaMKII was injected in exercising rats. This study demonstrated that CaMKII activation by exercise regulated lipid metabolism. This study suggests that CaMKII can be a vital target of therapeutic approach in the management of diseases such as type 2 diabetes and obesity that have increased to epidemic proportions recently.

  18. A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

    Science.gov (United States)

    Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

    2017-07-01

    Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

  19. Grr1p is required for transcriptional induction of amino acid permease genes and proper transcriptional regulation of genes in carbon metabolism of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Regenberg, Birgitte; Nielsen, Jens

    2005-01-01

    The F-box protein Grr1p is involved in cell cycle regulation, glucose repression and transcriptional induction of the amino acid permease (AAP) gene AGP1. We investigated the role of Grr1p in amino acid-mediated induction of AAP genes by performing batch cultivations with a wild-type strain and a...

  20. MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries

    Directory of Open Access Journals (Sweden)

    Svetlana Uzbekova

    2015-03-01

    Full Text Available In mammals, oocytes develop inside the ovarian follicles; this process is strongly supported by the surrounding follicular environment consisting of cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle, the final stages of oogenesis require large amounts of energy that is produced by follicular cells from substrates including glucose, amino acids and fatty acids (FAs. Since lipid metabolism plays an important role in acquiring oocyte developmental competence, the aim of this study was to investigate site-specificity of lipid metabolism in ovaries by comparing lipid profiles and expression of FA metabolism-related genes in different ovarian compartments. Using MALDI Mass Spectrometry Imaging, images of porcine ovary sections were reconstructed from lipid ion signals for the first time. Cluster analysis of ion spectra revealed differences in spatial distribution of lipid species among ovarian compartments, notably between the follicles and interstitial tissue. Inside the follicles analysis differentiated follicular fluid, granulosa, theca and the oocyte-cumulus complex. Moreover, by transcript quantification using real time PCR, we showed that expression of five key genes in FA metabolism significantly varied between somatic follicular cells (theca, granulosa and cumulus and the oocyte. In conclusion, lipid metabolism differs between ovarian and follicular compartments.

  1. Conserved and Divergent Rhythms of Crassulacean Acid Metabolism-Related and Core Clock Gene Expression in the Cactus Opuntia ficus-indica1[C][W

    Science.gov (United States)

    Mallona, Izaskun; Egea-Cortines, Marcos; Weiss, Julia

    2011-01-01

    The cactus Opuntia ficus-indica is a constitutive Crassulacean acid metabolism (CAM) species. Current knowledge of CAM metabolism suggests that the enzyme phosphoenolpyruvate carboxylase kinase (PPCK) is circadian regulated at the transcriptional level, whereas phosphoenolpyruvate carboxylase (PEPC), malate dehydrogenase (MDH), NADP-malic enzyme (NADP-ME), and pyruvate phosphate dikinase (PPDK) are posttranslationally controlled. As little transcriptomic data are available from obligate CAM plants, we created an expressed sequence tag database derived from different organs and developmental stages. Sequences were assembled, compared with sequences in the National Center for Biotechnology Information nonredundant database for identification of putative orthologs, and mapped using Kyoto Encyclopedia of Genes and Genomes Orthology and Gene Ontology. We identified genes involved in circadian regulation and CAM metabolism for transcriptomic analysis in plants grown in long days. We identified stable reference genes for quantitative polymerase chain reaction and found that OfiSAND, like its counterpart in Arabidopsis (Arabidopsis thaliana), and OfiTUB are generally appropriate standards for use in the quantification of gene expression in O. ficus-indica. Three kinds of expression profiles were found: transcripts of OfiPPCK oscillated with a 24-h periodicity; transcripts of the light-active OfiNADP-ME and OfiPPDK genes adapted to 12-h cycles, while transcript accumulation patterns of OfiPEPC and OfiMDH were arrhythmic. Expression of the circadian clock gene OfiTOC1, similar to Arabidopsis, oscillated with a 24-h periodicity, peaking at night. Expression of OfiCCA1 and OfiPRR9, unlike in Arabidopsis, adapted best to a 12-h rhythm, suggesting that circadian clock gene interactions differ from those of Arabidopsis. Our results indicate that the evolution of CAM metabolism could be the result of modified circadian regulation at both the transcriptional and posttranscriptional

  2. Conserved and divergent rhythms of crassulacean acid metabolism-related and core clock gene expression in the cactus Opuntia ficus-indica.

    Science.gov (United States)

    Mallona, Izaskun; Egea-Cortines, Marcos; Weiss, Julia

    2011-08-01

    The cactus Opuntia ficus-indica is a constitutive Crassulacean acid metabolism (CAM) species. Current knowledge of CAM metabolism suggests that the enzyme phosphoenolpyruvate carboxylase kinase (PPCK) is circadian regulated at the transcriptional level, whereas phosphoenolpyruvate carboxylase (PEPC), malate dehydrogenase (MDH), NADP-malic enzyme (NADP-ME), and pyruvate phosphate dikinase (PPDK) are posttranslationally controlled. As little transcriptomic data are available from obligate CAM plants, we created an expressed sequence tag database derived from different organs and developmental stages. Sequences were assembled, compared with sequences in the National Center for Biotechnology Information nonredundant database for identification of putative orthologs, and mapped using Kyoto Encyclopedia of Genes and Genomes Orthology and Gene Ontology. We identified genes involved in circadian regulation and CAM metabolism for transcriptomic analysis in plants grown in long days. We identified stable reference genes for quantitative polymerase chain reaction and found that OfiSAND, like its counterpart in Arabidopsis (Arabidopsis thaliana), and OfiTUB are generally appropriate standards for use in the quantification of gene expression in O. ficus-indica. Three kinds of expression profiles were found: transcripts of OfiPPCK oscillated with a 24-h periodicity; transcripts of the light-active OfiNADP-ME and OfiPPDK genes adapted to 12-h cycles, while transcript accumulation patterns of OfiPEPC and OfiMDH were arrhythmic. Expression of the circadian clock gene OfiTOC1, similar to Arabidopsis, oscillated with a 24-h periodicity, peaking at night. Expression of OfiCCA1 and OfiPRR9, unlike in Arabidopsis, adapted best to a 12-h rhythm, suggesting that circadian clock gene interactions differ from those of Arabidopsis. Our results indicate that the evolution of CAM metabolism could be the result of modified circadian regulation at both the transcriptional and posttranscriptional

  3. Treatment of Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... amino acid metabolism disorders Treatment of amino acid metabolism disorders E-mail to a friend Please fill ... It's been added to your dashboard . Amino acid metabolism disorders are rare health conditions that affect a ...

  4. Efficient production of L-Lactic acid by metabolically engineered Saccharomyces cerevisiae with a genome-integrated L-lactate dehydrogenase gene.

    Science.gov (United States)

    Ishida, Nobuhiro; Saitoh, Satoshi; Tokuhiro, Kenro; Nagamori, Eiji; Matsuyama, Takashi; Kitamoto, Katsuhiko; Takahashi, Haruo

    2005-04-01

    We developed a metabolically engineered yeast which produces lactic acid efficiently. In this recombinant strain, the coding region for pyruvate decarboxylase 1 (PDC1) on chromosome XII is substituted for that of the l-lactate dehydrogenase gene (LDH) through homologous recombination. The expression of mRNA for the genome-integrated LDH is regulated under the control of the native PDC1 promoter, while PDC1 is completely disrupted. Using this method, we constructed a diploid yeast transformant, with each haploid genome having a single insertion of bovine LDH. Yeast cells expressing LDH were observed to convert glucose to both lactate (55.6 g/liter) and ethanol (16.9 g/liter), with up to 62.2% of the glucose being transformed into lactic acid under neutralizing conditions. This transgenic strain, which expresses bovine LDH under the control of the PDC1 promoter, also showed high lactic acid production (50.2 g/liter) under nonneutralizing conditions. The differences in lactic acid production were compared among four different recombinants expressing a heterologous LDH gene (i.e., either the bovine LDH gene or the Bifidobacterium longum LDH gene): two transgenic strains with 2microm plasmid-based vectors and two genome-integrated strains.

  5. Nutrigenomic studies on hilsa to evaluate flesh quality attributes and genes associated with fatty acid metabolism from the rivers Hooghly and Padma.

    Science.gov (United States)

    Ganguly, Satabdi; Mahanty, Arabinda; Mitra, Tandrima; Mohanty, Sasmita; Das, Basanta Kumar; Mohanty, Bimal Prasanna

    2018-01-01

    The Indian shad hilsa (Tenualosa ilisha), a commercially important food fish rich in oils, enjoys high consumer preference in the South Asian countries owing to its unique flavour and culinary properties. The present study was undertaken with the primary objective of determining the flesh quality attributes of hilsa in terms of nutritive value (gross chemical composition, amino acid, fatty acid and mineral composition), pH, water holding capacity (WHC) and expression of genes associated with fatty acid metabolism and flesh quality. Additionally, comparative studies on the flesh quality attributes in hilsa from two distributaries of river Ganga i.e. Hooghly and Padma were also carried out. A high WHC (>80%) suggested juicy and tender nature of hilsa meat. The protein content was 18-21% in hilsa from both the rivers and essential amino acid lysine, valine and functional amino acids leucine and arginine were significantly higher in Hooghly hilsa (Pattributes of hilsa has enriched the knowledgebase. Further, from comparative nutrient analysis on hilsa from river Hooghly and Padma, it was observed that Hooghly hilsa is superior in terms of oil content, ω-3 PUFAs EPA and DHA and essential amino acids; however, the expression profile of genes associated with flesh quality were found to be similar. Thus, within the scope of the present study, Hooghly hilsa (medium size category, 500-700g size) was found to be nutritionally superior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level.

    Science.gov (United States)

    Duan, Xiangke; Li, Yunsong; Du, Qinglin; Huang, Qinqin; Guo, Siyao; Xu, Mengmeng; Lin, Yanping; Liu, Zhidong; Xie, Jianping

    2016-01-25

    Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation, and possibly through altering the intracellular amino acid metabolism balance.

  7. The drought-tolerant Solanum pennellii regulates leaf water loss and induces genes involved in amino acid and ethylene/jasmonate metabolism under dehydration.

    Science.gov (United States)

    Egea, Isabel; Albaladejo, Irene; Meco, Victoriano; Morales, Belén; Sevilla, Angel; Bolarin, Maria C; Flores, Francisco B

    2018-02-12

    Breeding for drought-tolerant crops is a pressing issue due to the increasing frequency and duration of droughts caused by climate change. Although important sources of variation for drought tolerance exist in wild relatives, the mechanisms and the key genes controlling tolerance in tomato are little known. The aim of this study is to determine the drought response of the tomato wild relative Solanum pennellii (Sp) compared with the cultivated tomato Solanum lycopersicum (Sl). The paper investigates the physiological and molecular responses in leaves of Sp and Sl plants without stress and moderate drought stress. Significant physiological differences between species were found, with Sp leaves showing greater ability to avoid water loss and oxidative damage. Leaf transcriptomic analysis carried out when leaves did not as yet show visual dehydration symptoms revealed important constitutive expression differences between Sp and Sl species. Genes linked to different physiological and metabolic processes were induced by drought in Sp, especially those involved in N assimilation, GOGAT/GS cycle and GABA-shunt. Up-regulation in Sp of genes linked to JA/ET biosynthesis and signaling pathways was also observed. In sum, genes involved in the amino acid metabolism together with genes linked to ET/JA seem to be key actors in the drought tolerance of the wild tomato species.

  8. NanR, a Transcriptional Regulator That Binds to the Promoters of Genes Involved in Sialic Acid Metabolism in the Anaerobic Pathogen Clostridium perfringens.

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    Blair Therit

    Full Text Available Among many other virulence factors, Clostridium perfringens produces three sialidases NanH, NanI and NanJ. NanH lacks a secretion signal peptide and is predicted to be an intracellular enzyme, while NanI and NanJ are secreted. Previously, we had identified part of an operon encoding NanE (epimerase and NanA (sialic acid lyase enzymes. Further analysis of the entire operon suggests that it encodes a complete pathway for the transport and metabolism of sialic acid along with a putative transcriptional regulator, NanR. The addition of 30 mM N-acetyl neuraminic acid (Neu5Ac to a semi-defined medium significantly enhanced the growth yield of strain 13, suggesting that Neu5Ac can be used as a nutrient. C. perfringens strain 13 lacks a nanH gene, but has NanI- and NanJ-encoding genes. Analysis of nanI, nanJ, and nanInanJ mutants constructed by homologous recombination revealed that the expression of the major sialidase, NanI, was induced by the addition of Neu5Ac to the medium, and that in separate experiments, the same was true of a nanI-gusA transcriptional fusion. For the nanI and nanJ genes, primer extension identified three and two putative transcription start sites, respectively. Gel mobility shift assays using purified NanR and DNA from the promoter regions of the nanI and nanE genes showed high affinity, specific binding by NanR. We propose that NanR is a global regulator of sialic acid-associated genes and that it responds, in a positive feedback loop, to the concentration of sialic acid in the cell.

  9. NanR, a Transcriptional Regulator That Binds to the Promoters of Genes Involved in Sialic Acid Metabolism in the Anaerobic Pathogen Clostridium perfringens.

    Science.gov (United States)

    Therit, Blair; Cheung, Jackie K; Rood, Julian I; Melville, Stephen B

    2015-01-01

    Among many other virulence factors, Clostridium perfringens produces three sialidases NanH, NanI and NanJ. NanH lacks a secretion signal peptide and is predicted to be an intracellular enzyme, while NanI and NanJ are secreted. Previously, we had identified part of an operon encoding NanE (epimerase) and NanA (sialic acid lyase) enzymes. Further analysis of the entire operon suggests that it encodes a complete pathway for the transport and metabolism of sialic acid along with a putative transcriptional regulator, NanR. The addition of 30 mM N-acetyl neuraminic acid (Neu5Ac) to a semi-defined medium significantly enhanced the growth yield of strain 13, suggesting that Neu5Ac can be used as a nutrient. C. perfringens strain 13 lacks a nanH gene, but has NanI- and NanJ-encoding genes. Analysis of nanI, nanJ, and nanInanJ mutants constructed by homologous recombination revealed that the expression of the major sialidase, NanI, was induced by the addition of Neu5Ac to the medium, and that in separate experiments, the same was true of a nanI-gusA transcriptional fusion. For the nanI and nanJ genes, primer extension identified three and two putative transcription start sites, respectively. Gel mobility shift assays using purified NanR and DNA from the promoter regions of the nanI and nanE genes showed high affinity, specific binding by NanR. We propose that NanR is a global regulator of sialic acid-associated genes and that it responds, in a positive feedback loop, to the concentration of sialic acid in the cell.

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

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    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.

  11. Hepatic Metabolic, Inflammatory, and Stress-Related Gene Expression in Growing Mice Consuming a Low Dose of Trans-10, cis-12-Conjugated Linoleic Acid

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    Jing Li

    2012-01-01

    Full Text Available Dietary trans-10, cis-12-conjugated linoleic acid (trans-10, cis-12-CLA fed to obese and nonobese rodents reduces body fat but leads to greater liver mass due to steatosis. The molecular mechanisms accompanying such responses remain largely unknown. Our study investigated the effects of chronic low trans-10, cis-12-CLA supplementation on hepatic expression of 39 genes related to metabolism, inflammation, and stress in growing mice. Feeding a diet supplemented with 0.3% trans-10, cis-12-CLA (wt/wt basis for 6 weeks increased liver mass and concentration of long-chain fatty acids (LCFAs in liver, while adipose tissue mass decreased markedly. These changes were accompanied by greater expression of genes involved in LCFA uptake (Cd36, lipogenesis, and triacylglycerol synthesis (Acaca, Gpam, Scd, Pck1, Plin2. Expression of these genes was in line with upregulation of the lipogenic transcription factor Srebf1. Unlike previous studies where higher >0.50% of the diet doses of trans-10, cis-12-CLA were fed, we found greater expression of genes associated with VLDL assembly/secretion (Mttp, Cideb, ketogenesis (Hmgcs2, Bdh1, and LCFA oxidation (Acox1, Pdk4 in response to trans-10, cis-12-CLA. Dietary CLA, however, did not affect inflammation- and stress-related genes. Results suggested that a chronic low dose of dietary CLA increases liver mass and lipid accumulation due to activation of lipogenesis and insufficient induction of LCFA oxidation and VLDL assembly/secretion.

  12. Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer

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    Ramenghi Ugo

    2009-09-01

    Full Text Available Abstract Background Diamond-Blackfan anaemia (DBA is a rare inherited red cell hypoplasia characterised by a defect in the maturation of erythroid progenitors and in some cases associated with malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP genes, i.e RPS19, RPS24, RPS17, RPL5, RPL11, RPL35A. Studies in haematopoietic progenitors from patients show that haplo-insufficiency of an RP impairs rRNA processing and ribosome biogenesis. DBA lymphocytes show reduced protein synthesis and fibroblasts display abnormal rRNA processing and impaired proliferation. Results To evaluate the involvement of non-haematopoietic tissues in DBA, we have analysed global gene expression in fibroblasts from DBA patients compared to healthy controls. Microarray expression profiling using Affymetrix GeneChip Human Genome U133A 2.0 Arrays revealed that 421 genes are differentially expressed in DBA patient fibroblasts. These genes include a large cluster of ribosomal proteins and factors involved in protein synthesis and amino acid metabolism, as well as genes associated to cell death, cancer and tissue development. Conclusion This analysis reports for the first time an abnormal gene expression profile in a non-haematopoietic cell type in DBA. These data support the hypothesis that DBA may be due to a defect in general or specific protein synthesis.

  13. Regulation of metabolic flux in Lactobacillus casei for lactic acid production by overexpressed ldhL gene with two-stage oxygen supply strategy.

    Science.gov (United States)

    Ge, Xiang-Yang; Xu, Yan; Chen, Xiang; Zhang, Long-Yun

    2015-01-01

    This study describes a novel strategy to regulate the metabolic flux for lactic acid production in Lactobacillus casei. The ldhL gene encoding L-lactate dehydrogenase (L-LDH) was overexpressed in L. casei, and a two-stage oxygen supply strategy (TOS) that maintained a medium oxygen supply level during the early fermentation phase, and a low oxygen supply level in the later phase was carried out. As a consequence, a maximum L-LDH activity of 95.6 U/ml was obtained in the recombinant strain, which was over 4-fold higher than that of the initial strain. Under the TOS for L. casei (pMG-ldhL), the maximum lactic acid concentration of 159.6 g/l was obtained in 36 h, corresponding to a 62.8% increase. The results presented here provide a novel way to regulate the metabolic flux of L. casei for lactic acid production in different fermentation stages, which is available to enhance organic acid production in other strains.

  14. Tang-Nai-Kang alleviates pre-diabetes and metabolic disorders and induces a gene expression switch toward fatty acid oxidation in SHR.Cg-Leprcp/NDmcr rats.

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    Linyi Li

    Full Text Available Increased energy intake and reduced physical activity can lead to obesity, diabetes and metabolic syndrome. Transcriptional modulation of metabolic networks has become a focus of current drug discovery research into the prevention and treatment of metabolic disorders associated with energy surplus and obesity. Tang-Nai-Kang (TNK, a mixture of five herbal plant extracts, has been shown to improve abnormal glucose metabolism in patients with pre-diabetes. Here, we report the metabolic phenotype of SHR.Cg-Leprcp/NDmcr (SHR/cp rats treated with TNK. Pre-diabetic SHR/cp rats were randomly divided into control, TNK low-dose (1.67 g/kg and TNK high-dose (3.24 g/kg groups. After high-dose treatment for 2 weeks, the serum triglycerides and free fatty acids in SHR/cp rats were markedly reduced compared to controls. After 3 weeks of administration, the high dose of TNK significantly reduced the body weight and fat mass of SHR/cp rats without affecting food consumption. Serum fasting glucose and insulin levels in the TNK-treated groups decreased after 6 weeks of treatment. Furthermore, TNK-treated rats exhibited obvious improvements in glucose intolerance and insulin resistance. The improved glucose metabolism may be caused by the substantial reduction in serum lipids and body weight observed in SHR/cp rats starting at 3 weeks of TNK treatment. The mRNA expression of NAD+-dependent deacetylase sirtuin 1 (SIRT1 and genes related to fatty acid oxidation was markedly up-regulated in the muscle, liver and adipose tissue after TNK treatment. Furthermore, TNK promoted the deacetylation of two well-established SIRT1 targets, PPARγ coactivator 1α (PGC1α and forkhead transcription factor 1 (FOXO1, and induced the phosphorylation of AMP-activated protein kinase (AMPK and acetyl-CoA carboxylase (ACC in different tissues. These observations suggested that TNK may be an alternative treatment for pre-diabetes and metabolic syndrome by inducing a gene expression switch

  15. Serum uric acid levels and metabolic syndrome.

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    Ciarla, Sara; Struglia, Manuela; Giorgini, Paolo; Striuli, Rinaldo; Necozione, Stefano; Properzi, Giuliana; Ferri, Claudio

    2014-07-01

    To investigate the relationship among serum uric acid levels and metabolic syndrome. Anthropometric parameters, serum uric acid and metabolic parameters were evaluated in 139 subjects. Serum uric acid levels were significantly higher in subjects with than without metabolic syndrome (p metabolic syndrome components (p for trend uric acid significantly correlated with various anthropometric and serum metabolic parameters. Serum uric acid levels were higher in individuals with rather than without metabolic syndrome and raised gradually as the number of metabolic syndrome components increased. The relationship between serum uric acid levels and various metabolic parameters suggests that uric acid might be considered as a component of metabolic syndrome. Hyperuricemia is a common finding in patients with the metabolic syndrome. Recent studies indicated that hyperuricemia may be also a predictor of metabolic syndrome development.

  16. Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis.

    Science.gov (United States)

    Fang, Jing Yuan; Xiao, Shu Dong

    2003-01-01

    DNA methylation is the main epigenetic modification after replication in humans. DNA (cytosine-5)-methyltransferase (DNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to C5 of cytosine within CpG dinucleotide sequences in the genomic DNA of higher eukaryotes. There is considerable evidence that aberrant DNA methylation plays an integral role in carcinogenesis. Folic acid or folate is crucial for normal DNA synthesis and can regulate DNA methylation, and through this, it affects cellular SAM levels. Folate deficiency results in DNA hypomethylation. Epidemiological studies have indicated that folic acid protects against gastrointestinal (GI) cancers. Methylene-tetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are the enzymes involved in folate metabolism and are thought to influence DNA methylation. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Two common MTHFR polymorphisms, 677CT (or 677TT) and A1298C, and an MS polymorphism, A-->G at 2756, have been identified. Most studies support an inverse association between folate status and the rate of colorectal adenomas and carcinomas. During human GI carcinogenesis, MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level, as well as aberrant methylation.

  17. Expression profiles of genes and enzymes related to ascorbic acid metabolism in fruits of Ziziphus jujuba Mill. ´Jinsixiaozao´

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    Yingying CHEN,Zhihui ZHAO,Jin ZHAO,Mengjun LIU

    2016-06-01

    Full Text Available The fruit of Chinese jujube (Ziziphus jujuba possesses extremely high concentrations of ascorbic acid (AsA. The accumulation of AsA, the expression patterns of the nine genes related to AsA metabolism as well as the activities of five enzymes involved in AsA synthesis, oxidation and recycling were investigated during fruit development in Z. jujuba Mill. 'Jinsixiaozao'. The results showed that the high level of AsA accumulation in jujube fruit is due to a contribution from both AsA biosynthesis and AsA recycling. It is suggested that L-galactono-1,4-lactone dehydrogenase, ascorbate peroxidase and monodehydro-ascorbate reductase are the crucial genes/enzymes of jujube AsA synthesis, oxidization and recycling, respectively. These results provide useful new insights into the regulatory mechanisms of AsA accumulation in Chinese jujube.

  18. Mining the bitter melon (momordica charantia l. seed transcriptome by 454 analysis of non-normalized and normalized cDNA populations for conjugated fatty acid metabolism-related genes

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    Shipp Matthew J

    2010-11-01

    Full Text Available Abstract Background Seeds of Momordica charantia (bitter melon produce high levels of eleostearic acid, an unusual conjugated fatty acid with industrial value. Deep sequencing of non-normalized and normalized cDNAs from developing bitter melon seeds was conducted to uncover key genes required for biotechnological transfer of conjugated fatty acid production to existing oilseed crops. It is expected that these studies will also provide basic information regarding the metabolism of other high-value novel fatty acids. Results Deep sequencing using 454 technology with non-normalized and normalized cDNA libraries prepared from bitter melon seeds at 18 DAP resulted in the identification of transcripts for the vast majority of known genes involved in fatty acid and triacylglycerol biosynthesis. The non-normalized library provided a transcriptome profile of the early stage in seed development that highlighted the abundance of transcripts for genes encoding seed storage proteins as well as for a number of genes for lipid metabolism-associated polypeptides, including Δ12 oleic acid desaturases and fatty acid conjugases, class 3 lipases, acyl-carrier protein, and acyl-CoA binding protein. Normalization of cDNA by use of a duplex-specific nuclease method not only increased the overall discovery of genes from developing bitter melon seeds, but also resulted in the identification of 345 contigs with homology to 189 known lipid genes in Arabidopsis. These included candidate genes for eleostearic acid metabolism such as diacylglycerol acyltransferase 1 and 2, and a phospholipid:diacylglycerol acyltransferase 1-related enzyme. Transcripts were also identified for a novel FAD2 gene encoding a functional Δ12 oleic acid desaturase with potential implications for eleostearic acid biosynthesis. Conclusions 454 deep sequencing, particularly with normalized cDNA populations, was an effective method for mining of genes associated with eleostearic acid metabolism in

  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.

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    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 IMF content in BF muscle and significantly improve the fatty acid composition in different skeletal muscles accompanied by changes in the expression of genes involved in lipid metabolism, compared with those in the pigs that received adequate dietary protein (20 %), which might result in improved eating quality and nutritional value of the meat.

  20. CACODYLIC ACID (DMAV): METABOLISM AND ...

    Science.gov (United States)

    The cacodylic acid (DMAV) issue paper discusses the metabolism and pharmacokinetics of the various arsenical chemicals; evaluates the appropriate dataset to quantify the potential cancer risk to the organic arsenical herbicides; provides an evaluation of the mode of carcinogenic action (MOA) for DMAV including a consideration of the key events for bladder tumor formation in rats, other potential modes of action; and also considers the human relevance of the proposed animal MOA. As part of tolerance reassessment under the Food Quality Protection Act for the August 3, 2006 deadline, the hazard of cacodylic acid is being reassessed.

  1. Differences in Arachidonic Acid Levels and Fatty Acid Desaturase (FADS) Gene Variants in African Americans and European Americans with Diabetes/Metabolic Syndrome

    Science.gov (United States)

    Sergeant, Susan; Hugenschmidt, Christina E.; Rudock, Megan E.; Ziegler, Julie T.; Ivester, Priscilla; Ainsworth, Hannah C.; Vaidya, Dhananjay; Case, L. Douglas; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.; Mathias, Rasika A.; Chilton, Floyd H.

    2012-01-01

    Over the past 50 years, increases in dietary n-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, have been hypothesized to cause or exacerbate chronic inflammatory diseases. This study examines an individual’s innate capacity to synthesize n-6-long chain PUFAs (LC-PUFAs), with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes/metabolic syndrome. Compared to European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7.9±2.1; AfAm 9.8±1.9 % of total fatty acids, mean ± sd; pFADS1 activity (EAm 5.4±2.2, AfAm 6.9±2.2; p=1.44×10−5). Seven single nucleotide polymorphisms (SNP) mapping to the FADS locus revealed strong association with AA, eicosapentaenoic acid (EPA) and dihomogamma-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT: 6.3±1.0; GG: 8.5±2.1; p=3.0×10−5) and AA/DGLA ratios (TT: 3.4±0.8; GG: 6.5±2.3; p=2.2×10−7) but higher DGLA levels (TT: 1.9±0.4; GG: 1.4±0.4; p=3.3×10−7) compared to those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0.81) compared to EAm (0.46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are likely important differences in the capacity of different populations to synthesize LC-PUFAs. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent. PMID:21733300

  2. Metabolic engineering of Rhizopus oryzae: Effects of overexpressing pyc and pepc genes on fumaric acid biosynthesis from glucose

    Science.gov (United States)

    Fumaric acid, a dicarboxylic acid used as a food acidulant and in manufacturing synthetic resins, can be produced from glucose in fermentation by Rhizopus oryzae. However, the fumaric acid yield is limited by the co-production of ethanol and other byproducts. To increase fumaric acid production, ove...

  3. Gene expression and metabolite profiling of developing highbush blueberry fruit indicates transcriptional regulation of flavonoid metabolism and activation of abscisic acid metabolism.

    Science.gov (United States)

    Zifkin, Michael; Jin, Alena; Ozga, Jocelyn A; Zaharia, L Irina; Schernthaner, Johann P; Gesell, Andreas; Abrams, Suzanne R; Kennedy, James A; Constabel, C Peter

    2012-01-01

    Highbush blueberry (Vaccinium corymbosum) fruits contain substantial quantities of flavonoids, which are implicated in a wide range of health benefits. Although the flavonoid constituents of ripe blueberries are known, the molecular genetics underlying their biosynthesis, localization, and changes that occur during development have not been investigated. Two expressed sequence tag libraries from ripening blueberry fruit were constructed as a resource for gene identification and quantitative real-time reverse transcription-polymerase chain reaction primer design. Gene expression profiling by quantitative real-time reverse transcription-polymerase chain reaction showed that flavonoid biosynthetic transcript abundance followed a tightly regulated biphasic pattern, and transcript profiles were consistent with the abundance of the three major classes of flavonoids. Proanthocyanidins (PAs) and corresponding biosynthetic transcripts encoding anthocyanidin reductase and leucoanthocyanidin reductase were most concentrated in young fruit and localized predominantly to the inner fruit tissue containing the seeds and placentae. Mean PA polymer length was seven to 8.5 subunits, linked predominantly via B-type linkages, and was relatively constant throughout development. Flavonol accumulation and localization patterns were similar to those of the PAs, and the B-ring hydroxylation pattern of both was correlated with flavonoid-3'-hydroxylase transcript abundance. By contrast, anthocyanins accumulated late in maturation, which coincided with a peak in flavonoid-3-O-glycosyltransferase and flavonoid-3'5'-hydroxylase transcripts. Transcripts of VcMYBPA1, which likely encodes an R2R3-MYB transcriptional regulator of PA synthesis, were prominent in both phases of development. Furthermore, the initiation of ripening was accompanied by a substantial rise in abscisic acid, a growth regulator that may be an important component of the ripening process and contribute to the regulation of

  4. Gene Expression and Metabolite Profiling of Developing Highbush Blueberry Fruit Indicates Transcriptional Regulation of Flavonoid Metabolism and Activation of Abscisic Acid Metabolism1[W][OA

    Science.gov (United States)

    Zifkin, Michael; Jin, Alena; Ozga, Jocelyn A.; Zaharia, L. Irina; Schernthaner, Johann P.; Gesell, Andreas; Abrams, Suzanne R.; Kennedy, James A.; Constabel, C. Peter

    2012-01-01

    Highbush blueberry (Vaccinium corymbosum) fruits contain substantial quantities of flavonoids, which are implicated in a wide range of health benefits. Although the flavonoid constituents of ripe blueberries are known, the molecular genetics underlying their biosynthesis, localization, and changes that occur during development have not been investigated. Two expressed sequence tag libraries from ripening blueberry fruit were constructed as a resource for gene identification and quantitative real-time reverse transcription-polymerase chain reaction primer design. Gene expression profiling by quantitative real-time reverse transcription-polymerase chain reaction showed that flavonoid biosynthetic transcript abundance followed a tightly regulated biphasic pattern, and transcript profiles were consistent with the abundance of the three major classes of flavonoids. Proanthocyanidins (PAs) and corresponding biosynthetic transcripts encoding anthocyanidin reductase and leucoanthocyanidin reductase were most concentrated in young fruit and localized predominantly to the inner fruit tissue containing the seeds and placentae. Mean PA polymer length was seven to 8.5 subunits, linked predominantly via B-type linkages, and was relatively constant throughout development. Flavonol accumulation and localization patterns were similar to those of the PAs, and the B-ring hydroxylation pattern of both was correlated with flavonoid-3′-hydroxylase transcript abundance. By contrast, anthocyanins accumulated late in maturation, which coincided with a peak in flavonoid-3-O-glycosyltransferase and flavonoid-3′5′-hydroxylase transcripts. Transcripts of VcMYBPA1, which likely encodes an R2R3-MYB transcriptional regulator of PA synthesis, were prominent in both phases of development. Furthermore, the initiation of ripening was accompanied by a substantial rise in abscisic acid, a growth regulator that may be an important component of the ripening process and contribute to the regulation

  5. Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

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    Teresa Auguet

    2014-12-01

    Full Text Available Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD. We aimed to evaluate gene expression of different fatty acid (FA metabolism-related genes in morbidly obese (MO women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS, FA uptake and transport (PPARγ, CD36, FABP4, FA oxidation (PPARα, and inflammation (IL6, TNFα, CRP, PPARδ were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13, simple steatosis (SS, n = 47 and non-alcoholic steatohepatitis (NASH, n = 67. Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively. Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively. Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.

  6. Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Auguet, Teresa; Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Porras, José Antonio; Aragonès, Gemma; Sabench, Fátima; Hernandez, Mercé; Aguilar, Carmen; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2014-01-01

    Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis. PMID:25474087

  7. Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome.

    Science.gov (United States)

    Sergeant, Susan; Hugenschmidt, Christina E; Rudock, Megan E; Ziegler, Julie T; Ivester, Priscilla; Ainsworth, Hannah C; Vaidya, Dhananjay; Case, L Douglas; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W; Mathias, Rasika A; Chilton, Floyd H

    2012-02-01

    Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid, have been hypothesised to cause or exacerbate chronic inflammatory diseases. The present study examines an individual's innate capacity to synthesise n-6 long-chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes or the metabolic syndrome. Compared with European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7·9 (sd 2·1), AfAm 9·8 (sd 1·9) % of total fatty acids; P FADS1 activity (EAm 5·4 (sd 2·2), AfAm 6·9 (sd 2·2); P = 1·44 × 10⁻⁵). In all, seven SNP mapping to the FADS locus revealed strong association with AA, EPA and dihomo-γ-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT 6·3 (sd 1·0); GG 8·5 (sd 2·1); P = 3·0 × 10⁻⁵) and AA:DGLA ratios (TT 3·4 (sd 0·8), GG 6·5 (sd 2·3); P = 2·2 × 10⁻⁷) but higher DGLA levels (TT 1·9 (sd 0·4), GG 1·4 (sd 0·4); P = 3·3 × 10⁻⁷) compared with those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0·81) compared with EAm (0·46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are probably important differences in the capacity of different populations to synthesise LC-PUFA. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent.

  8. Digital Cushion Fatty Acid Composition and Lipid Metabolism Gene Network Expression in Holstein Dairy Cows Fed a High-Energy Diet.

    Directory of Open Access Journals (Sweden)

    Zeeshan Muhammad Iqbal

    Full Text Available The hoof digital cushion is a complex structure composed of adipose tissue beneath the distal phalanx, i.e. axial, middle and abaxial fat pad. The major role of these fat depots is dampening compression of the corium underneath the cushion. The study aimed to determine expression of target genes and fatty acid profiles in the hoof of non-pregnant dry Holstein cows fed low (CON or high-energy (OVE diets. The middle fat pad of the hoof digital cushion was collected soon after slaughter. Despite the lack of effect on expression of the transcription regulators SREBF1 and PPARG, the expression of the lipogenic enzymes ACACA, FASN, SCD, and DGAT2 was upregulated with OVE. Along with the upregulation of G6PD and IDH1, important for NADPH synthesis during lipogenesis, and the basal glucose transporter SLC2A1, these data indicated a pro-lipogenic response in the digital cushion with OVE. The expression of the lipid droplet-associated protein PLIN2 was upregulated while expression of lipolytic enzymes (ATGL, ABDH5, and LIPE only tended to be upregulated with OVE. Therefore, OVE induced lipogenesis, lipid droplet formation, and lipolysis, albeit to different extents. Although concentration of monounsaturated fatty acids (MUFA did not differ, among the polyunsaturated fatty acids (PUFA, the concentration of 20:5n3 was lower with OVE. Among the saturated fatty acids, 20:0 concentration was greater with OVE. Although data indicated that the hoof digital cushion metabolic transcriptome is responsive to higher-energy diets, this did not translate into marked differences in the fatty acid composition. The decrease in concentration of PUFA, which could contribute to synthesis of inflammatory molecules, in OVE-fed cows indicated that feeding higher-energy diets might be detrimental for the mediation of inflammation in digital cushion. This effect could be further exacerbated by physiologic and endocrine changes during the peripartal period that favor inflammation.

  9. Amino acids: metabolism, functions, and nutrition.

    Science.gov (United States)

    Wu, Guoyao

    2009-05-01

    Recent years have witnessed the discovery that amino acids (AA) are not only cell signaling molecules but are also regulators of gene expression and the protein phosphorylation cascade. Additionally, AA are key precursors for syntheses of hormones and low-molecular weight nitrogenous substances with each having enormous biological importance. Physiological concentrations of AA and their metabolites (e.g., nitric oxide, polyamines, glutathione, taurine, thyroid hormones, and serotonin) are required for the functions. However, elevated levels of AA and their products (e.g., ammonia, homocysteine, and asymmetric dimethylarginine) are pathogenic factors for neurological disorders, oxidative stress, and cardiovascular disease. Thus, an optimal balance among AA in the diet and circulation is crucial for whole body homeostasis. There is growing recognition that besides their role as building blocks of proteins and polypeptides, some AA regulate key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. They are called functional AA, which include arginine, cysteine, glutamine, leucine, proline, and tryptophan. Dietary supplementation with one or a mixture of these AA may be beneficial for (1) ameliorating health problems at various stages of the life cycle (e.g., fetal growth restriction, neonatal morbidity and mortality, weaning-associated intestinal dysfunction and wasting syndrome, obesity, diabetes, cardiovascular disease, the metabolic syndrome, and infertility); (2) optimizing efficiency of metabolic transformations to enhance muscle growth, milk production, egg and meat quality and athletic performance, while preventing excess fat deposition and reducing adiposity. Thus, AA have important functions in both nutrition and health.

  10. 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

  11. Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA and risk for Crohn's disease in children & young adults.

    Directory of Open Access Journals (Sweden)

    Irina Costea

    2010-12-01

    Full Text Available Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA in Crohn's disease (CD is unclear, although the key metabolite leucotriene B4 (LTB(4 is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD.A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children ≤20 yrs diagnosed with CD and controls were recruited. 19 single nucleotide polymorphisms (SNPs across the ALOX5 (4 CYP4F3 (5 and CYP4F2 (10 genes, were genotyped. Associations between SNPs/haplotypes and CD were examined. A total of 431 cases and 507 controls were studied. The mean (±SD age of the cases was 12.4 (±3.3 years. Most cases were male (56.4%, had ileo-colonic disease (L3±L4, 52.7% and inflammatory behavior (B1±p, 87% at diagnosis. One genotyped CYP4F3 SNP (rs2683037 not in Hardy-Weinberg Equilibrium was excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident. However haplotype analysis revealed associations with a two-marker haplotype (TG (rs3794987 & rs1290617 (p = 0.02; permuted p = 0.08. CYP4F2 SNPs, rs3093158 (OR (recessive = 0.56, 95% CI = 0.35-0.89; p = 0.01, rs2074902 (OR (trend = 1.26, 95% CI = 1.00-1.60; p = 0.05, and rs2108622 (OR (recessive = 1.6, 95% CI = 1.00-2.57; p = 0.05 were significantly associated whereas rs1272 (OR (recessive = 0.58, 95% CI = 0.30-1.13; p = 0.10 showed suggestions for associations with CD. A haplotype comprising these 4 SNPs was significantly associated (p = 0.007, permuted p = 0.02 with CD. Associations with SNP rs3780901 in the ALOX5 gene were borderline non-significant (OR (dominant = 1.29, 95% CI = 0.99-1.67; p = 0.056. A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036 was associated with CD, but did not withstand corrections for multiple comparisons (permuted p = 0

  12. Articulation of three core metabolic processes in Arabidopsis: Fatty acid biosynthesis, leucine catabolism and starch metabolism

    Directory of Open Access Journals (Sweden)

    Nikolau Basil J

    2008-07-01

    Full Text Available Abstract Background Elucidating metabolic network structures and functions in multicellular organisms is an emerging goal of functional genomics. We describe the co-expression network of three core metabolic processes in the genetic model plant Arabidopsis thaliana: fatty acid biosynthesis, starch metabolism and amino acid (leucine catabolism. Results These co-expression networks form modules populated by genes coding for enzymes that represent the reactions generally considered to define each pathway. However, the modules also incorporate a wider set of genes that encode transporters, cofactor biosynthetic enzymes, precursor-producing enzymes, and regulatory molecules. We tested experimentally the hypothesis that one of the genes tightly co-expressed with starch metabolism module, a putative kinase AtPERK10, will have a role in this process. Indeed, knockout lines of AtPERK10 have an altered starch accumulation. In addition, the co-expression data define a novel hierarchical transcript-level structure associated with catabolism, in which genes performing smaller, more specific tasks appear to be recruited into higher-order modules with a broader catabolic function. Conclusion Each of these core metabolic pathways is structured as a module of co-expressed transcripts that co-accumulate over a wide range of environmental and genetic perturbations and developmental stages, and represent an expanded set of macromolecules associated with the common task of supporting the functionality of each metabolic pathway. As experimentally demonstrated, co-expression analysis can provide a rich approach towards understanding gene function.

  13. The diagnosis of inherited metabolic diseases by microarray gene expression profiling

    OpenAIRE

    Arenas Hernandez, Monica; Schulz, Reiner; Chaplin, Tracy; Young, Bryan D; Perrett, David; Champion, Michael P; Taanman, Jan-Willem; Fensom, Anthony; Marinaki, Anthony M

    2010-01-01

    Abstract Background Inherited metabolic diseases (IMDs) comprise a diverse group of generally progressive genetic metabolic disorders of variable clinical presentations and severity. We have undertaken a study using microarray gene expression profiling of cultured fibroblasts to investigate 68 patients with a broad range of suspected metabolic disorders, including defects of lysosomal, mitochondrial, peroxisomal, fatty acid, carbohydrate, amino acid, molybdenum cofactor, and purine and pyrimi...

  14. Intestinal metabolism of fatty acids.

    Science.gov (United States)

    Enser, M

    1965-08-01

    1. The effect of concentration on the oxidation and incorporation into lipids of lauric acid and linoleic acid by rings of rat small intestine has been studied in vitro. 2. In the absence of glucose, the oxidation of lauric acid in the range 0.01-5.0mm showed a maximum at 0.1mm. In the presence of glucose the maximum was at 0.5mm. The oxidation of linoleic acid in the presence of glucose increased throughout the concentration range 0.01-5.0mm. 3. The incorporation of lauric acid into lipids was maximal at 0.5-0.6mm in the presence of glucose, but at 10mm in the absence of glucose. At 0.8mm-lauric acid, in the presence of glucose, over 75% of the incorporated lauric acid was in triglycerides, but at 10mm they only contained 30%. The incorporation of glucose carbon into glycerides paralleled the incorporation of lauric acid. 4. In the range 0.01-2.5mm-linoleic acid the quantity incorporated into lipids increased. In the range 0.01-0.4mm linoleic acid was incorporated predominantly into triglycerides, but between 0.4 and 1.0mm most was in diglycerides, and between 2.5 and 5.0mm most was in monoglycerides. 5. The relationship of fatty acid concentration to the mechanism of absorption is discussed, together with the correlation between the distribution of the absorbed fatty acids within the tissue lipids and the lipase activity of intestinal mucosa.

  15. MITOCHONDRIAL AND METABOLIC GENE EXPRESSION IN THE AGED RAT HEART

    Directory of Open Access Journals (Sweden)

    Gregory P Barton

    2016-08-01

    Full Text Available Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function and AMP-activated protein kinase (AMPK activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo, Old (33 mo, and old exercise trained (Old + EXE (34 mo FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05 expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α, peroxisome proliferator activated receptor alpha (PPARα, and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function are superfluous and decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity and mitochondrial function in the heart.

  16. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... 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...

  17. Nucleotide Metabolism and its Control in Lactic Acid Bacteria

    DEFF Research Database (Denmark)

    Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal

    2005-01-01

    Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...... the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria....

  18. Metabolism and Residues of 2,4-Dichlorophenoxyacetic Acid in DAS-40278-9 Maize (Zea mays) Transformed with Aryloxyalkanoate Dioxygenase-1 Gene.

    Science.gov (United States)

    Zhou, Xiao; Rotondaro, Sandra L; Ma, Mingming; Rosser, Steve W; Olberding, Ed L; Wendelburg, Brian M; Adelfinskaya, Yelena A; Balcer, Jesse L; Blewett, T Craig; Clements, Bruce

    2016-10-12

    DAS-40278-9 maize, which is developed by Dow AgroSciences, has been genetically modified to express the aryloxyalkanoate dioxygenase-1 (AAD-1) protein and is tolerant to phenoxy auxin herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D). To understand the metabolic route and residue distribution of 2,4-D in DAS-40278-9 maize, a metabolism study was conducted with 14C-radiolabeled 2,4-D applied at the maximum seasonal rate. Plants were grown in boxes outdoors. Forage and mature grain, cobs, and stover were collected for analysis. The metabolism study showed that 2,4-D was metabolized to 2,4-dichlorophenol (2,4-DCP), which was then rapidly conjugated with glucose. Field-scale residue studies with 2,4-D applied at the maximum seasonal rate were conducted at 25 sites in the U.S. and Canada to measure the residues of 2,4-D and free and conjugated 2,4-DCP in mature forage, grain, and stover. Residues of 2,4-D were not detectable in the majority of the grain samples and averaged <1.0 and <1.5 μg/g in forage and stover, respectively. Free plus conjugated 2,4-DCP was not observed in grain and averaged <1.0 μg/g in forage and stover.

  19. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

    DEFF Research Database (Denmark)

    Hernández-Alvarez, María Isabel; Díaz-Ramos, Angels; Berdasco, María

    2017-01-01

    The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused...... that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis...

  20. Metabolic enzymes in gene control

    NARCIS (Netherlands)

    E. Kozhevnikova (Elena)

    2012-01-01

    textabstractCellular compartments are believed to serve functional separation within the cell and allow it to perform multiple metabolic processes at the same time. Processes are divided between compartments with respect to the physiological requirements for a certain process. Thus, regulatory

  1. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel

    2016-01-01

    Full Text Available Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

  2. Research Progress of Amino Acid Metabolism PET Imaging in Tumor

    Directory of Open Access Journals (Sweden)

    NIE Da-hong

    2015-11-01

    Full Text Available Amino acid metabolism PET imaging plays a very important role in metabolism molecular imaging. Amino acid PET tracers include [1-11C]amino acid, labeling α-C amino acid, labeling side-chain amino acid, and N-substituted labeling amino acid. Uptake mechanism of these amino acids in tumor mainly involves in amino acid transport and amino acid metabolism PET imaging has an advantage of differential diagnosis of neuropsychiatric diseases, brain cancer, neuroendocrine tumor, and other tumors. The research progress of amino acid metabolism PET imaging in tumor were summarized.

  3. Metabolic engineering of chloroplasts for artemisinic acid ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 39; Issue 1. Metabolic engineering of chloroplasts for artemisinic acid biosynthesis and impact on plant growth ... International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India; School of Science Engineering and Technology, ...

  4. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  5. Dietary fatty acid metabolism in prediabetes.

    Science.gov (United States)

    Noll, Christophe; Carpentier, André C

    2017-02-01

    Experimental evidences are strong for a role of long-chain saturated fatty acids in the development of insulin resistance and type 2 diabetes. Ectopic accretion of triglycerides in lean organs is a characteristic of prediabetes and type 2 diabetes and has been linked to end-organ complications. The contribution of disordered dietary fatty acid (DFA) metabolism to lean organ overexposure and lipotoxicity is still unclear, however. DFA metabolism is very complex and very difficult to study in vivo in humans. We have recently developed a novel imaging method using PET with oral administration of 14-R,S-F-fluoro-6-thia-heptadecanoic acid (FTHA) to quantify organ-specific DFA partitioning. Our studies thus far confirmed impaired storage of DFA per volume of fat mass in abdominal adipose tissues of individuals with prediabetes. They also highlighted the increased channeling of DFA toward the heart, associated with subclinical reduction in cardiac systolic and diastolic function in individuals with prediabetes. In the present review, we summarize previous work on DFA metabolism in healthy and prediabetic states and discuss these in the light of our novel findings using PET imaging of DFA metabolism. We herein provide an integrated view of abnormal organ-specific DFA partitioning in prediabetes in humans.

  6. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism

    National Research Council Canada - National Science Library

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-01-01

    .... We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells...

  7. Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder

    Science.gov (United States)

    Moe, Orson W.

    2014-01-01

    Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. PMID:25045326

  8. Metabolic gene polymorphism frequencies in control populations.

    NARCIS (Netherlands)

    Garte, S.; Gaspari, L.; Alexandrie, A.K.; Ambrosone, C.; Autrup, H.; Autrup, J.L.; Baranova, H.; Bathum, L.; Benhamou, S.; Boffetta, P.; Bouchardy, C.; Breskvar, K.; Brockmoller, J.; Cascorbi, I.; Clapper, M.L.; Coutelle, C.; Daly, A.; Dell'Omo, M.; Dolzan, V.; Dresler, C.M.; Fryer, A.; Haugen, A.; Hein, D.W.; Hildesheim, A.; Hirvonen, A.; Hsieh, L.L.; Ingelman-Sundberg, M.; Kalina, I.; Kang, D.; Kihara, M.; Kiyohara, C.; Kremers, P.; Lazarus, P.; Marchand, L. le; Lechner, M.C.; Lieshout, E.M.M. van; London, S.; Manni, J.J.; Maugard, C.M.; Morita, S.; Nazar-Stewart, V.; Noda, K.; Oda, Y.; Parl, F.F.; Pastorelli, R.; Persson, I.; Peters, W.H.M.; Rannug, A.; Rebbeck, T.R.; Risch, A.; Roelandt, L.; Romkes, M.; Ryberg, D.; Salagovic, J.; Schoket, B.; Seidegard, J.; Shields, P.G.; Sim, E.; Sinnet, D.; Strange, R.C.; Stucker, I.; Sugimura, H.; To-Figueras, J.; Vineis, P.; Yu, M.C.; Taioli, E.

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1,

  9. Metabolic gene polymorphism frequencies in control populations

    DEFF Research Database (Denmark)

    Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT...

  10. Daily intake of conjugated linoleic acid-enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects.

    Science.gov (United States)

    Nazare, Julie-Anne; de la Perrière, Aude Brac; Bonnet, Fabrice; Desage, Michel; Peyrat, Jocelyne; Maitrepierre, Christine; Louche-Pelissier, Corinne; Bruzeau, Joëlle; Goudable, Joëlle; Lassel, Taous; Vidal, Hubert; Laville, Martine

    2007-02-01

    Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The present study was designed to determine whether 14-week CLA supplementation as triacylglycerols (3.76 g) with a 50 : 50 combination of the two main isomers (35 % cis-9, trans-11 and 35 % trans-10, cis-12) added to flavoured yoghurt-like products was able to alter body composition in healthy subjects and to alter the expression of several key adipose tissue genes (PPAR gamma, lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and uncoupling protein 2 (UCP-2)). Forty-four healthy subjects were randomly assigned to consume daily either a CLA-supplemented yoghurt-like product or a placebo yoghurt for 98 d. There were no significant effects of CLA supplementation on body weight, fat mass or free fat mass. Basal energy expenditure expressed as kg free fat mass increased significantly in the CLA group (123.3 (SEM 2.5) kJ/kg free fat mass per d on day 98 v. 118.7 (SEM 2.3) kJ/kg free fat mass per d on day 0, P = 0.03). PPAR gamma mRNA gene expression increased significantly with CLA supplementation (53 (SEM 20) %, P supplementation diet with a 50 : 50 mixture of the two CLA isomers cis-9, trans-11 and trans-10, cis-12 in a dairy product was unable to alter body composition, although a significant increase in the RMR has been induced. Moreover, changes in mRNA PPAR gamma and HSL in adipose tissue were recorded.

  11. Crassulacean acid metabolism in submerged aquatic plants

    Science.gov (United States)

    Keeley, Jon E.; Sybesme, C.

    1984-01-01

    CO2-fixation in the dark is known to occur in various organs of many plants. However, only in species possessing crassulacean acid metabolism (CAM) does dark CO2-fixation contribute substantially to the carbon economy of the plant. Until very recently CAM was known only from terrestrial species, largely drought adapted succulents. The discovery of CAM in the submerged aquatic fern ally Isoetes howellii (Isoetaceae)(Keeley 1981) adds a new dimension to our understanding of crassulacean acid metabolism. In this paper I will summarize 1) the evidence of CAM in Isoetes howellii, 2) the data on the distribution of CAM in aquatic species, and 3) the work to date on the functional significance of CAM in aquatic species.

  12. A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

    Science.gov (United States)

    Cuthbert, Candace E; Foster, Jerome E; Ramdath, D Dan

    2017-10-01

    A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (Pinsulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

  13. Metabolic acid-base disorders in the critical care unit.

    Science.gov (United States)

    de Morais, Helio Autran; Bach, Jonathan F; DiBartola, Stephen P

    2008-05-01

    The recognition and management of acid-base disorders is a commonplace activity in the critical care unit, and the role of weak and strong acids in the genesis of metabolic acid-base disorders is reviewed. The clinical approach to patients with metabolic alkalosis and metabolic acidosis is discussed in this article.

  14. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were...... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  15. Amino acid metabolic signaling influences Aedes aegypti midgut microbiome variability.

    Directory of Open Access Journals (Sweden)

    Sarah M Short

    2017-07-01

    Full Text Available The mosquito midgut microbiota has been shown to influence vector competence for multiple human pathogens. The microbiota is highly variable in the field, and the sources of this variability are not well understood, which limits our ability to understand or predict its effects on pathogen transmission. In this work, we report significant variation in female adult midgut bacterial load between strains of A. aegypti which vary in their susceptibility to dengue virus. Composition of the midgut microbiome was similar overall between the strains, with 81-92% of reads coming from the same five bacterial families, though we did detect differences in the presence of some bacterial families including Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on the two mosquito strains that showed the greatest difference in bacterial load, and found that they differ in transcript abundance of many genes implicated in amino acid metabolism, in particular the branched chain amino acid degradation pathway. We then silenced this pathway by targeting multiple genes using RNA interference, which resulted in strain-specific bacterial proliferation, thereby eliminating the difference in midgut bacterial load between the strains. This suggests that the branched chain amino acid (BCAA degradation pathway controls midgut bacterial load, though the mechanism underlying this remains unclear. Overall, our results indicate that amino acid metabolism can act to influence the midgut microbiota. Moreover, they suggest that genetic or physiological variation in BCAA degradation pathway activity may in part explain midgut microbiota variation in the field.

  16. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2012-01-01

    Full Text Available Obesity, diabetes, and metabolic syndromes are increasingly recognized as health concerns worldwide. Overnutrition and insulin resistance are the major causes of diabetic hyperglycemia and hyperlipidemia in humans. Studies in the past decade provide evidence that bile acids are not just biological detergents facilitating gut nutrient absorption, but also important metabolic regulators of glucose and lipid homeostasis. Pharmacological alteration of bile acid metabolism or bile acid signaling pathways such as using bile acid receptor agonists or bile acid binding resins may be a promising therapeutic strategy for the treatment of obesity and diabetes. On the other hand, bile acid signaling is complex, and the molecular mechanisms mediating the bile acid effects are still not completely understood. This paper will summarize recent advances in our understanding of bile acid signaling in regulation of glucose and lipid metabolism, and the potentials of developing novel therapeutic strategies that target bile acid metabolism for the treatment of metabolic disorders.

  17. Cloning of genes related to aliphatic glucosinolate metabolism and the mechanism of sulforaphane accumulation in broccoli sprouts under jasmonic acid treatment.

    Science.gov (United States)

    Guo, Liping; Yang, Runqiang; Gu, Zhenxin

    2016-10-01

    Cytochrome P450 79F1 (CYP79F1), cytochrome P450 83A1 (CYP83A1), UDP-glucosyltransferase 74B1 (UGT74B1), sulfotransferase 18 (ST5b) and flavin-containing monooxygenase GS-OX1 (FMOGS - OX1 ) are important enzymes in aliphatic glucosinolate biosynthesis. In this study, their full-length cDNA in broccoli was firstly cloned, then the mechanism of sulforaphane accumulation under jasmonic acid (JA) treatment was investigated. The full-length cDNA of CYP79F1, CYP83A1, UGT74B1, ST5b and FMOGS - OX1 comprised 1980, 1652, 1592, 1378 and 1623 bp respectively. The increase in aliphatic glucosinolate accumulation in broccoli sprouts treated with JA was associated with elevated expression of genes in the aliphatic glucosinolate biosynthetic pathway. Application of 100 µmol L(-1) JA increased myrosinase (MYR) activity but did not affect epithiospecifier protein (ESP) activity in broccoli sprouts, which was supported by the expression of MYR and ESP. Sulforaphane formation in 7-day-old sprouts treated with 100 µmol L(-1) JA was 3.36 and 1.30 times that in the control and 300 µmol L(-1) JA treatment respectively. JA enhanced the accumulation of aliphatic glucosinolates in broccoli sprouts via up-regulation of related gene expression. Broccoli sprouts treated with 100 µmol L(-1) JA showed higher sulforphane formation than those treated with 300 µmol L(-1) JA owing to the higher glucoraphanin content and myrosinase activity under 100 µmol L(-1) JA treatment. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. Identification of C4 photosynthesis metabolism and regulatory-associated genes in Eleocharis vivipara by SSH.

    Science.gov (United States)

    Chen, Taiyu; Ye, Rongjian; Fan, Xiaolei; Li, Xianghua; Lin, Yongjun

    2011-09-01

    This is the first effort to investigate the candidate genes involved in kranz developmental regulation and C(4) metabolic fluxes in Eleocharis vivipara, which is a leafless freshwater amphibious plant and possesses a distinct culms anatomy structure and photosynthetic pattern in contrasting environments. A terrestrial specific SSH library was constructed to investigate the genes involved in kranz anatomy developmental regulation and C(4) metabolic fluxes. A total of 73 ESTs and 56 unigenes in 384 clones were identified by array hybridization and sequencing. In total, 50 unigenes had homologous genes in the databases of rice and Arabidopsis. The real-time quantitative PCR results showed that most of the genes were accumulated in terrestrial culms and ABA-induced culms. The C(4) marker genes were stably accumulated during the culms development process in terrestrial culms. With respect to C(3) culms, C(4) photosynthesis metabolism consumed much more transporters and translocators related to ion metabolism, organic acids and carbohydrate metabolism, phosphate metabolism, amino acids metabolism, and lipids metabolism. Additionally, ten regulatory genes including five transcription factors, four receptor-like proteins, and one BURP protein were identified. These regulatory genes, which co-accumulated with the culms developmental stages, may play important roles in culms structure developmental regulation, bundle sheath chloroplast maturation, and environmental response. These results shed new light on the C(4) metabolic fluxes, environmental response, and anatomy structure developmental regulation in E. vivipara.

  19. Metabolic engineering of Mannheimia succiniciproducens for succinic acid production based on elementary mode analysis with clustering.

    Science.gov (United States)

    Kim, Won Jun; Ahn, Jung Ho; Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

    2017-02-01

    Mannheimia succiniciproducens, a capnophilic gram-negative rumen bacterium, has been employed for the efficient production of succinic acid. Although M. succiniciproducens metabolism was previously studied using a genome-scale metabolic model, more metabolic characteristics are to be understood. To this end, elementary mode analysis accompanied with clustering ('EMC' analysis) is used to gain further insights on metabolic characteristics of M. succiniciproducens allowing efficient succinic acid production. Elementary modes (EMs) generated from the central carbon metabolic network of M. succiniciproducens are clustered to systematically analyze succinic acid production routes. Based on the results of EMC analysis, zwf gene is identified as a novel overexpression target for the improved succinic acid production. This gene is overexpressed in a previously constructed succinic acid-overproducing M. succiniciproducens LPK7 strain. Heterologous NADPH-dependent mdh is later intuitively selected for overexpression to synergistically improve succinic acid production by utilizing abundant NADPH pool mediated by the overexpressed zwf. The LPK7 strains co-expressing mdh alone and both zwf and mdh genes are subjected to fed-batch fermentation to better examine their succinic acid production performances. Strategies of EMC analysis will be useful for further metabolic engineering of M. succiniciproducens and other microorganisms to improve production of succinic acid and other chemicals of interest. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Disorders of branched chain amino acid metabolism.

    Science.gov (United States)

    Manoli, I; Venditti, C P

    2016-11-07

    The three essential branched-chain amino acids (BCAAs), leucine, isoleucine and valine, share the first enzymatic steps in their metabolic pathways, including a reversible transamination followed by an irreversible oxidative decarboxylation to coenzyme-A derivatives. The respective oxidative pathways subsequently diverge and at the final steps yield acetyl- and/or propionyl-CoA that enter the Krebs cycle. Many disorders in these pathways are diagnosed through expanded newborn screening by tandem mass spectrometry. Maple syrup urine disease (MSUD) is the only disorder of the group that is associated with elevated body fluid levels of the BCAAs. Due to the irreversible oxidative decarboxylation step distal enzymatic blocks in the pathways do not result in the accumulation of amino acids, but rather to CoA-activated small carboxylic acids identified by gas chromatography mass spectrometry analysis of urine and are therefore classified as organic acidurias. Disorders in these pathways can present with a neonatal onset severe-, or chronic intermittent- or progressive forms. Metabolic instability and increased morbidity and mortality are shared between inborn errors in the BCAA pathways, while treatment options remain limited, comprised mainly of dietary management and in some cases solid organ transplantation.

  1. Amino Acid Flux from Metabolic Network Benefits Protein Translation: the Role of Resource Availability.

    Science.gov (United States)

    Hu, Xiao-Pan; Yang, Yi; Ma, Bin-Guang

    2015-06-09

    Protein translation is a central step in gene expression and affected by many factors such as codon usage bias, mRNA folding energy and tRNA abundance. Despite intensive previous studies, how metabolic amino acid supply correlates with protein translation efficiency remains unknown. In this work, we estimated the amino acid flux from metabolic network for each protein in Escherichia coli and Saccharomyces cerevisiae by using Flux Balance Analysis. Integrated with the mRNA expression level, protein abundance and ribosome profiling data, we provided a detailed description of the role of amino acid supply in protein translation. Our results showed that amino acid supply positively correlates with translation efficiency and ribosome density. Moreover, with the rank-based regression model, we found that metabolic amino acid supply facilitates ribosome utilization. Based on the fact that the ribosome density change of well-amino-acid-supplied genes is smaller than poorly-amino-acid-supply genes under amino acid starvation, we reached the conclusion that amino acid supply may buffer ribosome density change against amino acid starvation and benefit maintaining a relatively stable translation environment. Our work provided new insights into the connection between metabolic amino acid supply and protein translation process by revealing a new regulation strategy that is dependent on resource availability.

  2. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Science.gov (United States)

    Stibůrková, Blanka; Pavlíková, Markéta; Sokolová, Jitka; Kožich, Viktor

    2014-01-01

    Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  3. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  4. 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

    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......, 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....... Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice....

  5. Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production.

    Directory of Open Access Journals (Sweden)

    Caroline Colijn

    2009-08-01

    Full Text Available Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression, extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB. Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data.

  6. Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid Fatty Acid composition in a muscle type specific manner in sheep.

    Directory of Open Access Journals (Sweden)

    Lei Hou

    Full Text Available We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD and biceps femoris (BF and in the cardiac muscle (ventriculus sinister cordis (VSC of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM or 50% (LOW of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty, twin offspring received a high-carbohydrate-high-fat (HCHF or a moderate-conventional (CONV diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults. The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4 protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced

  7. Effect of metabolic enzyme on organic acids in developing ...

    African Journals Online (AJOL)

    Effect of metabolic enzyme on organic acids in developing 'Dangshansuli' pear leaf. S Sha, J Li, J Wu, S Zhang. Abstract. Changes in the content of citric and malic acids and the activities of enzymes involved in the metabolism of these two organic acids, including citrate synthase (CS), cytoplast aconitase (Cyt-ACO), ...

  8. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Hao, Qin; Jørgensen, Henry

    2011-01-01

    with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited...... increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferatoractivated receptor / target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet...... attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid...

  9. Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; Nielsen, Michael Lynge; Olsson, Lisbeth

    2009-01-01

    factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which...... the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger....

  10. Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice.

    Science.gov (United States)

    Liu, Qian; Shao, Wentao; Zhang, Chunlan; Xu, Cheng; Wang, Qihan; Liu, Hui; Sun, Haidong; Jiang, Zhaoyan; Gu, Aihua

    2017-07-01

    Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Effects of dietary valine:lysine ratio on the performance, amino acid composition of tissues and mRNA expression of genes involved in branched-chain amino acid metabolism of weaned piglets

    Directory of Open Access Journals (Sweden)

    Ye Tong Xu

    2018-01-01

    Full Text Available Objective The goal of this study was to investigate the effects of dietary standard ileal digestible (SID valine:lysine ratios on performance, intestinal morphology, amino acids of liver and muscle, plasma indices and mRNA expression of branched-chain amino acid (BCAA metabolism enzymes. Methods A total of 144 crossbred pigs (Duroc×Landrace×Large White weaned at 28±4 days of age (8.79±0.02 kg body weight were randomly allotted to 1 of 4 diets formulated to provide SID valine:lysine ratios of 50%, 60%, 70%, or 80%. Each diet was fed to 6 pens of pigs with 6 pigs per pen (3 gilts and 3 barrows for 28 days. Results Average daily gain increased quadratically (p<0.05, the villous height of the duodenum, jejunum and ileum increased linearly (p<0.05 as the SID valine:lysine ratio increased. The concentrations of plasma α-keto isovaleric and valine increased linearly (p<0.05, plasma aspartate, asparagine and cysteine decreased (p<0.05 as the SID valine:lysine ratio increased. An increase in SID lysine:valine levels increased mRNA expression levels of mitochondrial BCAA transaminase and branched-chain α-keto acid dehydrogenase in the longissimus dorsi muscle (p<0.05. Conclusion Using a quadratic model, a SID valine:lysine ratio of 68% was shown to maximize the growth of weaned pigs which is slightly higher than the level recommended by the National Research Council [6].

  12. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    Science.gov (United States)

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  13. Metabolic syndrome and the genesis of uric acid stones.

    Science.gov (United States)

    Maalouf, Naim M

    2011-01-01

    Uric acid stones are significantly more common among nephrolithiasis patients with type 2 diabetes, obesity, and/or the metabolic syndrome. The principal metabolic feature responsible for this association is an overly acidic urine, which leads to the precipitation of sparingly soluble uric acid crystals in urine and subsequent development of stones. The unduly acidic urine in uric acid stone formers is caused by a combination of excessive dietary intake of animal proteins and a defect in renal ammoniagenesis and/or excretion that leads to impaired buffering and amplifies the acidic urine caused by an increased acid excretion. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  14. Impact of broiler egg storage on the relative expression of selected blastoderm genes associated with apoptosis, oxidative stress, and fatty acid metabolism

    Science.gov (United States)

    Cool temperature storage of eggs prior to incubation is a frequent practice by commercial broiler hatcheries. However, continued storage beyond 7 days leads to a progressively increase in the rate of early embryonic mortality. In this study, we examined the relative expression of 31 genes associat...

  15. Inborn errors of metabolism revealed by organic acid profile analysis ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence and types of inborn errors of amino acid or organic acid metabolism in a group of high risk Egyptian children with clinical signs and symptoms suggestive of inherited metabolic diseases. Subjects and Methods: 117 (79 males ═ 67.5 % and 38 females ═ 32.5 %) high risk patients with ...

  16. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  17. Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism.

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    Sriram Devanathan

    Full Text Available Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM. While numerous reports have demonstrated increased myocardial fatty acid (FA utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET to estimate myocardial blood flow (MBF and myocardial FA metabolism. Echocardiograms (ECHOs were performed to assess cardiac function. Levels of triglycerides (TG and non-esterified fatty acids (NEFA were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI and decrease in peak early diastolic mitral annular velocity (E' compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

  18. Protein and metabolic engineering for the production of organic acids.

    Science.gov (United States)

    Liu, Jingjing; Li, Jianghua; Shin, Hyun-Dong; Liu, Long; Du, Guocheng; Chen, Jian

    2017-09-01

    Organic acids are natural metabolites of living organisms. They have been widely applied in the food, pharmaceutical, and bio-based materials industries. In recent years, biotechnological routes to organic acids production from renewable raw materials have been regarded as very promising approaches. In this review, we provide an overview of current developments in the production of organic acids using protein and metabolic engineering strategies. The organic acids include propionic acid, pyruvate, itaconic acid, succinic acid, fumaric acid, malic acid and citric acid. We also expect that rapid developments in the fields of systems biology and synthetic biology will accelerate protein and metabolic engineering for microbial organic acid production in the future. Copyright © 2017. Published by Elsevier Ltd.

  19. Alteration of fatty acid metabolism in the liver, adipose tissue, and testis of male mice conceived through assisted reproductive technologies: fatty acid metabolism in ART mice

    Directory of Open Access Journals (Sweden)

    Wang Li-Ya

    2013-01-01

    Full Text Available Abstract Background Lipid metabolism plays important roles in the whole process of pregnancy. Previous studies have demonstrated abnormalities of lipid metabolism in the placentas of pregnancies obtained by assisted reproductive technology (ART. Therefore, we hypothesized that ART micromanipulation may affect lipid metabolism in offspring, and focused on the fatty acid metabolism in ART male offspring in this study. Methods The fatty acid metabolism in the liver, adipose tissue and testis was detected. The comparison between naturally conceived (NC, controlled ovarian hyperstimulation (COH, in vitro fertilization (IVF and intracytoplasmic sperm injection (ICSI mice was made to analyze the effect of ART on offspring. The mice models in this study included two age groups: adult group and old group. The fatty acid composition and the expression of lipid metabolism-related genes were analyzed by GC-MS and qRT-PCR. Results The fatty acid composition in the liver and adipose tissue were significantly altered in ART mice, but no significant difference was found in the testis. In adipose tissue, ART mice showed decreased monounsaturated fatty acids (MUFAs and increased polyunsaturated fatty acids (PUFAs in both adult and old mice, while the alteration of saturated fatty acids (SFAs in the adult disappeared in the old. In liver, the changes were much complex in adult mice, while increased MUFAs and decreased PUFAs were found in ART old mice. The activities of fatty acid metabolism-related enzymes and the expression of lipogenic and lipolytic proteins changed in ART groups, with the adult mice and old mice showing inconsistent alterations. Further analysis indicated that SFAs was closely associated with the alterations of fatty acid metabolism-related enzyme activities and the expression of lipogenic and lipolytic proteins. Furthermore, we also found that the effect of separated ART treatments on fatty acid metabolism varied with different ages and

  20. Production of γ-linolenic acid and stearidonic acid by Synechococcus sp. PCC7002 containing cyanobacterial fatty acid desaturase genes

    Science.gov (United States)

    Dong, Xuewei; He, Qingfang; Peng, Zhenying; Yu, Jinhui; Bian, Fei; Li, Youzhi; Bi, Yuping

    2016-07-01

    Genetic modification is useful for improving the nutritional qualities of cyanobacteria. To increase the total unsaturated fatty acid content, along with the ratio of ω-3/ω-6 fatty acids, genetic engineering can be used to modify fatty acid metabolism. Synechococcus sp. PCC7002, a fast-growing cyanobacterium, does not contain a Δ6 desaturase gene and is therefore unable to synthesize γ-linolenic acid (GLA) and stearidonic acid (SDA), which are important in human health. In this work, we constructed recombinant vectors Syd6D, Syd15D and Syd6Dd15D to express the Δ15 desaturase and Δ6 desaturase genes from Synechocystis PCC6803 in Synechococcus sp. PCC7002, with the aim of expressing polyunsaturated fatty acids. Overexpression of the Δ15 desaturase gene in Synechococcus resulted in 5.4 times greater accumulation of α-linolenic acid compared with the wild-type while Δ6 desaturase gene expression produced both GLA and SDA. Co-expression of the two genes resulted in low-level accumulation of GLA but much larger amounts of SDA, accounting for as much to 11.64% of the total fatty acid content.

  1. Fatty Acids Consumption: The Role Metabolic Aspects Involved in Obesity and Its Associated Disorders

    Directory of Open Access Journals (Sweden)

    Priscila Silva Figueiredo

    2017-10-01

    Full Text Available Obesity and its associated disorders, such as insulin resistance, dyslipidemia, metabolic inflammation, dysbiosis, and non-alcoholic hepatic steatosis, are involved in several molecular and inflammatory mechanisms that alter the metabolism. Food habit changes, such as the quality of fatty acids in the diet, are proposed to treat and prevent these disorders. Some studies demonstrated that saturated fatty acids (SFA are considered detrimental for treating these disorders. A high fat diet rich in palmitic acid, a SFA, is associated with lower insulin sensitivity and it may also increase atherosclerosis parameters. On the other hand, a high intake of eicosapentaenoic (EPA and docosahexaenoic (DHA fatty acids may promote positive effects, especially on triglyceride levels and increased high-density lipoprotein (HDL levels. Moreover, polyunsaturated fatty acids (PUFAs and monounsaturated fatty acids (MUFAs are effective at limiting the hepatic steatosis process through a series of biochemical events, such as reducing the markers of non-alcoholic hepatic steatosis, increasing the gene expression of lipid metabolism, decreasing lipogenic activity, and releasing adiponectin. This current review shows that the consumption of unsaturated fatty acids, MUFA, and PUFA, and especially EPA and DHA, which can be applied as food supplements, may promote effects on glucose and lipid metabolism, as well as on metabolic inflammation, gut microbiota, and hepatic metabolism.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Vaughan Roger A

    2012-10-01

    Full Text Available Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was quantified by measuring extracellular acidification and oxygen consumption rates. Results Omega 3 significantly induced metabolic genes as well as oxidative metabolism (oxygen consumption, glycolytic capacity (extracellular acidification, and metabolic rate compared with control. Both treatments significantly increased mitochondrial content. Conclusion Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control.

  4. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9.

    Science.gov (United States)

    DeBosch, Brian J; Kluth, Oliver; Fujiwara, Hideji; Schürmann, Annette; Moley, Kelle

    2014-08-07

    Excess circulating uric acid, a product of hepatic glycolysis and purine metabolism, often accompanies metabolic syndrome. However, whether hyperuricaemia contributes to the development of metabolic syndrome or is merely a by-product of other processes that cause this disorder has not been resolved. In addition, how uric acid is cleared from the circulation is incompletely understood. Here we present a genetic model of spontaneous, early-onset metabolic syndrome in mice lacking the enterocyte urate transporter Glut9 (encoded by the SLC2A9 gene). Glut9-deficient mice develop impaired enterocyte uric acid transport kinetics, hyperuricaemia, hyperuricosuria, spontaneous hypertension, dyslipidaemia and elevated body fat. Allopurinol, a xanthine oxidase inhibitor, can reverse the hypertension and hypercholesterolaemia. These data provide evidence that hyperuricaemia per se could have deleterious metabolic sequelae. Moreover, these findings suggest that enterocytes may regulate whole-body metabolism, and that enterocyte urate metabolism could potentially be targeted to modulate or prevent metabolic syndrome.

  5. Genome-wide examination of chlorophyll metabolic genes in maize ...

    African Journals Online (AJOL)

    Chlorophyll (Chl) is the key pigment involved in photosynthesis. Analysis of the expression pattern of Chl metabolic genes will contribute to our understanding of photosynthesis. Also, the genes coding for Chl metabolism are ideal targets for revealing the evolution relationships of photosynthetic organisms. In this study, we ...

  6. 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

  7. Correlation of uric acid levels and parameters of metabolic syndrome.

    Science.gov (United States)

    Cibičková, Ľ; Langová, K; Vaverková, H; Kubíčková, V; Karásek, D

    2017-07-18

    Hyperuricemia has been described as associated with the risk of development metabolic syndrome; however the relationship between the uric acid level and particular parameters of metabolic syndrome remained unclear. We performed a cross-sectional study on a cohort of 833 dyslipidemic patients and correlated their levels of uric acid with parameters of insulin resistance, lipid metabolism, C-reactive protein, anthropometric parameters. We also defined patients with hypertriglyceridemic waist phenotype and compered their uric acid levels with those without this phenotype. We found that levels of uric acid are associated with parameters of metabolic syndrome. Specifically, dyslipidemia characteristic for metabolic syndrome (low HDL-cholesterol and high triglycerides) correlates better with uric acid levels than parameters of insulin resistance. Also waist circumference correlates better with uric acid levels than body mass index. Patients with hypertriglyceridemic waist phenotype had higher levels of uric acid when compared with patients without this phenotype. Serum uric acid levels are even in low levels linearly correlated with parameters of metabolic syndrome (better with typical lipid characteristics than with parameters of insulin resistance) and could be associated with higher cardiovascular risk.

  8. Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A

    DEFF Research Database (Denmark)

    Boyles, Abee L; Wilcox, Allen J; Taylor, Jack A

    2009-01-01

    the child had either cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO), and no other major defects. We analyzed 108 SNPs and one insertion in 29 genes involved in folate/one-carbon metabolism and 68 SNPs from 16 genes involved in vitamin A metabolism. Using the Triad Multi......-Marker (TRIMM) approach we performed SNP, gene, chromosomal region, and pathway-wide association tests of child or maternal genetic effects for both CL/P and CPO. We stratified these analyses on maternal intake of folic acid or vitamin A during the periconceptional period. As expected with this high number...

  9. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome.

    Science.gov (United States)

    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle.

  10. 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

    2016-01-04

    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.

  11. BIOCHEMISTRY AND MOLECULAR-BIOLOGY OF GALACTOSIDE TRANSPORT AND METABOLISM IN LACTIC-ACID BACTERIA

    NARCIS (Netherlands)

    POOLMAN, B

    1993-01-01

    Until a few years ago the description of the pathways of transport and metabolism of galactosides in lactic acid bacteria was mainly phenomenological. Different transport and enzymatic activities had been detected but the individual components (proteins, enzymes) were largely unknown and the genes

  12. EFFECTS OF HYDRAZINES ON THE METABOLISM OF CERTAIN AMINES AND AMINO ACIDS.

    Science.gov (United States)

    AMINES, * AMINO ACIDS , *DIAMINE OXIDASE, TOXICITY, METABOLISM, METABOLISM, DIMETHYLHYDRAZINES, GLUTAMIC ACID, ENZYMES, PHARMACOLOGY, TRACER STUDIES, LABELED SUBSTANCES, RESPIRATION, GASTROINTESTINAL SYSTEM, RATS.

  13. EcoCyc: Enyclopedia of Escherichia coli Genes and Metabolism.

    Science.gov (United States)

    Karp, P D; Riley, M; Paley, S M; Pellegrini-Toole, A; Krummenacker, M

    1997-01-01

    The Encyclopedia of Genes and Metabolism (EcoCyc) is a database that combines information about the genome and the intermediary metabolism of Escherichia coli. It describes 2970 genes of E.coli, 547 enzymes encoded by these genes, 702 metabolic reactions that occur in E.coli and the organization of these reactions into 107 metabolic pathways. The EcoCyc graphical user interface allows scientists to query and explore the EcoCyc database using visualization tools such as genomic-map browsers and automatic layouts of metabolic pathways. EcoCyc spans the space from sequence to function to allow scientists to investigate an unusually broad range of questions. EcoCyc can be thought of as both an electronic review article because of its copious references to the primary literature, and as an in silicio model of E.coli metabolism that can be probed and analyzed through computational means.

  14. Human nutrigenomics of gene regulation by dietary fatty acids.

    Science.gov (United States)

    Afman, Lydia A; Müller, Michael

    2012-01-01

    Nutrigenomics employs high-throughput genomics technologies to unravel how nutrients modulate gene and protein expression and ultimately influence cellular and organism metabolism. The most often-applied genomics technique so far is transcriptomics, which allows quantifying genome-wide changes in gene expression of thousands of genes at the same time in one sample. The performance of gene expression quantification requires sufficient high-quality homogenous cellular material, therefore research in healthy volunteers is restricted to biopsies from easy accessible tissues such as subcutaneous adipose tissue, skeletal muscle and intestinal biopsies or even more easily accessible cells such as peripheral blood mononuclear cells from blood. There is now significant evidence that fatty acids, in particular unsaturated fatty acids, exert many of their effects through modulation of gene transcription by regulating the activity of numerous transcription factors, including nuclear receptors such as peroxisome proliferator activated receptors, liver X receptor and sterol regulatory binding proteins. This review evaluates the human nutrigenomics studies performed on dietary fat since the initiation of nutrigenomics research around 10 years ago. Although the number of studies is still limited, all studies clearly suggest that changes in dietary fatty acids intake and composition can have a significant impact on cellular adaptive response capacity by gene transcription changes in humans. This adds important knowledge to our understanding of the strong effects that various fatty acids can have on numerous metabolic and inflammatory pathways, signaling routes and homeostatic control in the cell and ultimately on whole body health. It is important to use and integrate nutrigenomics in all future nutrition studies to build up the necessary framework for evidence-based nutrition in near future. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Acid-Adaptive Genes of Helicobacter pylori

    OpenAIRE

    Wen, Yi; Marcus, Elizabeth A.; Matrubutham, Uday; Gleeson, Martin A.; Scott, David R.; Sachs, George

    2003-01-01

    Helicobacter pylori is the only neutralophile that has been able to colonize the human stomach by using a variety of acid-adaptive mechanisms. One of the adaptive mechanisms is increased buffering due to expression of an acid-activated inner membrane urea channel, UreI, and a neutral pH-optimum intrabacterial urease. To delineate other possible adaptive mechanisms, changes in gene expression in response to acid exposure were examined using genomic microarrays of H. pylori exposed to different...

  16. Systems metabolic engineering strategies for the production of amino acids

    Directory of Open Access Journals (Sweden)

    Qian Ma

    2017-06-01

    Full Text Available Systems metabolic engineering is a multidisciplinary area that integrates systems biology, synthetic biology and evolutionary engineering. It is an efficient approach for strain improvement and process optimization, and has been successfully applied in the microbial production of various chemicals including amino acids. In this review, systems metabolic engineering strategies including pathway-focused approaches, systems biology-based approaches, evolutionary approaches and their applications in two major amino acid producing microorganisms: Corynebacterium glutamicum and Escherichia coli, are summarized.

  17. Systems metabolic engineering strategies for the production of amino acids.

    Science.gov (United States)

    Ma, Qian; Zhang, Quanwei; Xu, Qingyang; Zhang, Chenglin; Li, Yanjun; Fan, Xiaoguang; Xie, Xixian; Chen, Ning

    2017-06-01

    Systems metabolic engineering is a multidisciplinary area that integrates systems biology, synthetic biology and evolutionary engineering. It is an efficient approach for strain improvement and process optimization, and has been successfully applied in the microbial production of various chemicals including amino acids. In this review, systems metabolic engineering strategies including pathway-focused approaches, systems biology-based approaches, evolutionary approaches and their applications in two major amino acid producing microorganisms: Corynebacterium glutamicum and Escherichia coli, are summarized.

  18. Amino Acids as Metabolic Substrates during Cardiac Ischemia

    Science.gov (United States)

    Drake, Kenneth J.; Sidorov, Veniamin Y.; McGuinness, Owen P.; Wasserman, David H.; Wikswo, John P.

    2013-01-01

    The heart is well known as a metabolic omnivore in that it is capable of consuming fatty acids, glucose, ketone bodies, pyruvate, lactate, amino acids and even its own constituent proteins, in order of decreasing preference. The energy from these substrates supports not only mechanical contraction, but also the various transmembrane pumps and transporters required for ionic homeostasis, electrical activity, metabolism and catabolism. Cardiac ischemia – for example, due to compromise of the coronary vasculature or end-stage heart failure – will alter both electrical and metabolic activity. While the effects of myocardial ischemia on electrical propagation and stability have been studied in depth, the effects of ischemia on metabolic substrate preference has not been fully appreciated: oxygen deprivation during ischemia will significantly alter the relative ability of the heart to utilize each of these substrates. Although changes in cardiac metabolism are understood to be an underlying component in almost all cardiac myopathies, the potential contribution of amino acids in maintaining cardiac electrical conductance and stability during ischemia is underappreciated. Despite clear evidence that amino acids exert cardioprotective effects in ischemia and other cardiac disorders, their role in the metabolism of the ischemic heart has yet to be fully elucidated. This review synthesizes the current literature of the metabolic contribution of amino acids during ischemia by analyzing relevant historical and recent research. PMID:23354395

  19. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism.

    Science.gov (United States)

    Germain, Arnaud; Ruppert, David; Levine, Susan M; Hanson, Maureen R

    2017-01-31

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established. In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins. This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361 (P < 0.05), and 35 significantly altered after statistical correction (Q < 0.15). The latter list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients. Pathway analysis points to a few pathways with high impact and therefore potential disturbances in patients, mainly taurine metabolism and glycerophospholipid metabolism, combined with primary bile acid metabolism, as well as glyoxylate and dicarboxylate metabolism and a few other pathways, all involved broadly in fatty acid metabolism. Purines, including ADP and ATP, pyrimidines and several amino acid metabolic pathways were found to be significantly disturbed. Finally, glucose and oxaloacetate were two main metabolites affected that have a major effect on sugar and energy levels. Our work provides a prospective path for diagnosis and understanding of the underlying mechanisms of ME/CFS.

  20. Gene expression in plant lipid metabolism in Arabidopsis seedlings.

    Directory of Open Access Journals (Sweden)

    An-Shan Hsiao

    Full Text Available Events in plant lipid metabolism are important during seedling establishment. As it has not been experimentally verified whether lipid metabolism in 2- and 5-day-old Arabidopsis thaliana seedlings is diurnally-controlled, quantitative real-time PCR analysis was used to investigate the expression of target genes in acyl-lipid transfer, β-oxidation and triacylglycerol (TAG synthesis and hydrolysis in wild-type Arabidopsis WS and Col-0. In both WS and Col-0, ACYL-COA-BINDING PROTEIN3 (ACBP3, DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1 and DGAT3 showed diurnal control in 2- and 5-day-old seedlings. Also, COMATOSE (CTS was diurnally regulated in 2-day-old seedlings and LONG-CHAIN ACYL-COA SYNTHETASE6 (LACS6 in 5-day-old seedlings in both WS and Col-0. Subsequently, the effect of CIRCADIAN CLOCK ASSOCIATED1 (CCA1 and LATE ELONGATED HYPOCOTYL (LHY from the core clock system was examined using the cca1lhy mutant and CCA1-overexpressing (CCA1-OX lines versus wild-type WS and Col-0, respectively. Results revealed differential gene expression in lipid metabolism between 2- and 5-day-old mutant and wild-type WS seedlings, as well as between CCA1-OX and wild-type Col-0. Of the ACBPs, ACBP3 displayed the most significant changes between cca1lhy and WS and between CCA1-OX and Col-0, consistent with previous reports that ACBP3 is greatly affected by light/dark cycling. Evidence of oil body retention in 4- and 5-day-old seedlings of the cca1lhy mutant in comparison to WS indicated the effect of cca1lhy on storage lipid reserve mobilization. Lipid profiling revealed differences in primary lipid metabolism, namely in TAG, fatty acid methyl ester and acyl-CoA contents amongst cca1lhy, CCA1-OX, and wild-type seedlings. Taken together, this study demonstrates that lipid metabolism is subject to diurnal regulation in the early stages of seedling development in Arabidopsis.

  1. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature.

    Directory of Open Access Journals (Sweden)

    Fernando Norambuena

    Full Text Available Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3, with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad-time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher

  2. Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH

    Directory of Open Access Journals (Sweden)

    Benjamin K. Canales

    2017-11-01

    Discussion: Overall, these findings suggest that variants in common genes involved in ammonia metabolism may substantively contribute to basal urine pH regulation. These variations might influence the likelihood of developing disease conditions associated with altered urine pH, such as uric acid or calcium phosphate kidney stones.

  3. Diet-gene interactions between dietary fat intake and common polymorphisms in determining lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Corella, D.

    2009-07-01

    Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolism-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 14C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C) metabolism; the interaction between polyunsaturated fatty acids (PUFA) and the 5G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the -1131T>C in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken. (Author) 31 refs.

  4. Association between serum uric acid level and metabolic syndrome.

    Science.gov (United States)

    Lee, Ju-Mi; Kim, Hyeon Chang; Cho, Hye Min; Oh, Sun Min; Choi, Dong Phil; Suh, Il

    2012-05-01

    Serum uric acid levels have been reported to be associated with a variety of cardiovascular conditions. However, the direct association between uric acid levels and metabolic syndrome remains controversial. Thus, we evaluated the association of serum uric acid levels and metabolic syndrome in a community-based cohort study in Korea. We performed cross-sectional analysis of baseline data of 889 males and 1491 females (aged 38 to 87) who participated in baseline examinations of the Korean Genome and Epidemiology Study: Kanghwa study. Blood samples were collected after at least an 8 hour fast. Uric acid quartiles were defined as follows: Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III Criteria with adjusted waist circumference cutoffs (90 cm for males; 80 cm for females). The association between serum uric acid quartiles and metabolic syndrome was assessed using multivariate logistic regression. The odds ratio for having metabolic syndrome in the highest versus lowest quartiles of serum uric acid levels was 2.67 (95% confidence interval [CI], 1.60 to 4.46) in males and 2.14 (95% CI, 1.50 to 3.05) in females after adjusting for age, smoking, alcohol intake, body mass index, total cholesterol, HbA1c, albumin, γ-glutamyltransferase, blood urea nitrogen, and log C-reactive protein. The number of metabolic abnormalities also increased gradually with increasing serum uric acid levels (adjusted p for trend uric acid levels are positively associated with the presence of metabolic syndrome in Korean males and females.

  5. Ascorbic acid synthesis and metabolism in maize are subject to complex and genotype-dependent feedback regulation during endosperm development.

    Science.gov (United States)

    Sanahuja, Georgina; Farré, Gemma; Bassie, Ludovic; Zhu, Changfu; Christou, Paul; Capell, Teresa

    2013-10-01

    L-ascorbic acid (vitamin C) is an antioxidant and electron donor whose metabolism in plants is under strict feedback control. The factors that influence L-ascorbic acid accumulation in staple crops are only partially understood. One way to gain insight into the regulation of L-ascorbic acid metabolism is to investigate the endogenous pathways in various genetic backgrounds and characterize their interactions with transgenes encoding relevant enzymes. In an initial step, we investigated the developmental profile of L-ascorbic acid accumulation in the endosperm of three diverse maize genotypes and a transgenic line expressing rice dehydroascorbate reductase, which enhances L-ascorbic acid recycling. We determined the transcript levels of all the key genes in the L-ascorbic acid metabolic pathways as well as the specific levels of ascorbic acid and dehydroascorbate. L-ascorbic acid levels were high 20 days after pollination and declined thereafter. We found significant genotype-dependent variations in the transcript levels of some genes, with particular complexity in the ascorbic acid recycling pathway. Our data will help to elucidate the complex mechanisms underlying the regulation of L-ascorbic acid metabolism in plants, particularly the impact of genetic background on the strict regulation of ascorbic acid metabolism in endosperm cells. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Production of amino acids - Genetic and metabolic engineering approaches.

    Science.gov (United States)

    Lee, Jin-Ho; Wendisch, Volker F

    2017-12-01

    The biotechnological production of amino acids occurs at the million-ton scale and annually about 6milliontons of l-glutamate and l-lysine are produced by Escherichia coli and Corynebacterium glutamicum strains. l-glutamate and l-lysine production from starch hydrolysates and molasses is very efficient and access to alternative carbon sources and new products has been enabled by metabolic engineering. This review focusses on genetic and metabolic engineering of amino acid producing strains. In particular, rational approaches involving modulation of transcriptional regulators, regulons, and attenuators will be discussed. To address current limitations of metabolic engineering, this article gives insights on recent systems metabolic engineering approaches based on functional tools and method such as genome reduction, amino acid sensors based on transcriptional regulators and riboswitches, CRISPR interference, small regulatory RNAs, DNA scaffolding, and optogenetic control, and discusses future prospects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Specific fatty acids as metabolic modulators in the dairy cow

    Directory of Open Access Journals (Sweden)

    J.A.A. Pires

    2008-07-01

    Full Text Available This review summarizes recent developments on the utilization of specific fatty acids to modulate bovine energy metabolism, with emphasis on the periparturient dairy cow. A number of experiments have assessed the effects of polyunsaturated fatty acids on bovine hepatic energy metabolism using in vitro and in vivo models. Treatment of hepatocytes with specific fatty acids altered energy metabolism in vitro. For example, linolenic acid seemed to decrease hepatocyte triacylglycerol accumulation. This effect was confirmed in vivo, using parenteral infusions of emulsions derived from different fat sources to feed-restricted non-lactating cows. Additionally, polyunsaturated fatty acids can increase whole body response to insulin, potentially enhancing antilipolytic effects of insulin and muscle protein anabolism in the bovine. There is limited literature on the effects of feeding fat sources rich in omega-3 polyunsaturated fatty acids, such as fish oil and linseed oil, on metabolism of periparturient dairy cows. Available research has yielded conflicting results which need further clarification. On the other hand, specific isomers of conjugated linoleic acid consistently induce milk fat depression and are able to decrease energy export in milk by periparturient dairy cows. Nonetheless, research is still needed to assess whether these effects will ultimately benefit productivity and health status of periparturient dairy cows. Limitations of available methods to protect fatty acids from ruminal biohydrogenation are also addressed.

  8. Engineering metabolic highways in Lactococci and other lactic acid bacteria

    NARCIS (Netherlands)

    Vos, de W.M.; Hugenholtz, J.

    2004-01-01

    Lactic acid bacteria (LAB) are widely used in industrial food fermentations and are receiving increased attention for use as cell factories for the production of food and pharmaceutical products. Glycolytic conversion of sugars into lactic acid is the main metabolic highway in these Gram-positive

  9. Salicylic Acid Alters Antioxidant and Phenolics Metabolism in ...

    African Journals Online (AJOL)

    Background: Salicylic acid (SA) acts as a potential non-enzymatic antioxidant and a plant growth regulator, which plays a major role in regulating various plant physiological mechanisms. The effects of salicylic acid (SA; 0.05 mM) on physiological parameters, antioxidative capacity and phenolic metabolism, lignin, alkaloid ...

  10. Serum uric acid and metabolic syndrome in Taiwanese adults.

    Science.gov (United States)

    Liu, Pei-Wen; Chang, Tsui-Yen; Chen, Jong-Dar

    2010-06-01

    A positive association between serum uric acid and metabolic syndrome has been reported, but little information is available about the association between serum uric acid and metabolic syndrome in Taiwanese adults. The purpose of this study was to investigate the association between serum uric acid levels and metabolic syndrome in Taiwanese adults. We performed a cross-sectional study of 2085 men and 1557 women. All of the participants underwent a health screening during the period from January 2005 to December 2005 at a health center of the Shin Kong Wu Ho-Su Memorial Hospital. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The results showed that hyperuricemia was significantly associated with increased risk for hypertriglyceridemia, low high-density lipoprotein cholesterol level, and high blood pressure in men and women. The risk of metabolic syndrome was significantly higher in the fourth quartile than in the first quartile of uric acid level in men (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.06-2.14) and women (OR, 2.33; 95% CI, 1.39-3.93). In addition, uric acid level was inversely associated with hyperglycemia in men. The ORs of hyperglycemia for the second, third, and fourth quartile of uric acid were 0.69 (95% CI, 0.46-1.03), 0.55 (95% CI, 0.37-0.83), and 0.45 (95% CI, 0.29-0.69), respectively, compared with the lowest quartile of uric acid. The results demonstrate that there is a positive association between serum uric acid levels and metabolic syndrome and an inverse association between uric acid and fasting plasma glucose in Taiwanese adults. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Pathophysiological aspect of metabolic acid-base disorders

    Directory of Open Access Journals (Sweden)

    Nešović-Ostojić Jelena

    2016-01-01

    Full Text Available Maintaing the arterial pH values (in normal range of 7,35-7,45 is one of the main principles of homeostasis. Regulatory responses, including chemical buffering (extracellular, intracellular, sceletal, the regulation of pCO2 by the respiratory system, and the regulation of [HCO3-] by the kidneys, act in concert to maintain normal arterial pH value. The main extracellular chemical buffer is bicarbonate-carbonic acid buffer system. The kidneys contribute to the regulation of hydrogen (and bicarbonate in body fluids in two ways. Proximal tubules are important in bicarbonate reabsorption and distal tubules excrete hydrogen ion (as ammonium ion or titratable acid. There are four simple acid-base disorders: metabolic acidosis and metabolic alkalosis; respiratory acidosis and respiratory alkalosis. Metabolic acidosis can occur because of an increase in endogenous acid production (such as lactate and ketoacids, loss of bicarbonate (as in diarrhea, or accumulation of endogenous acids (as in renal failure. Metabolic acidosis can also be with high and normal (hyperchloremic metabolic acidosis anion gap. Renal tubular acidosis (RTA is a form of hyperchloremic metabolic acidosis which occurs when the renal damage primarily affects tubular function. The main problem in distal RTA is reduced H+ excretion in distal tubule. Type 2 RTA is also called proximal RTA because the main problem is greatly impaired reabsorption of bicarbonate in proximal tubule. Impaired cation exchange in distal tubule is the main problem in RTA type 4. Metabolic alkalosis occurs as a result of net gain of [HCO3-] or loss of nonvolatile acid from extracellular fluids. Metabolic alkalosis can be associated with reduced or increased extracellular volume.

  12. Induction of PEP carboxylase and crassulacean acid metabolism by gibberellic acid in Mesembryanthemum crystallinum.

    Science.gov (United States)

    Guralnick, L J; Ku, M S; Edwards, G E; Strand, D; Hockema, B; Earnest, J

    2001-02-01

    The induction of Crassulacean acid metabolism in M:esembryanthemum crystallinum was investigated in response to foliar application of gibberellic acid (GA). After 5 weeks of treatment, GA-treated plants showed 1.7- to almost a 4-fold increase of phosphoenolpyruvate carboxylase (PEPcase) activity with a concomitant increase in acid metabolism when compared to control plants. Immunoblot analysis indicated an increase in the PEPcase protein similar to that of salt treatment while Rubisco did not show a similar rise. The results indicate that exogenously applied GA accelerates plant developmental expression of PEPcase and Crassulacean acid metabolism in M: crystallinum.

  13. Metabolic Genes within Cyanophage Genomes: Implications for Diversity and Evolution

    Directory of Open Access Journals (Sweden)

    E-Bin Gao

    2016-09-01

    Full Text Available Cyanophages, a group of viruses specifically infecting cyanobacteria, are genetically diverse and extensively abundant in water environments. As a result of selective pressure, cyanophages often acquire a range of metabolic genes from host genomes. The host-derived genes make a significant contribution to the ecological success of cyanophages. In this review, we summarize the host-derived metabolic genes, as well as their origin and roles in cyanophage evolution and important host metabolic pathways, such as the light-dependent reactions of photosynthesis, the pentose phosphate pathway, nutrient acquisition and nucleotide biosynthesis. We also discuss the suitability of the host-derived metabolic genes as potential diagnostic markers for the detection of genetic diversity of cyanophages in natural environments.

  14. Acetobacter pasteurianus metabolic change induced by initial acetic acid to adapt to acetic acid fermentation conditions.

    Science.gov (United States)

    Zheng, Yu; Zhang, Renkuan; Yin, Haisong; Bai, Xiaolei; Chang, Yangang; Xia, Menglei; Wang, Min

    2017-09-01

    Initial acetic acid can improve the ethanol oxidation rate of acetic acid bacteria for acetic acid fermentation. In this work, Acetobacter pasteurianus was cultured in ethanol-free medium, and energy production was found to increase by 150% through glucose consumption induced by initial acetic acid. However, oxidation of ethanol, instead of glucose, became the main energy production pathway when upon culturing ethanol containing medium. Proteome assay was used to analyze the metabolism change induced by initial acetic acid, which provided insight into carbon metabolic and energy regulation of A. pasteurianus to adapt to acetic acid fermentation conditions. Results were further confirmed by quantitative real-time PCR. In summary, decreased intracellular ATP as a result of initial acetic acid inhibition improved the energy metabolism to produce more energy and thus adapt to the acetic acid fermentation conditions. A. pasteurianus upregulated the expression of enzymes related to TCA and ethanol oxidation to improve the energy metabolism pathway upon the addition of initial acetic acid. However, enzymes involved in the pentose phosphate pathway, the main pathway of glucose metabolism, were downregulated to induce a change in carbon metabolism. Additionally, the enhancement of alcohol dehydrogenase expression promoted ethanol oxidation and strengthened the acetification rate, thereby producing a strong proton motive force that was necessary for energy production and cell tolerance to acetic acid.

  15. Metabolic engineering of chloroplasts for artemisinic acid ...

    Indian Academy of Sciences (India)

    biosynthesis and impact on plant growth. BHAWNA SAXENA, MAYAVAN SUBRAMANIYAN, KARAN ... Supplementary table 1. 13C NMR chemical shifts of artemisinic acid and structure of artemisinic acid. Atom num- bers are referred to figure 3A-B. Carbon number. Chemical shift (ppm). C1. 29. C2. 37. C3. 42. C4. 26.5. C5.

  16. KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism

    Directory of Open Access Journals (Sweden)

    Erhu Zhao

    2016-01-01

    Full Text Available The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here, we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in intracellular amino acid levels. Examination of the serine-glycine synthesis pathway reveals that KDM4C epigenetically activates the pathway genes under steady-state and serine deprivation conditions by removing the repressive histone modification H3 lysine 9 (H3K9 trimethylation. This action of KDM4C requires ATF4, a transcriptional master regulator of amino acid metabolism and stress responses. KDM4C activates ATF4 transcription and interacts with ATF4 to target serine pathway genes for transcriptional activation. We further present evidence for KDM4C in transcriptional coordination of amino acid metabolism and cell proliferation. These findings suggest a molecular mechanism linking KDM4C-mediated H3K9 demethylation and ATF4-mediated transactivation in reprogramming amino acid metabolism for cancer cell proliferation.

  17. Characterization of the Shewanella oneidensis Fur gene: roles in iron and acid tolerance response

    OpenAIRE

    Wu Liyou; Luo Feng; Harris Daniel P; Yang Yunfeng; Parsons Andrea B; Palumbo Anthony V; Zhou Jizhong

    2008-01-01

    Abstract Background Iron homeostasis is a key metabolism for most organisms. In many bacterial species, coordinate regulation of iron homeostasis depends on the protein product of a Fur gene. Fur also plays roles in virulence, acid tolerance, redox-stress responses, flagella chemotaxis and metabolic pathways. Results We conducted physiological and transcriptomic studies to characterize Fur in Shewanella oneidensis, with regard to its roles in iron and acid tolerance response. A S. oneidensisf...

  18. Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.

    Science.gov (United States)

    Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J

    2017-01-01

    Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia. We evaluated 103 patients less than 40 years of age, from a low-income population, and without history of cardiovascular disease, in all of them the presence of metabolic syndrome was assessed in accordance with the International Diabetes Federation criteria. In all patients, fasting serum uric acid levels were measured; hyperuricaemia was defined as serum uric acid values 6.5 mg/dl in men and 5.1 mg/dl in women. Statistical analysis was performed with odds ratio. 83 of our patients (80.5%) suffered metabolic syndrome, the odds ratio for the presence of metabolic syndrome in patients with hyperuricaemia was 5.1 (p=0.002, I.C 1.8- 14.5). When patients were evaluated by gender a significantly association between hyperuricaemia and metabolic syndrome was found in women (odds ratio 3.6, p=0.048, C.I. 1.0-12.9), and men (odds ratio 10.2, p= 0.015, IC 1.5-13.2). When uric acid was correlated with the components of metabolic syndrome, we only found a positive correlation with waist circumference (r=0.483). Our results showed a significant association between hyperuricemia and metabolic syndrome in low-income young adults in Mexico. DR is associated with estimated risk of CVD in type 2 diabetic patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Metabollic Engineering of Saccharomyces Cereviae a,omi acid metabolism for production of products of industrial interest

    DEFF Research Database (Denmark)

    Chen, Xiao

    Saccharomyces cerevisiae is widely used in microbial production of chemicals, metabolites and proteins, mainly because genetic manipulation of S. cerevisiae is relatively easy and experiences from its wide application in the existing industrial fermentations directly benefit new S. cerevisiae......, by simultaneous overexpression of biosynthetic genes ILV2, ILV3, and ILV5 in valine metabolism in S. cerevisiae, the isobutanol yield was improved from 0.16 to 0.97 mg per g glucose in anaerobic fermentation in mineral medium. Isobutanol yield was further improved by two times by the additional overexpression......-based processes. This study has focused on metabolic engineering of the amino acid metabolism in S. cerevisiae for production of two types of chemicals of industrial interest. The first chemical is δ-(L-α-aminoadipyl)–L-cysteinyl–D-valine (LLD-ACV). ACV belongs to non-ribosomal peptides (NRPs), which...

  20. Metabolic modeling of Rosmarinic acid biosynthetic pathway

    OpenAIRE

    Sundaram, Shanthy; Tripathi, Ashutosh; Gupta, Deepak K

    2010-01-01

    Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4‐dihydroxyphenyllacticacid. It is commonly found in Coleus blumei, Salvia officinalis, Melissa officinalis and Rosmarinus officinalis. The biosynthesis of RA starts with precursor molecules L‐phenylalanine and L‐tyrosine. Simulation of RA biosynthetic pathway was done using Gepasi Software, includes the reaction kinetics of each step of the pathway and different integration methods such as Euler's method. Optimization of the significant...

  1. Biobased organic acids production by metabolically engineered microorganisms

    DEFF Research Database (Denmark)

    Chen, Yun; Nielsen, Jens

    2016-01-01

    Bio-based production of organic acids via microbial fermentation has been traditionally used in food industry. With the recent desire to develop more sustainable bioprocesses for production of fuels, chemicals and materials, the market for microbial production of organic acids has been further...... expanded as organic acids constitute a key group among top building block chemicals that can be produced from renewable resources. Here we review the current status for production of citric acid and lactic acid, and we highlight the use of modern metabolic engineering technologies to develop high...... performance microbes for production of succinic acid and 3-hydroxypropionic acid. Also, the key limitations and challenges in microbial organic acids production are discussed...

  2. Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats.

    Science.gov (United States)

    Khaire, Amrita; Rathod, Richa; Kale, Anvita; Joshi, Sadhana

    2015-08-01

    Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (pacid (DHA) (pOmega-3 fatty acid supplementation to this group normalized cholesterol but not mRNA levels of ACC-1 and CPT-1. Vitamin B12 supplementation normalized the levels cholesterol to that of control but increased plasma triglyceride (pomega-3 fatty acid normalized triglyceride and mRNA levels of all the above genes. Prenatal and postnatal vitamin B12 and omega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Integration of metabolic networks and gene expression in virtual reality.

    Science.gov (United States)

    Yang, Yuting; Engin, Levent; Wurtele, Eve Syrkin; Cruz-Neira, Carolina; Dickerson, Julie A

    2005-09-15

    Metabolic networks combine metabolism and regulation. These complex networks are difficult to understand and visualize due to the amount and diverse types of information that need to be represented. For example, pathway information gives indications of interactions. Experimental data, such as transcriptomics, proteomics and metabolomics data, give snapshots of the system state. Stereoscopic virtual environments provide a true three-dimensional representation of metabolic networks, which can be intuitively manipulated, and may help to manage the data complexity. MetNet3D, a 3D virtual reality system, allows a user to explore gene expression and metabolic pathway data simultaneously. Normalized gene expression data are processed in R and visualized as a 3D plot. Users can find a particular gene of interest or a cluster of genes that behave similarly and see how these genes function in metabolic networks from MetNetDB, a database of Arabidopsis metabolic networks, using animated network graphs. Interactive virtual reality, with its enhanced ability to display more information, makes such integration more effective by abstracting key relationships. MetNet3D and some sample datasets are available at http://www.vrac.iastate.edu/research/sites/metnet/Download/Download.htm. Color snapshots and movies are available at http://www.vrac.iastate.edu/research/sites/metnet/Bioinformatics/SupplementaryInformation.htm.

  4. Fatty acids from diet and microbiota regulate energy metabolism

    OpenAIRE

    Joe Alcock; Lin, Henry C.

    2015-01-01

    A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly ...

  5. Metabolic engineering of Yarrowia lipolytica for itaconic acid production.

    Science.gov (United States)

    Blazeck, John; Hill, Andrew; Jamoussi, Mariam; Pan, Anny; Miller, Jarrett; Alper, Hal S

    2015-11-01

    Itaconic acid is a naturally produced organic acid with diverse applications as a replacement for petroleum derived products. However, its industrial viability as a bio-replacement has been restricted due to limitations with native producers. In this light, Yarrowia lipolytica is an excellent potential candidate for itaconic acid production due to its innate capacity to accumulate citric acid cycle intermediates and tolerance to lower pH. Here, we demonstrate the capacity to produce itaconic acid in Y. lipolytica through heterologous expression of the itaconic acid synthesis enzyme, resulting in an initial titer of 33 mg/L. Further optimizations of this strain via metabolic pathway engineering, enzyme localization, and media optimization strategies enabled 4.6g/L of itaconic acid to be produced in bioreactors, representing a 140-fold improvement over initial titer. Moreover, these fermentation conditions did not require additional nutrient supplementation and utilized a low pH condition that enabled the acid form of itaconic acid to be produced. Overall yields (0.058 g/g yield from glucose) and maximum productivity of 0.045 g/L/h still provide areas for future strain improvement. Nevertheless, this work demonstrates that Y. lipolytica has the potential to serve as an industrially relevant platform for itaconic acid production. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  6. Can valproic acid be an inducer of clozapine metabolism?

    Science.gov (United States)

    Diaz, Francisco J.; Eap, Chin B.; Ansermot, Nicolas; Crettol, Severine; Spina, Edoardo; de Leon, Jose

    2014-01-01

    Introduction Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that 1) VPA is a net inducer of clozapine metabolism, and 2) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. Methods After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. Results VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14% to 39%) after controlling for confounding variables including smoking (35% lower, 28% to 56%). Discussion Prospective studies are needed to definitively establish that VPA may 1) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and 2) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism. PMID:24764199

  7. Salivary uric acid as a noninvasive biomarker of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Soukup Maria

    2012-04-01

    Full Text Available Abstract Background Elevated serum uric acid is associated with obesity, hypertension and metabolic syndrome. Because a linear relationship exists between serum and salivary uric acid (SUA concentration, saliva testing may be a useful noninvasive approach for monitoring cardiometabolic risk. The goal of this pilot study was to determine if SUA is increased in patients with metabolic syndrome and to investigate correlations between SUA and individual cardiometabolic risk factors. Findings Volunteers between the ages of 18 and 65 without conditions known to affect serum uric acid levels were recruited. Height, weight, blood pressure and waist circumference were measured and a full lipid panel along with fasting blood glucose was obtained. Saliva samples were collected and uric acid levels were determined. 78 volunteers, 35% of whom had metabolic syndrome, completed the study. SUA was significantly elevated in patients with metabolic syndrome (p=.002. The incidence of metabolic syndrome in the 4th quartile for SUA was 67% compared to 25% in quartiles1-3 combined. Significant correlations were seen between SUA and systolic blood pressure (r=.440, p=.000, diastolic blood pressure ( r=.304, p=.007, waist circumference (r=.332, p=.003, BMI ( r=.269, p=.018, fasting blood glucose ( r=.341, p=.002, triglycerides (r=.410, p=.000, HDL ( r=.237, p=.036 and the number of cardiometabolic risk factors present (r=0.257, p=.023. Conclusions These results suggest that SUA may be a useful biomarker for noninvasive monitoring of cardiometabolic risk. Larger studies are needed to validate this approach.

  8. Salivary uric acid as a noninvasive biomarker of metabolic syndrome.

    Science.gov (United States)

    Soukup, Maria; Biesiada, Izabela; Henderson, Aaron; Idowu, Benmichael; Rodeback, Derek; Ridpath, Lance; Bridges, Edward G; Nazar, Andrea M; Bridges, Kristie Grove

    2012-04-19

    Elevated serum uric acid is associated with obesity, hypertension and metabolic syndrome. Because a linear relationship exists between serum and salivary uric acid (SUA) concentration, saliva testing may be a useful noninvasive approach for monitoring cardiometabolic risk. The goal of this pilot study was to determine if SUA is increased in patients with metabolic syndrome and to investigate correlations between SUA and individual cardiometabolic risk factors. Volunteers between the ages of 18 and 65 without conditions known to affect serum uric acid levels were recruited. Height, weight, blood pressure and waist circumference were measured and a full lipid panel along with fasting blood glucose was obtained. Saliva samples were collected and uric acid levels were determined. 78 volunteers, 35% of whom had metabolic syndrome, completed the study. SUA was significantly elevated in patients with metabolic syndrome (p=.002). The incidence of metabolic syndrome in the 4th quartile for SUA was 67% compared to 25% in quartiles1-3 combined. Significant correlations were seen between SUA and systolic blood pressure (r=.440, p=.000), diastolic blood pressure ( r=.304, p=.007), waist circumference (r=.332, p=.003), BMI ( r=.269, p=.018), fasting blood glucose ( r=.341, p=.002), triglycerides (r=.410, p=.000), HDL ( r=.237, p=.036) and the number of cardiometabolic risk factors present (r=0.257, p=.023). These results suggest that SUA may be a useful biomarker for noninvasive monitoring of cardiometabolic risk. Larger studies are needed to validate this approach.

  9. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  10. Metabolic engineering of Escherichia coli for biosynthesis of hyaluronic acid.

    Science.gov (United States)

    Yu, Huimin; Stephanopoulos, Gregory

    2008-01-01

    Engineering of hyaluronic acid (HA) biosynthetic pathway in recombinant Escherichia coli as production host is reported in this work. A hyaluronic acid synthase (HAS) gene, sphasA, from Sreptococcus pyogenes with the start codon gtg to atg mutant, was expressed in recombinant E. coli with or without the genes ugd, galF and glmU, which are analogs of hasB, hasC and hasD from Streptococcus, respectively, encoding UDP-glucose 6-dehygrogenase, Glucose-1-P uridyltransferase, and N-acetyl glucosamine uridyltransferase enzymes in the HA biosynthetic pathway. The single, double and triple organized artificial operons of sphasA, ugd, galF and glmU were designed and constructed using the inducible plasmid backbone of pMBAD. Only the triple expression recombinant, Top10/pMBAD-spABC, generated a relatively high titer of HA (approximately 48 mg/l at 48 h), indicating that both of the enzymes encoded by ugd and galF are essential for HA biosynthesis. A new gene of ssehasA with identical protein sequence of seHAS from Streptococcus equisimilis, was artificially synthesized after substituting all of the rare codons in the natural sehasA. The HA titer at 24 h flask culture increased to approximately 190 mg/l in sseAB and 160 mg/l in sseABC, respectively. Sorbitol could be used as another carbon source for HA accumulation, and the metabolic pathway for HA synthesis in a recombinant E. coli was presented. The concentration of Mg(2+) cofactor of HA synthase was optimized and a cell growth inhibition phenomenon was observed during HA accumulation. Molecular weight (MW) measurements revealed that the mean MW of HA produced from the recombinant E. coli under different conditions ranges from approximately 3.5x10(5) to 1.9x10(6)Da, indicating that the recombinant E. coli can be used as a potential host candidate for industrial production of HA.

  11. Metabolic modeling of Rosmarinic acid biosynthetic pathway

    Science.gov (United States)

    Sundaram, Shanthy; Tripathi, Ashutosh; Gupta, Deepak K

    2010-01-01

    Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4‐dihydroxyphenyllacticacid. It is commonly found in Coleus blumei, Salvia officinalis, Melissa officinalis and Rosmarinus officinalis. The biosynthesis of RA starts with precursor molecules L‐phenylalanine and L‐tyrosine. Simulation of RA biosynthetic pathway was done using Gepasi Software, includes the reaction kinetics of each step of the pathway and different integration methods such as Euler's method. Optimization of the significant parameters responsible for RA biosynthesis was carried out. As the goal of the work was to increase the productivity of i.e. to maximize the concentration of the RA, the final concentration of RA ([RA]t) was selected as an objective function and selected initial concentration of the Caffeoyl‐3’‐4’hydroxyphenyllactic acid (3’C4HPLA) as parameter constraint and varied its initial concentration as: 0≤ [3’C4HPLA]i ≤ 0.025. Several optimization methods such as Simulated annealing, Evolutionary algorithms and Genetic algorithms were used to optimize the objective function. After optimization the final concentration of RA was slightly higher (4.566132e‐002 mM) than before optimization (4.047119e‐ 002 mM). On the basis of results obtained, it is clear that 4‐hydroxyphenyllactic acid and 3’C4HPLA play major role in the high productivity of the RA. PMID:21364781

  12. Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes.

    Science.gov (United States)

    Le Lay, S; Krief, S; Farnier, C; Lefrère, I; Le Liepvre, X; Bazin, R; Ferré, P; Dugail, I

    2001-05-18

    Enlarged fat cells exhibit modified metabolic capacities, which could be involved in the metabolic complications of obesity at the whole body level. We show here that sterol regulatory element-binding protein 2 (SREBP-2) and its target genes are induced in the adipose tissue of several models of rodent obesity, suggesting cholesterol imbalance in enlarged adipocytes. Within a particular fat pad, larger adipocytes have reduced membrane cholesterol concentrations compared with smaller fat cells, demonstrating that altered cholesterol distribution is characteristic of adipocyte hypertrophy per se. We show that treatment with methyl-beta-cyclodextrin, which mimics the membrane cholesterol reduction of hypertrophied adipocytes, induces insulin resistance. We also produced cholesterol depletion by mevastatin treatment, which activates SREBP-2 and its target genes. The analysis of 40 adipocyte genes showed that the response to cholesterol depletion implicated genes involved in cholesterol traffic (caveolin 2, scavenger receptor BI, and ATP binding cassette 1 genes) but also adipocyte-derived secretion products (tumor necrosis factor alpha, angiotensinogen, and interleukin-6) and proteins involved in energy metabolism (fatty acid synthase, GLUT 4, and UCP3). These data demonstrate that altering cholesterol balance profoundly modifies adipocyte metabolism in a way resembling that seen in hypertrophied fat cells from obese rodents or humans. This is the first evidence that intracellular cholesterol might serve as a link between fat cell size and adipocyte metabolic activity.

  13. Enhancement of 3-hydroxypropionic acid production from glycerol by using a metabolic toggle switch.

    Science.gov (United States)

    Tsuruno, Keigo; Honjo, Hiroshi; Hanai, Taizo

    2015-10-05

    3-hydroxypropionic acid (3-HP) is an important platform for the production of C3 chemicals, including acrylic acid, methyl acrylate, and acrylamide. Microbial production of 3-HP is mainly due to glycerol metabolism. In this study, in order to improve microbial 3-HP production, we applied a metabolic toggle switch for controlling the glycerol metabolism to redirect the excess metabolic flux of central metabolic pathway toward an exogenous 3-HP producing pathway in Escherichia coli. The metabolic toggle switch enables conditional repression of the expression of a target gene during the fermentation. We individually performed conditional repression of glpK, tpiA, and gapA, which are involved in glycerol metabolism. The conditional repression of glpK and tpiA was not effective for 3-HP production under our experimental conditions. However, gapA conditional repression contributed to improve 3-HP production (titer, 54.2 ± 1.5 mM; yield, 32.1 ± 1.3 %) compared with that for the wild type strain. Additional deletion of endogenous yqhD, which is responsible for the production of a major byproduct, 1,3-propandiol, further increased 3-HP production (titer, 67.3 ± 2.1 mM; yield, 51.5 ± 3.2 %). The titer and yield were 80 and 94 % higher than those of the wild type strain, respectively. The obtained 3-HP yield from glycerol is comparable with the highest yield ever reported for microbial 3-HP production using glycerol as a sole carbon source. The measurement of intracellular metabolites showed the metabolic toggle switch successfully controlled the metabolic flux. The conditional repression of gapA by using the metabolic toggle switch combined with deletion of endogeneous yqhD increased 3-HP production approximately twofold from glycerol. This result indicates the metabolic toggle switch can be applied in various bio-production using diverse substrates.

  14. Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters.

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    Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen

    2017-02-01

    The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI.

  15. Expression of fatty acid synthesis genes and fatty acid accumulation in haematococcus pluvialis under different stressors

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    Lei Anping

    2012-03-01

    Full Text Available Abstract Background Biofuel has been the focus of intensive global research over the past few years. The development of 4th generation biofuel production (algae-to-biofuels based on metabolic engineering of algae is still in its infancy, one of the main barriers is our lacking of understanding of microalgal growth, metabolism and biofuel production. Although fatty acid (FA biosynthesis pathway genes have been all cloned and biosynthesis pathway was built up in some higher plants, the molecular mechanism for its regulation in microalgae is far away from elucidation. Results We cloned main key genes for FA biosynthesis in Haematococcus pluvialis, a green microalga as a potential biodiesel feedstock, and investigated the correlations between their expression alternation and FA composition and content detected by GC-MS under different stress treatments, such as nitrogen depletion, salinity, high or low temperature. Our results showed that high temperature, high salinity, and nitrogen depletion treatments played significant roles in promoting microalgal FA synthesis, while FA qualities were not changed much. Correlation analysis showed that acyl carrier protein (ACP, 3-ketoacyl-ACP-synthase (KAS, and acyl-ACP thioesterase (FATA gene expression had significant correlations with monounsaturated FA (MUFA synthesis and polyunsaturated FA (PUFA synthesis. Conclusions We proposed that ACP, KAS, and FATA in H. pluvialis may play an important role in FA synthesis and may be rate limiting genes, which probably could be modified for the further study of metabolic engineering to improve microalgal biofuel quality and production.

  16. Metabolic reprogramming of hydrogenosomal amino acids in Trichomonas vaginalis under glucose restriction.

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    Huang, Kuo-Yang; Ong, Seow-Chin; Wu, Chih-Ching; Hsu, Chia-Wei; Lin, Hsin-Chung; Fang, Yi-Kai; Cheng, Wei-Hung; Huang, Po-Jung; Chiu, Cheng-Hsun; Tang, Petrus

    2017-11-21

    Glucose is the major energy source that is converted to pyruvate for ATP generation in the trichomonad hydrogenosome. Under glucose restriction (GR), the regulation of amino acids metabolism is crucial for trichomonad growth and survival. RNA-sequencing (RNA-seq) analysis has been used to identify differentially expressed genes in Trichomonas vaginalis under GR, leading to significant advances in understanding adaptive responses of amino acid metabolism to GR. However, the levels of amino acid metabolites modulated by GR are unknown in T. vaginalis. Herein, we describe a comprehensive metabolomic analysis of amino acid metabolites in the hydrogenosome using liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry (LC-FT MS). The relative abundance of 17 hydrogenosomal amino acids was analyzed under GR and high-glucose (HG) conditions. Levels of most amino acids were higher in GR culture. Arginine was not detectable in either HG or GR cultures; however, its metabolic end-product proline was slightly increased under GR, suggesting that the arginine dihydrolase pathway was more activated by GR. Additionally, methionine catabolism was less stimulated under GR because of greater methionine accumulation. Furthermore, branched chain amino acids (BCAA), including leucine, isoleucine and valine, as well as phenylalanine and alanine, markedly accumulated under GR, indicating that glutamate-related metabolic pathways were remarkably enhanced in this setting. Our metabolomic analysis combined with previous RNA-seq data confirm the existence of several amino acid metabolic pathways in the hydrogenosome and highlight their potentially important roles in T. vaginalis under glucose deprivation. Copyright © 2017. Published by Elsevier B.V.

  17. Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

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    Helen J Renaud

    Full Text Available The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age. The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched, Day 10-Day 20 (pre-weaning-enriched, and Day 25-Day 60 (adolescence/adulthood-enriched. Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty

  18. Dataset of the human homologues and orthologues of lipid-metabolic genes identified as DAF-16 targets their roles in lipid and energy metabolism

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    Lavender Yuen-Nam Fan

    2017-04-01

    Full Text Available The data presented in this article are related to the review article entitled ‘Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis’ (Saavedra-Garcia et al., 2017 [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C. elegans. This dataset has not been uploaded to a public repository yet.

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

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    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. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. 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. 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.

  20. N-3 fatty acids, neuronal activity and energy metabolism in the brain

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    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  1. The response of gene expression associated with lipid metabolism, fat deposition and fatty acid profile in the longissimus dorsi muscle of Gannan yaks to different energy levels of diets.

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    Chao Yang

    Full Text Available The energy available from the diet, which affects fat deposition in vivo, is a major factor in the expression of genes regulating fat deposition in the longissimus dorsi muscle. Providing high-energy diets to yaks might increase intramuscular fat deposition and fatty acid concentrations under a traditional grazing system in cold seasons. A total of fifteen adult castrated male yaks with an initial body weight 274.3 ± 3.14 kg were analyzed for intramuscular adipose deposition and fatty acid composition. The animals were divided into three groups and fed low-energy (LE: 5.5 MJ/kg, medium-energy (ME: 6.2 MJ/kg and high-energy (HE: 6.9 MJ/kg diets, respectively. All animals were fed ad libitum twice daily at 08:00-09:00 am and 17:00-18:00 pm and with free access to water for 74 days, including a 14-d period to adapt to the diets and the environment. Intramuscular fat (IMF content, fatty acid profile and mRNA levels of genes involved in fatty acid synthesis were determined. The energy levels of the diets significantly (P<0.05 affected the content of IMF, total SFA, total MUFA and total PUFA. C16:0, C18:0 and C18:1n9c account for a large proportion of total fatty acids. Relative expression of acetyl-CoA carboxylase (ACACA, fatty acid synthase (FASN, stearoyl-CoA desaturase (SCD, sterol regulatory element-binding protein-1c (SREBP-1c, peroxisome proliferator-activated receptor γ (PPARγ and fatty acid-binding protein 4 (FABP4 was greater in HE than in LE yaks (P<0.05. Moreover, ME yaks had higher (P<0.05 mRNA expression levels of PPARγ, ACACA, FASN, SCD and FABP4 than did the LE yaks. The results demonstrate that the higher energy level of the diets increased IMF deposition and fatty acid content as well as increased intramuscular lipogenic gene expression during the experimental period.

  2. Specific plasma amino acid disturbances associated with metabolic syndrome

    OpenAIRE

    Siomkajło, Marta; Rybka, Jacek; Mierzchała-Pasierb, Magdalena; Gamian, Andrzej; Stankiewicz-Olczyk, Joanna; Bolanowski, Marek; Daroszewski, Jacek

    2017-01-01

    Purpose The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process. Methods Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(−): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were pe...

  3. Acid-Adaptive Genes of Helicobacter pylori

    Science.gov (United States)

    Wen, Yi; Marcus, Elizabeth A.; Matrubutham, Uday; Gleeson, Martin A.; Scott, David R.; Sachs, George

    2003-01-01

    Helicobacter pylori is the only neutralophile that has been able to colonize the human stomach by using a variety of acid-adaptive mechanisms. One of the adaptive mechanisms is increased buffering due to expression of an acid-activated inner membrane urea channel, UreI, and a neutral pH-optimum intrabacterial urease. To delineate other possible adaptive mechanisms, changes in gene expression in response to acid exposure were examined using genomic microarrays of H. pylori exposed to different levels of external pH (7.4, 6.2, 5.5, and 4.5) for 30 min in the absence and presence of 5 mM urea. Gene expression was correlated with intrabacterial pH measured using 2′,7′-bis-(2-carboxyethyl)-5-carboxyfluorescein and compared to that observed with exposure to 42°C for 30 min. Microarrays containing the 1,534 open reading frames of H. pylori strain 26695 were hybridized with cDNAs from control (pH 7.4; labeled with Cy3) and acidic (labeled with Cy5) conditions. The intrabacterial pH was 8.1 at pH 7.4, fell to 5.3 at pH 4.5, and rose to 6.2 with urea. About 200 genes were up-regulated and ∼100 genes were down-regulated at pH 4.5 in the absence of urea, and about half that number changed in the presence of urea. These genes included pH-homeostatic, transcriptional regulatory, motility, cell envelope, and pathogenicity genes. The up-regulation of some pH-homeostatic genes was confirmed by real-time PCR. There was little overlap with the genes induced by temperature stress. These results suggest that H. pylori has evolved multifaceted acid-adaptive mechanisms enabling it to colonize the stomach that may be novel targets for eliminating infection. PMID:14500513

  4. Identification of metabolism-associated genes and pathways involved in different stages of clear cell renal cell carcinoma.

    Science.gov (United States)

    Li, Hui-Juan; Li, Wen-Xing; Dai, Shao-Xing; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Chen, Bi-Wen; Li, Gong-Hua; Huang, Jing-Fei

    2018-02-01

    The lack of early diagnostic markers and novel therapeutic targets for clear cell renal cell carcinoma (ccRCC) negatively affects patient prognosis. Cancer metabolism is an attractive area for the understanding of the molecular mechanism of carcinogenesis. The present study attempted to identify metabolic changes from the view of the expression of metabolism-associated genes between control samples and those of ccRCC at different disease stages. Data concerning ccRCC gene expression obtained by RNA-sequencing was obtained from The Cancer Genome Atlas and data on metabolism-associated genes were extracted using the Recon2 model. Following analysis of differential gene expression, multiple differentially expressed metabolic genes at each tumor-node-metastasis disease stage were identified, compared with control non-disease samples: Metabolic genes (305) were differentially expressed in stage I disease, 323 in stage II disease, 355 in stage III disease and 363 in stage IV disease. Following enrichment analysis for differential metabolic genes, 22 metabolic pathways were identified to be dysregulated in multiple stages of ccRCC. Abnormalities in hormone, vitamin, glucose and lipid metabolism were present in the early stages of the disease, with dysregulation to reactive oxygen species detoxification and amino acid metabolism pathways occurring with advanced disease stages, particularly to valine, leucine, and isoleucine metabolism, which was substantially dysregulated in stage IV disease. The xenobiotic metabolism pathway, associated with multiple cytochrome P450 family genes, was dysregulated in each stage of the disease. This pathway is worthy of substantial attention since it may aid understanding of drug resistance in ccRCC. The results of the present study offer information to aid further research into early diagnostic biomarkers and therapeutic targets of ccRCC.

  5. A Review of the Metabolic Origins of Milk Fatty Acids

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    Anamaria COZMA

    2013-08-01

    Full Text Available Milk fat and its fatty acid profile are important determinants of the technological, sensorial, and nutritional properties of milk and dairy products. The two major processes contributing to the presence of fatty acids in ruminant milk are the mammary lipogenesis and the lipid metabolism in the rumen. Among fatty acids, 4:0 to 12:0, almost all 14:0 and about a half of 16:0 in milk fat derive from de novo synthesis within the mammary gland. De novo synthesis utilizes as precursors acetate and butyrate produced through carbohydrates ruminal fermentation and involves acetyl-CoA carboxylase and fatty acid synthetase as key enzymes. The rest of 16:0 and all of the long-chain fatty acids derive from mammary uptake of circulating lipoproteins and nonesterified fatty acids that originate from digestive absorption of lipids and body fat mobilization. Further, long-chain fatty acids as well as medium-chain fatty acids entering the mammary gland can be desaturated via Δ-9 desaturase, an enzyme that acts by adding a cis-9-double bond on the fatty acid chain. Moreover, ruminal biohydrogenation of dietary unsaturated fatty acids results in the formation of numerous fatty acids available for incorporation into milk fat. Ruminal biohydrogenation is performed by rumen microbial population as a means of protection against the toxic effects of polyunsaturated fatty acids. Within the rumen microorganisms, bacteria are principally responsible for ruminal biohydrogenation when compared to protozoa and anaerobic fungi.

  6. Oxalic acid production by citric acid-producing Aspergillus niger overexpressing the oxaloacetate hydrolase gene oahA.

    Science.gov (United States)

    Kobayashi, Keiichi; Hattori, Takasumi; Honda, Yuki; Kirimura, Kohtaro

    2014-05-01

    The filamentous fungus Aspergillus niger is used worldwide in the industrial production of citric acid. However, under specific cultivation conditions, citric acid-producing strains of A. niger accumulate oxalic acid as a by-product. Oxalic acid is used as a chelator, detergent, or tanning agent. Here, we sought to develop oxalic acid hyperproducers using A. niger as a host. To generate oxalic acid hyperproducers by metabolic engineering, transformants overexpressing the oahA gene, encoding oxaloacetate hydrolase (OAH; EC 3.7.1.1), were constructed in citric acid-producing A. niger WU-2223L as a host. The oxalic acid production capacity of this strain was examined by cultivation of EOAH-1 under conditions appropriate for oxalic acid production with 30 g/l glucose as a carbon source. Under all the cultivation conditions tested, the amount of oxalic acid produced by EOAH-1, a representative oahA-overexpressing transformant, exceeded that produced by A. niger WU-2223L. A. niger WU-2223L and EOAH-1 produced 15.6 and 28.9 g/l oxalic acid, respectively, during the 12-day cultivation period. The yield of oxalic acid for EOAH-1 was 64.2 % of the maximum theoretical yield. Our method for oxalic acid production gave the highest yield of any study reported to date. Therefore, we succeeded in generating oxalic acid hyperproducers by overexpressing a single gene, i.e., oahA, in citric acid-producing A. niger as a host.

  7. Uric Acid as a Cause of the Metabolic Syndrome.

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    King, Christopher; Lanaspa, Miguel A; Jensen, Thomas; Tolan, Dean R; Sánchez-Lozada, L Gabriela; Johnson, Richard J

    2018-01-01

    Hyperuricemia is common in subjects with obesity, metabolic syndrome, and type 2 diabetes. For many years, hyperuricemia was attributed to the effects of insulin resistance to reduce urinary excretion of uric acid, and it was believed that uric acid may not have any causal role in the metabolic syndrome. However, in recent years, hyperuricemia has been found to independently predict the development of diabetes. Experimental studies have also shown that hyperuricemia may mediate insulin resistance, fatty liver, and dyslipidemia in both fructose-dependent and fructose-independent models of metabolic syndrome. The mechanism for uric acid-induced insulin resistance appears to be mediated by the development of mitochondrial oxidative stress and impairment of insulin-dependent stimulation of nitric oxide in endothelial cells. Pilot studies in humans have reported a potential benefit of lowering serum uric acid on insulin resistance. Large clinical trials are recommended. If uric acid is shown to be a mediator of incident type 2 diabetes in humans, then lowering serum uric acid would represent a simple and inexpensive way to help prevent the development of diabetes and to slow the epidemic. © 2018 S. Karger AG, Basel.

  8. Comparative Transcriptome Analysis Reveals the Influence of Abscisic Acid on the Metabolism of Pigments, Ascorbic Acid and Folic Acid during Strawberry Fruit Ripening.

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    Dongdong Li

    Full Text Available A comprehensive investigation of abscisic acid (ABA biosynthesis and its influence on other important phytochemicals is critical for understanding the versatile roles that ABA plays during strawberry fruit ripening. Using RNA-seq technology, we sampled strawberry fruit in response to ABA or nordihydroguaiaretic acid (NDGA; an ABA biosynthesis blocker treatment during ripening and assessed the expression changes of genes involved in the metabolism of pigments, ascorbic acid (AsA and folic acid in the receptacles. The transcriptome analysis identified a lot of genes differentially expressed in response to ABA or NDGA treatment. In particular, genes in the anthocyanin biosynthesis pathway were actively regulated by ABA, with the exception of the gene encoding cinnamate 4-hydroxylase. Chlorophyll degradation was accelerated by ABA mainly owing to the higher expression of gene encoding pheide a oxygenase. The decrease of β-carotene content was accelerated by ABA treatment and delayed by NDGA. A high negative correlation rate was found between ABA and β-carotene content, indicating the importance of the requirement for ABA synthesis during fruit ripening. In addition, evaluation on the folate biosynthetic pathway indicate that ABA might have minor function in this nutrient's biosynthesis process, however, it might be involved in its homeostasis. Surprisingly, though AsA content accumulated during fruit ripening, expressions of genes involved in its biosynthesis in the receptacles were significantly lower in ABA-treated fruits. This transcriptome analysis expands our understanding of ABA's role in phytochemical metabolism during strawberry fruit ripening and the regulatory mechanisms of ABA on these pathways were discussed. Our study provides a wealth of genetic information in the metabolism pathways and may be helpful for molecular manipulation in the future.

  9. Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis.

    Science.gov (United States)

    Oh, Euhlim; Lu, Mingshou; Park, Changhun; Park, Changhun; Oh, Han Bin; Lee, Sang Yup; Lee, Jinwon

    2011-02-01

    A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/ MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

  10. Analysis of the porcine APOA2 gene expression in liver, polymorphism identification and association with fatty acid composition traits

    NARCIS (Netherlands)

    Ballester, M.; Revilla, M.; Puig-Oliveras, A.; Marchesi, J.A.; Castello, A.; Corominas, J.; Fernandez, A.I.; Folch, J.M.

    2016-01-01

    APOA2 is a protein implicated in triglyceride, fatty acid and glucose metabolism. In pigs, the APOA2 gene is located on pig chromosome 4 (SSC4) in a QTL region affecting fatty acid composition, fatness and growth traits. In this study, we evaluated APOA2 as a candidate gene for meat quality traits

  11. Eicosapentaenoic acid improves metabolic switching in human myotubes

    NARCIS (Netherlands)

    Hessvik, Nina P.; Bakke, Siril S.; Fredriksson, Katarina; Boekschoten, Mark; Fjorkenstad, Anne; Koster, Gerbrand; Hesselink, Matthijs K.; Kersten, Sander; Kase, Eili T.; Rustan, Arild C.; Thoresen, Hege

    2010-01-01

    Metabolically healthy skeletal muscle is characterized by the ability to switch easily between glucose and fat oxidation, whereas loss of this ability seems to be related to insulin resistance. The aim of this study was to investigate whether different fatty acids (FAs) and the LXR ligand T0901317

  12. Transcriptome and Proteome Expression Analysis of the Metabolism of Amino Acids by the Fungus Aspergillus oryzae in Fermented Soy Sauce

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    Guozhong Zhao

    2015-01-01

    Full Text Available Amino acids comprise the majority of the flavor compounds in soy sauce. A portion of these amino acids are formed from the biosynthesis and metabolism of the fungus Aspergillus oryzae; however, the metabolic pathways leading to the formation of these amino acids in A. oryzae remain largely unknown. We sequenced the transcriptomes of A. oryzae 100-8 and A. oryzae 3.042 under similar soy sauce fermentation conditions. 2D gel electrophoresis was also used to find some differences in protein expression. We found that many amino acid hydrolases (endopeptidases, aminopeptidases, and X-pro-dipeptidyl aminopeptidase were expressed at much higher levels (mostly greater than double in A. oryzae 100-8 than in A. oryzae 3.042. Our results indicated that glutamate dehydrogenase may activate the metabolism of amino acids. We also found that the expression levels of some genes changed simultaneously in the metabolic pathways of tyrosine and leucine and that these conserved genes may modulate the function of the metabolic pathway. Such variation in the metabolic pathways of amino acids is important as it can significantly alter the flavor of fermented soy sauce.

  13. Transcriptome and Proteome Expression Analysis of the Metabolism of Amino Acids by the Fungus Aspergillus oryzae in Fermented Soy Sauce.

    Science.gov (United States)

    Zhao, Guozhong; Yao, Yunping; Wang, Chunling; Tian, Fengwei; Liu, Xiaoming; Hou, Lihua; Yang, Zhen; Zhao, Jianxin; Zhang, Hao; Cao, Xiaohong

    2015-01-01

    Amino acids comprise the majority of the flavor compounds in soy sauce. A portion of these amino acids are formed from the biosynthesis and metabolism of the fungus Aspergillus oryzae; however, the metabolic pathways leading to the formation of these amino acids in A. oryzae remain largely unknown. We sequenced the transcriptomes of A. oryzae 100-8 and A. oryzae 3.042 under similar soy sauce fermentation conditions. 2D gel electrophoresis was also used to find some differences in protein expression. We found that many amino acid hydrolases (endopeptidases, aminopeptidases, and X-pro-dipeptidyl aminopeptidase) were expressed at much higher levels (mostly greater than double) in A. oryzae 100-8 than in A. oryzae 3.042. Our results indicated that glutamate dehydrogenase may activate the metabolism of amino acids. We also found that the expression levels of some genes changed simultaneously in the metabolic pathways of tyrosine and leucine and that these conserved genes may modulate the function of the metabolic pathway. Such variation in the metabolic pathways of amino acids is important as it can significantly alter the flavor of fermented soy sauce.

  14. Transcriptome and Proteome Expression Analysis of the Metabolism of Amino Acids by the Fungus Aspergillus oryzae in Fermented Soy Sauce

    Science.gov (United States)

    Zhao, Guozhong; Yao, Yunping; Wang, Chunling; Tian, Fengwei; Liu, Xiaoming; Hou, Lihua; Yang, Zhen; Zhao, Jianxin; Zhang, Hao

    2015-01-01

    Amino acids comprise the majority of the flavor compounds in soy sauce. A portion of these amino acids are formed from the biosynthesis and metabolism of the fungus Aspergillus oryzae; however, the metabolic pathways leading to the formation of these amino acids in A. oryzae remain largely unknown. We sequenced the transcriptomes of A. oryzae 100-8 and A. oryzae 3.042 under similar soy sauce fermentation conditions. 2D gel electrophoresis was also used to find some differences in protein expression. We found that many amino acid hydrolases (endopeptidases, aminopeptidases, and X-pro-dipeptidyl aminopeptidase) were expressed at much higher levels (mostly greater than double) in A. oryzae 100-8 than in A. oryzae 3.042. Our results indicated that glutamate dehydrogenase may activate the metabolism of amino acids. We also found that the expression levels of some genes changed simultaneously in the metabolic pathways of tyrosine and leucine and that these conserved genes may modulate the function of the metabolic pathway. Such variation in the metabolic pathways of amino acids is important as it can significantly alter the flavor of fermented soy sauce. PMID:25945335

  15. Metabolic and endocrine effects of valproic acid chronic treatment.

    Science.gov (United States)

    Belcastro, Vincenzo; D'Egidio, Claudia; Striano, Pasquale; Verrotti, Alberto

    2013-11-01

    Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Endoplasmic Reticulum Stress Regulates Hepatic Bile Acid Metabolism in MiceSummary

    Directory of Open Access Journals (Sweden)

    Anne S. Henkel

    2017-03-01

    Full Text Available Background & Aims: Cholestasis promotes endoplasmic reticulum (ER stress in the liver, however, the effect of ER stress on hepatic bile acid metabolism is unknown. We aim to determine the effect of ER stress on hepatic bile acid synthesis and transport in mice. Methods: ER stress was induced pharmacologically in C57BL/6J mice and human hepatoma (HepG2 cells. The hepatic expression of genes controlling bile acid synthesis and transport was determined. To measure the activity of the primary bile acid synthetic pathway, the concentration of 7α-hydroxy-4-cholesten-3-1 was measured in plasma. Results: Induction of ER stress in mice and HepG2 cells rapidly suppressed the hepatic expression of the primary bile acid synthetic enzyme, cholesterol 7α-hydroxylase. Plasma levels of 7α-hydroxy-4-cholesten-3-1 were reduced in mice subjected to ER stress, indicating impaired bile acid synthesis. Induction of ER stress in mice and HepG2 cells increased expression of the bile salt export pump (adenosine triphosphate binding cassette [Abc]b11 and a bile salt efflux pump (Abcc3. The observed regulation of Cyp7a1, Abcb11, and Abcc3 occurred in the absence of hepatic inflammatory cytokine activation and was not dependent on activation of hepatic small heterodimer partner or intestinal fibroblast growth factor 15. Consistent with suppressed bile acid synthesis and enhanced bile acid export from hepatocytes, prolonged ER stress decreased the hepatic bile acid content in mice. Conclusions: Induction of ER stress in mice suppresses bile acid synthesis and enhances bile acid removal from hepatocytes independently of established bile acid regulatory pathways. These data show a novel function of the ER stress response in regulating bile acid metabolism. Keywords: Unfolded Protein Response, Cyp7a1, 7α-Hydroxy-4-Cholesten-3-1, Bile Acid Synthesis

  17. Impact of dietary precursor ALA versus preformed DHA on fatty acid profiles of eggs, liver and adipose tissue and expression of genes associated with hepatic lipid metabolism in laying hens.

    Science.gov (United States)

    Neijat, M; Eck, P; House, J D

    2017-04-01

    Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), including alpha-linolenic acid (ALA) and preformed longer chain PUFA (LCPUFA, particularly docosahexaenoic acid, DHA) differ in their egg LCPUFA enrichment efficiency. However, mechanisms leading to these differences are unclear. To this end, omega-3 PUFA contents in different lipid classes, including triacylglycerol (TAG) and total phospholipid (PL) in yolk, liver and adipose, as well as the expression of key hepatic enzymes in lipid metabolism were evaluated in laying hens in response to changes in dietary supply. Seventy Lohmann hens (n=10/treatment) consumed either a control diet (0.03% total omega-3 PUFA), or the control with supplementation (0.20%, 0.40% and 0.60% total omega-3 PUFA) from either flaxseed oil or algal product, as sources of ALA (precursor) or DHA (preformed), respectively. The study was arranged in a completely randomized design, and data were analyzed using the Proc Mixed procedure of SAS. ALA accumulated as a function of intake (P<0.0001) in total and lipid classes of yolk, liver and adipose (TAG only) for ALA- and DHA-fed hens. Unlike flaxseed oil, preformed-DHA contributed to greater (P<0.0001) accumulation of LCPUFA in yolk total PL and TAG pool, as well as adipose TAG. This may relate to elevated (P<0.0001) expression of acyl-CoA synthetase (ACSL1). No difference in hepatic EPA level in total lipids was noted between both treatment groups; EPAliver=2.1493x-0.0064; R(2)=0.70, P<0.0001 (x=dietary omega-3 PUFA). The latter result may highlight the role of hepatic EPA in the regulation of LCPUFA metabolism in laying hens. Copyright © 2017. Published by Elsevier Ltd.

  18. Designing medical foods for inherited metabolic disorders: why intact protein is superior to amino acids.

    Science.gov (United States)

    Ney, Denise Marie; Etzel, Mark Raymond

    2017-04-01

    Phenylketonuria and tyrosinemia are inherited metabolic disorders characterized by high blood levels of phenylalanine (Phe) or tyrosine (Tyr), due to mutations in genes affecting Phe and Tyr metabolism, respectively. The primary management is a lifelong diet restricted in protein from natural foods in combination with medical foods comprised mixtures of synthetic amino acids. Compliance is often poor after childhood leading to neuropsychological sequela. Glycomacropeptide, an intact 64 amino acid glycophosphopeptide isolated from cheese whey, provides a new paradigm for the management of phenylketonuria and tyrosinemia because glycomacropeptide contains no Phe and Tyr in its pure form, and is also a prebiotic. Medical foods made from glycomacropeptide have been used successfully for the management of phenylketonuria and tyrosinemia. Preclinical and clinical studies demonstrate that intact protein from glycomacropeptide provides a more acceptable and physiologic source of defined protein compared to amino acids in medical foods. For example, harmful gut bacteria were reduced, beneficial short chain fatty acids increased, renal workload decreased, protein utilization increased, and bone fragility decreased using intact protein versus amino acids. Advances in biotechnology will propel the transition from synthetic amino acids to intact proteins for the management of inherited metabolic disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Vitamin D Metabolism Genes in Asthma and Atopy.

    Science.gov (United States)

    Morales, Eva; Sanchez-Solis, Manuel; Garcia-Marcos, Luis

    2015-01-01

    Asthma and allergy are complex diseases influenced by poorly understood environmental and genetic factors. The innate and adaptive immune systems play an important role in the pathogenesis of these diseases. Many genes involved in inflammation and immunoregulation pathways have been related to asthma and allergy susceptibility. Among the diverse extra-skeletal actions of vitamin D, growing evidence indicates that vitamin D is an important modulator of the immune system response and may influence the development of asthma and allergy susceptibility through different mechanisms. The vitamin D pathway is under the control of a set of polymorphic genes that code for key enzymes which regulate the synthesis and metabolism of vitamin D (i.e. CYP27A1, GC, CYP27B1 and CYP24A1) and of genes that encode for downstream mediators of vitamin D signalling (i.e. VDR, RXR, PPAR, NCOA and SMAD). This metabolism gene pathway is of fundamental importance in regulating vitamin D availability and biological response. Unravelling the role of vitamin D metabolism genes on asthma and atopy susceptibility may help to understand the impact of vitamin D on the development of these disorders. This review article aims: 1) to describe the genetics of the vitamin D pathway, 2) to revise the potential mechanisms by which vitamin D pathway genes may affect the immune and respiratory systems predisposing to asthma and allergy disorders; and 3) to summarize the influence of genetic variation on vitamin D pathway genes on the development of asthma and allergy.

  20. Pleiotropic genes for metabolic syndrome and inflammation

    DEFF Research Database (Denmark)

    Kraja, Aldi T; Chasman, Daniel I; North, Kari E

    2014-01-01

    , PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional...

  1. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-09-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production.

  2. Metabolic evolution of Escherichia coli strains that produce organic acids

    Science.gov (United States)

    Grabar, Tammy; Gong, Wei; Yocum, R Rogers

    2014-10-28

    This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.

  3. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    Directory of Open Access Journals (Sweden)

    Hitomi Maruta

    Full Text Available Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4 genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A, which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  4. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    Science.gov (United States)

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  5. 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.

  6. Efeito dos ácidos graxos n-3 e n-6 na expressão de genes do metabolismo de lipídeos e risco de aterosclerose Effects of n-3 and n-6 fatty acids on the expression of genes involved in the lipid metabolism and risk of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Helena Fonseca Raposo

    2010-10-01

    mortality in Western populations. Roughly 17.5 million people died from cardiovascular diseases in 2005, representing 30% of the causes of death in that year, and in 2015, another 20 million people will die of cardiovascular diseases around the world. The n-3 fatty acids, especially the long-chain n-3 found in fish, have been shown to be particularly effective in the prevention and treatment of diseases such as dyslipidemias, diabetes mellitus and obesity, presenting an important cardioprotective effect. In this context, studies have found that at least some of the cardiovascular benefits associated with eicosapentaenoic and docosahexaenoic fatty acids regard the modulation of genes that respond to the peroxisome proliferator-activated receptors involved in lipid metabolism. This review will discuss some of the mechanisms of action of some n-3 and n-6 fatty acids on the metabolism of lipids and lipoproteins. In conclusion, many aspects that contribute to the risk of cardiovascular diseases are affected by n-3 intake. N-3 fatty acids not only reduce triglycerides, but also promote factors that increase adiponectin, reduce blood cholesterol levels and improve the reverse cholesterol transport, and all of these contribute to reducing the risk of atherosclerosis. However, additional studies are still necessary to elucidate all the cellular and molecular mechanisms responsible for the cardioprotective effect of n-3 fatty acids.

  7. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    Science.gov (United States)

    Wotring, Virginia E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2010-01-01

    Most pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  8. Tanycytes and a differential fatty acid metabolism in the hypothalamus.

    Science.gov (United States)

    Hofmann, Kristina; Lamberz, Christian; Piotrowitz, Kira; Offermann, Nina; But, Diana; Scheller, Anja; Al-Amoudi, Ashraf; Kuerschner, Lars

    2017-02-01

    Although the brain controls all main metabolic pathways in the whole organism, its lipid metabolism is partially separated from the rest of the body. Circulating lipids and other metabolites are taken up into brain areas like the hypothalamus and are locally metabolized and sensed involving several hypothalamic cell types. In this study we show that saturated and unsaturated fatty acids are differentially processed in the murine hypothalamus. The observed differences involve both lipid distribution and metabolism. Key findings were: (i) hypothalamic astrocytes are targeted by unsaturated, but not saturated lipids in lean mice; (ii) in obese mice labeling of these astrocytes by unsaturated oleic acid cannot be detected unless β-oxidation or ketogenesis is inhibited; (iii) the hypothalamus of obese animals increases ketone body and neutral lipid synthesis while tanycytes, hypothalamic cells facing the ventricle, increase their lipid droplet content; and (iv) tanycytes show different labeling for saturated or unsaturated lipids. Our data support a metabolic connection between tanycytes and astrocytes likely to impact hypothalamic lipid sensing. GLIA 2017;65:231-249. © 2016 Wiley Periodicals, Inc.

  9. Drug metabolizing enzyme and transporter gene variation, nicotine metabolism, prospective abstinence, and cigarette consumption

    OpenAIRE

    Bergen, Andrew W; Martha Michel; Denise Nishita; Ruth Krasnow; Javitz, Harold S.; Conneely, Karen N; Lessov-Schlaggar, Christina N.; Hyman Hops; Zhu, Andy Z. X.; Baurley, James W; McClure, Jennifer B.; Hall, Sharon M.; Baker, Timothy B; Conti, David V; Benowitz, Neal L.

    2015-01-01

    © 2015 Bergen et al. The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a met...

  10. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    James P. Hardwick

    2009-01-01

    Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

  11. Heart and bile acids - Clinical consequences of altered bile acid metabolism.

    Science.gov (United States)

    Vasavan, Tharni; Ferraro, Elisa; Ibrahim, Effendi; Dixon, Peter; Gorelik, Julia; Williamson, Catherine

    2018-01-06

    Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1.

    Science.gov (United States)

    Kim, Minji; Furuzono, Tomoya; Yamakuni, Kanae; Li, Yongjia; Kim, Young-Il; Takahashi, Haruya; Ohue-Kitano, Ryuji; Jheng, Huei-Fen; Takahashi, Nobuyuki; Kano, Yuriko; Yu, Rina; Kishino, Shigenobu; Ogawa, Jun; Uchida, Kunitoshi; Yamazaki, Jun; Tominaga, Makoto; Kawada, Teruo; Goto, Tsuyoshi

    2017-11-01

    Gut microbiota can regulate the host energy metabolism; however, the underlying mechanisms that could involve gut microbiota-derived compounds remain to be understood. Therefore, in this study, we investigated the effects of KetoA [10-oxo-12(Z)-octadecenoic acid]-a linoleic acid metabolite produced by gut lactic acid bacteria-on whole-body energy metabolism and found that dietary intake of KetoA could enhance energy expenditure in mice, thereby protecting mice from diet-induced obesity. By using Ca2+ imaging and whole-cell patch-clamp methods, KetoA was noted to potently activate transient receptor potential vanilloid 1 (TRPV1) and enhance noradrenalin turnover in adipose tissues. In addition, KetoA up-regulated genes that are related to brown adipocyte functions, including uncoupling protein 1 (UCP1) in white adipose tissue (WAT), which was later diminished in the presence of a β-adrenoreceptor blocker. By using obese and diabetic model KK-Ay mice, we further show that KetoA intake ameliorated obesity-associated metabolic disorders. In the absence of any observed KetoA-induced antiobesity effect or UCP1 up-regulation in TRPV1-deficient mice, we prove that the antiobesity effect of KetoA was caused by TRPV1 activation-mediated browning in WAT. KetoA produced in the gut could therefore be involved in the regulation of host energy metabolism.-Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.-I., Takahashi, H., Ohue-Kitano, R., Jheng, H.-F., Takahashi, N., Kano, Y., Yu, R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T., Goto, T. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1. © FASEB.

  13. Adaptations to climate in candidate genes for common metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Angela M Hancock

    2008-02-01

    Full Text Available Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.

  14. Gene expression phenotypes for lipid metabolism and intramuscular fat in skeletal muscle of cattle.

    Science.gov (United States)

    De Jager, N; Hudson, N J; Reverter, A; Barnard, R; Cafe, L M; Greenwood, P L; Dalrymple, B P

    2013-03-01

    Gene expression phenotypes were evaluated for intramuscular fat (IMF) in bovine skeletal muscle as an alternative to traditional estimates of IMF%. Gene expression data from a time course of LM development in high- and low-marbling Bos taurus cattle crosses were compared to identify genes involved in intramuscular adipocyte lipid metabolism with developmentally similar gene expression profiles. Three sets of genes were identified: triacylglyceride (TAG) synthesis and storage, fatty acid (FA) synthesis, and PPARγ-related genes. In an independent analysis in the LM of 48 Bos indicus cattle, TAG and FA gene sets were enriched in the top 100 genes of which expression was most correlated with IMF% (P = 1.2 × 10(-24) and 3.5 × 10(-9), respectively). In general, genes encoding enzymes involved in the synthesis of FA and TAG in the intramuscular adipocytes were present in the top 100 genes. In B. indicus, effects of a steroid hormone growth promotant (HGP), 2 experimental sites [New South Wales (NSW) and Western Australia (WA)], and 3 tenderness genotypes on the expression levels of genes in the TAG gene set and the correlation of gene expression with IMF% were investigated. Although correlation between expression of 12 individual TAG genes and IMF% was observed in HGP-treated animals in both experimental sites (mean r = 0.43), correlation was not observed for untreated animals at the NSW site (mean r = -0.07, P 0.05) on the correlation of TAG genes with IMF%. In general, the interactions among genotype, treatment and location, and TAG gene set gene expression were consistent with the interactions among the same factors and IMF% detected using 255 animals, of which the 48 in this study were a subset. Thus, the TAG gene set constitutes a gene expression phenotype able to predict effects of different genotypes and treatments on IMF% using much smaller groups than current approaches, even in animals with very low IMF%.

  15. Horizontal transfer of carbohydrate metabolism genes into ectomycorrhizal Amanita.

    Science.gov (United States)

    Chaib De Mares, Maryam; Hess, Jaqueline; Floudas, Dimitrios; Lipzen, Anna; Choi, Cindy; Kennedy, Megan; Grigoriev, Igor V; Pringle, Anne

    2015-03-01

    The genus Amanita encompasses both symbiotic, ectomycorrhizal fungi and asymbiotic litter decomposers; all species are derived from asymbiotic ancestors. Symbiotic species are no longer able to degrade plant cell walls. The carbohydrate esterases family 1 (CE1s) is a diverse group of enzymes involved in carbon metabolism, including decomposition and carbon storage. CE1 genes of the ectomycorrhizal A. muscaria appear diverged from all other fungal homologues, and more similar to CE1s of bacteria, suggesting a horizontal gene transfer (HGT) event. In order to test whether AmanitaCE1s were acquired horizontally, we built a phylogeny of CE1s collected from across the tree of life, and describe the evolution of CE1 genes among Amanita and relevant lineages of bacteria. CE1s of symbiotic Amanita were very different from CE1s of asymbiotic Amanita, and are more similar to bacterial CE1s. The protein structure of one CE1 gene of A. muscaria matched a depolymerase that degrades the carbon storage molecule poly((R)-3-hydroxybutyrate) (PHB). Asymbiotic Amanita do not carry sequence or structural homologues of these genes. The CE1s acquired through HGT may enable novel metabolisms, or play roles in signaling or defense. This is the first evidence for the horizontal transfer of carbohydrate metabolism genes into ectomycorrhizal fungi. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  16. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

    Directory of Open Access Journals (Sweden)

    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  17. Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxy fatty acid of industrial importance.

    Science.gov (United States)

    Meesapyodsuk, Dauenpen; Chen, Yan; Ng, Siew Hon; Chen, Jianan; Qiu, Xiao

    2015-11-01

    Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fatty acid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a "push" (synthesis) and "pull" (assembly) strategy. CpFAH, a fatty acid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fatty acid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid produced was mainly distributed in the neutral lipid fractions, particularly the free fatty acid form, but with little in the polar lipids. This work demonstrates the effectiveness of the metabolic engineering strategy and excellent capacity of the microbial system for production of ricinoleic acid as an alternative to plant sources for industrial uses. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  18. Genetic variations in androgen metabolism genes and associations ...

    African Journals Online (AJOL)

    We investigated the role of genetic variants in the androgen metabolism genes and the probability of developing PCa in South African coloured and white men. Methods. Genotype and allele counts and frequencies of single nucleotide polymorphisms (SNPs) in CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured ...

  19. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2016-05-01

    Full Text Available Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient–host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control and hippocampus (cognitive processing from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  20. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Science.gov (United States)

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Comparative metabolic pathway analysis with special reference to nucleotide metabolism-related genes in chicken primordial germ cells.

    Science.gov (United States)

    Rengaraj, Deivendran; Lee, Bo Ram; Jang, Hyun-Jun; Kim, Young Min; Han, Jae Yong

    2013-01-01

    Metabolism provides energy and nutrients required for the cellular growth, maintenance, and reproduction. When compared with genomics and proteomics, metabolism studies provide novel findings in terms of cellular functions. In this study, we examined significant and differentially expressed genes in primordial germ cells (PGCs), gonadal stromal cells, and chicken embryonic fibroblasts compared with blastoderms using microarray. All upregulated genes (1001, 1118, and 974, respectively) and downregulated genes (504, 627, and 1317, respectively) in three test samples were categorized into functional groups according to gene ontology. Then all selected genes were tested to examine their involvement in metabolic pathways through Kyoto Encyclopedia of Genes and Genomes pathway database using overrepresentation analysis. In our results, most of the upregulated and downregulated genes were involved in at least one subcategory of seven major metabolic pathways. The main objective of this study is to compare the PGC expressed genes and their metabolic pathways with blastoderms, gonadal stromal cells, and chicken embryonic fibroblasts. Among the genes involved in metabolic pathways, a higher number of PGC upregulated genes were identified in retinol metabolism, and a higher number of PGC downregulated genes were identified in sphingolipid metabolism. In terms of the fold change, acyl-CoA synthetase medium-chain family member 3 (ACSM3), which is involved in butanoate metabolism, and N-acetyltransferase, pineal gland isozyme NAT-10 (PNAT10), which is involved in energy metabolism, showed higher expression in PGCs. To validate these gene changes, the expression of 12 nucleotide metabolism-related genes in chicken PGCs was examined by real-time polymerase chain reaction. The results of this study provide new information on the expression of genes associated with metabolism function of PGCs and will facilitate more basic research on animal PGC differentiation and function

  2. Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

    Science.gov (United States)

    Engberink, Mariëlle F.; Brink, Elizabeth J.; van Baak, Marleen A.; Joosten, Michel M.; Gans, Reinold O.B.; Navis, Gerjan; Bakker, Stephan J.L.

    2012-01-01

    Summary Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. This study examined the association of metabolic acid load with acidosis and with cardiovascular risk factors in RTRs and aimed to identify dietary factors associated with acidosis. Design, participants, setting, & measurements 707 RTRs were included. Metabolic acid load was assessed by measuring 24-hour urinary net acid excretion (NAE; i.e., titratable acid + ammonium − bicarbonate). Acidosis was defined as serum [HCO3−] acidosis and between dietary factors and acidosis. Results Mean age ± SD was 53±13 years; 57% of patients were male. Acidosis was present in 31% of RTRs. NAE was associated with acidosis (serum HCO3−: β=−0.61; serum pH: β=−0.010; both Pacidosis, diet might influence acid-base homeostasis in RTRs. Higher intake of fruits and vegetables and lower animal protein intake is associated with less acidosis in RTRs. PMID:22935845

  3. Lactococcus lactis metabolism and gene expression during growth on plant tissues.

    Science.gov (United States)

    Golomb, Benjamin L; Marco, Maria L

    2015-01-01

    Lactic acid bacteria have been isolated from living, harvested, and fermented plant materials; however, the adaptations these bacteria possess for growth on plant tissues are largely unknown. In this study, we investigated plant habitat-specific traits of Lactococcus lactis during growth in an Arabidopsis thaliana leaf tissue lysate (ATL). L. lactis KF147, a strain originally isolated from plants, exhibited a higher growth rate and reached 7.9-fold-greater cell densities during growth in ATL than the dairy-associated strain L. lactis IL1403. Transcriptome profiling (RNA-seq) of KF147 identified 853 induced and 264 repressed genes during growth in ATL compared to that in GM17 laboratory culture medium. Genes induced in ATL included those involved in the arginine deiminase pathway and a total of 140 carbohydrate transport and metabolism genes, many of which are involved in xylose, arabinose, cellobiose, and hemicellulose metabolism. The induction of those genes corresponded with L. lactis KF147 nutrient consumption and production of metabolic end products in ATL as measured by gas chromatography-time of flight mass spectrometry (GC-TOF/MS) untargeted metabolomic profiling. To assess the importance of specific plant-inducible genes for L. lactis growth in ATL, xylose metabolism was targeted for gene knockout mutagenesis. Wild-type L. lactis strain KF147 but not an xylA deletion mutant was able to grow using xylose as the sole carbon source. However, both strains grew to similarly high levels in ATL, indicating redundancy in L. lactis carbohydrate metabolism on plant tissues. These findings show that certain strains of L. lactis are well adapted for growth on plants and possess specific traits relevant for plant-based food, fuel, and feed fermentations. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Fatty Acids in Energy Metabolism of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Alexander Panov

    2014-01-01

    Full Text Available In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain’s energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

  5. Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism

    Directory of Open Access Journals (Sweden)

    Eric Kwong

    2015-03-01

    Full Text Available The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease (NAFLD, obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids (CBA activate the extracellular regulated protein kinases (ERK1/2 and protein kinase B (AKT signaling pathway via sphingosine-1-phosphate receptor 2 (S1PR2. CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2 (SphK2 and hepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism.

  6. Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism.

    Science.gov (United States)

    Kwong, Eric; Li, Yunzhou; Hylemon, Phillip B; Zhou, Huiping

    2015-03-01

    The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease (NAFLD), obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids (CBA) activate the extracellular regulated protein kinases (ERK1/2) and protein kinase B (AKT) signaling pathway via sphingosine-1-phosphate receptor 2 (S1PR2). CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2 (SphK2) and hepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism.

  7. Adaptive Evolution of Energy Metabolism-Related Genes in Hypoxia-Tolerant Mammals.

    Science.gov (United States)

    Tian, Ran; Yin, Daiqing; Liu, Yanzhi; Seim, Inge; Xu, Shixia; Yang, Guang

    2017-01-01

    Animals that are able to sustain life under hypoxic conditions have long captured the imagination of biologists and medical practitioners alike. Although the associated morphological modifications have been extensively described, the mechanisms underlying the evolution of hypoxia tolerance are not well understood. To provide such insights, we investigated genes in four major energy metabolism pathways, and provide evidence of distinct evolutionary paths to mammalian hypoxia-tolerance. Positive selection of genes in the oxidative phosphorylation pathway mainly occurred in terrestrial hypoxia-tolerant species; possible adaptations to chronically hypoxic environments. The strongest candidate for positive selection along cetacean lineages was the citrate cycle signaling pathway, suggestive of enhanced aerobic metabolism during and after a dive. Six genes with cetacean-specific amino acid changes are rate-limiting enzymes involved in the gluconeogenesis pathway, which would be expected to enhance the lactate removal after diving. Intriguingly, 38 parallel amino acid substitutions in 29 genes were observed between hypoxia-tolerant mammals. Of these, 76.3% were radical amino acid changes, suggesting that convergent molecular evolution drives the adaptation to hypoxic stress and similar phenotypic changes. This study provides further insights into life under low oxygen conditions and the evolutionary trajectories of hypoxia-tolerant species.

  8. Adaptive Evolution of Energy Metabolism-Related Genes in Hypoxia-Tolerant Mammals

    Directory of Open Access Journals (Sweden)

    Ran Tian

    2017-12-01

    Full Text Available Animals that are able to sustain life under hypoxic conditions have long captured the imagination of biologists and medical practitioners alike. Although the associated morphological modifications have been extensively described, the mechanisms underlying the evolution of hypoxia tolerance are not well understood. To provide such insights, we investigated genes in four major energy metabolism pathways, and provide evidence of distinct evolutionary paths to mammalian hypoxia-tolerance. Positive selection of genes in the oxidative phosphorylation pathway mainly occurred in terrestrial hypoxia-tolerant species; possible adaptations to chronically hypoxic environments. The strongest candidate for positive selection along cetacean lineages was the citrate cycle signaling pathway, suggestive of enhanced aerobic metabolism during and after a dive. Six genes with cetacean-specific amino acid changes are rate-limiting enzymes involved in the gluconeogenesis pathway, which would be expected to enhance the lactate removal after diving. Intriguingly, 38 parallel amino acid substitutions in 29 genes were observed between hypoxia-tolerant mammals. Of these, 76.3% were radical amino acid changes, suggesting that convergent molecular evolution drives the adaptation to hypoxic stress and similar phenotypic changes. This study provides further insights into life under low oxygen conditions and the evolutionary trajectories of hypoxia-tolerant species.

  9. Dietary Gut Microbial Metabolites, Short-chain Fatty Acids, and Host Metabolic Regulation

    Directory of Open Access Journals (Sweden)

    Mayu Kasubuchi

    2015-04-01

    Full Text Available During feeding, the gut microbiota contributes to the host energy acquisition and metabolic regulation thereby influencing the development of metabolic disorders such as obesity and diabetes. Short-chain fatty acids (SCFAs such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC. Recent evidence suggests that dietary fiber and the gut microbial-derived SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal environment, but also by directly affecting various host peripheral tissues. In this review, we summarize the roles of gut microbial SCFAs in the host energy regulation and present an overview of the current understanding of its physiological functions.

  10. Toxicogenomic analysis suggests chemical-induced sexual dimorphism in the expression of metabolic genes in zebrafish liver.

    Directory of Open Access Journals (Sweden)

    Xun Zhang

    Full Text Available Differential gene expression in two sexes is widespread throughout the animal kingdom, giving rise to sex-dimorphic gene activities and sex-dependent adaptability to environmental cues, diets, growth and development as well as susceptibility to diseases. Here, we present a study using a toxicogenomic approach to investigate metabolic genes that show sex-dimorphic expression in the zebrafish liver triggered by several chemicals. Our analysis revealed that, besides the known genes for xenobiotic metabolism, many functionally diverse metabolic genes, such as ELOVL fatty acid elongase, DNA-directed RNA polymerase, and hydroxysteroid dehydrogenase, were also sex-dimorphic in their response to chemical treatments. Moreover, sex-dimorphic responses were also observed at the pathway level. Pathways belonging to xenobiotic metabolism, lipid metabolism, and nucleotide metabolism were enriched with sex-dimorphically expressed genes. We also observed temporal differences of the sex-dimorphic responses, suggesting that both genes and pathways are differently correlated during different periods of chemical perturbation. The ubiquity of sex-dimorphic activities at different biological hierarchies indicate the importance and the need of considering the sex factor in many areas of biological researches, especially in toxicology and pathology.

  11. Effect of supplemental β-carotene compared to retinyl palmitate on fatty acid profile and expression of mRNA from genes involved in vitamin A metabolism in beef feedlot cattle.

    Science.gov (United States)

    Condron, Kaitlin N; Waddell, Jolena N; Claeys, Matt C; Lemenager, Ronald P; Schoonmaker, Jon P

    2017-09-01

    To examine the effects of dietary β-carotene (βC) or retinyl palmitate (RP) on fatty acid (FA) profile and mRNA expression, samples were collected from 24 Angus-cross calves that were allotted to four treatments consisting of RP supplemented at 2200 IU/kg, and synthetic β-carotene (SβC) supplemented at one, five or 10 times RP. Longissimus muscle (LM) cis-9, trans-11 conjugated linoleic acid was greater in RP compared to SβC1X (P = 0.04). The polyunsaturated:saturated FA increased linearly (P = 0.04) in the LM as dietary SβC increased. Expression of βC oxygenase 2 (βCO2), an enzyme that cleaves β-carotene, was greater in the LM for SβC1X compared to RP and decreased linearly as SβC increased (P ≤ 0.02). Peroxisome proliferator activated receptor γ (PPARγ) expression in the LM increased in SβC1X compared to RP (P = 0.03); however, PPARγ and retinoic acid X receptor α (RXRα) expression decreased linearly (P = 0.02) in the LM with increasing SβC. Retinoic acid receptor α (RARα) expression tended (P = 0.10) to decrease linearly in the LM with increased SβC. In conclusion, SβC supplementation increased mRNA expression of some lipogenic genes in the LM, but increasing dietary SβC inhibited their expression and tended to increase polyunsaturated FA. © 2017 Japanese Society of Animal Science.

  12. Inflammation and ER Stress Regulate Branched-Chain Amino Acid Uptake and Metabolism in Adipocytes

    Science.gov (United States)

    Burrill, Joel S.; Long, Eric K.; Reilly, Brian; Deng, Yingfeng; Armitage, Ian M.; Scherer, Philipp E.

    2015-01-01

    Inflammation plays a critical role in the pathology of obesity-linked insulin resistance and is mechanistically linked to the effects of macrophage-derived cytokines on adipocyte energy metabolism, particularly that of the mitochondrial branched-chain amino acid (BCAA) and tricarboxylic acid (TCA) pathways. To address the role of inflammation on energy metabolism in adipocytes, we used high fat-fed C57BL/6J mice and lean controls and measured the down-regulation of genes linked to BCAA and TCA cycle metabolism selectively in visceral but not in subcutaneous adipose tissue, brown fat, liver, or muscle. Using 3T3-L1 cells, TNFα, and other proinflammatory cytokine treatments reduced the expression of the genes linked to BCAA transport and oxidation. Consistent with this, [14C]-leucine uptake and conversion to triglycerides was markedly attenuated in TNFα-treated adipocytes, whereas the conversion to protein was relatively unaffected. Because inflammatory cytokines lead to the induction of endoplasmic reticulum stress, we evaluated the effects of tunicamycin or thapsigargin treatment of 3T3-L1 cells and measured a similar down-regulation in the BCAA/TCA cycle pathway. Moreover, transgenic mice overexpressing X-box binding protein 1 in adipocytes similarly down-regulated genes of BCAA and TCA metabolism in vivo. These results indicate that inflammation and endoplasmic reticulum stress attenuate lipogenesis in visceral adipose depots by down-regulating the BCAA/TCA metabolism pathway and are consistent with a model whereby the accumulation of serum BCAA in the obese insulin-resistant state is linked to adipose inflammation. PMID:25635940

  13. Valproic Acid related metabolic syndrome in patients with epilepsy.

    Science.gov (United States)

    Mania, M; Kasradze, S; Okujava, N

    2011-05-01

    Valproic acid (VPA) is an anticonvulsant and mood-stabilizing drug for the long-term treatment. It is established that VPA has number of side effects affecting metabolic and endocrine system, like weight gain, hyperinsulinemia, changes in sex hormones, dyslipidemia, hyperleptinemia and etc. But the data are not sufficient to judge if VPA treatment can induce metabolic syndrome. Our aim was to investigate metabolic syndrome frequency in VPA-treated (n=11) and CBZ-treated (n=13) patients with epilepsy and in drug-free healthy subjects (n=11). We diagnosed metabolic syndrome according to Adult Treatment Panel III criteria (ATP III). We took blood samples for analysing triglyceride, HDL cholesterol and fasting glucose. Waist circumference and blood pressure was measured as well. Our data revealed that metabolic syndrome is relatively frequent in VPA-treated patients group (45,5%) compared with CBZ group and controls (15.4% and 27.3% respectively) (pmetabolic syndrome in patients with epilepsy, but BMI did not differ between VPA monotherapy study group, CBZ monotherapy study group and controls.

  14. Radiometric measurement of differential metabolism of fatty acid by mycobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, E.E.; Kertcher, J.A.; Larson, S.M.; Tepper, B.S.; Wagner, H.N. Jr.

    1982-06-01

    An assay system has been developed based on automated radiometric quantification of /sup 14/CO2 produced through oxidation of (1-/sup 14/C) fatty acids by mycobacteria. Two stains of M. tuberculosis (H37Rv and Erdman) and one of M. bovis (BCG) in 7H9 medium (ADC) with 1.0 microCi of one of the fatty acids (butyric, hexanoic, octanoic, decanoic, lauric, myristic, palmitic, stearic, oleic, linoleic and linolenic) were studied. Results previously published on M. lepraemurium (Hawaiian) were also included for comparison. Both strains of M. tuberculosis had maximum /sup 14/CO2 production from hexanoic acid. Oxidation of butyric and avid oxidation of lauric acids were also found with the H37Rv strain but not with Erdman. In contrast, /sup 14/CO2 production by M. bovis was greatest from lauric and somewhat less from decanoic acid. M. lepraemurium showed increasing oxidation rates from myristic, decanoic and lauric acids. Assimilation studies of M. tuberculosis H37Rv confirmed that most of the oxidized substrates were converted into by-products with no change in those from which no oxidation was found. These data suggest that the radiometric measurement of differential fatty acid metabolism may provide a basis of strain identification of the genus Mycobacterium.

  15. Icariin Is A PPARα Activator Inducing Lipid Metabolic Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Yuan-Fu Lu

    2014-11-01

    Full Text Available Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2 were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1 and FA synthetase (Fasn were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes.

  16. Impaired long-chain fatty acid utilization by cardiac myocytes isolated from mice lacking the heart-type fatty acid binding protein gene

    NARCIS (Netherlands)

    Schaap, F. G.; Binas, B.; Danneberg, H.; van der Vusse, G. J.; Glatz, J. F.

    1999-01-01

    Heart-type fatty acid binding protein (H-FABP), abundantly expressed in cardiac myocytes, has been postulated to facilitate the cardiac uptake of long-chain fatty acids (LCFAs) and to promote their intracellular trafficking to sites of metabolic conversion. Mice with a disrupted H-FABP gene were

  17. ApoM: gene regulation and effects on HDL metabolism

    DEFF Research Database (Denmark)

    Nielsen, Lars B; Christoffersen, Christina; Ahnström, Josefin

    2009-01-01

    and glucose metabolism. Although the concentration of plasma apoM correlates with that of cholesterol, apoM was not identified as a risk factor for cardiovascular disease in two prospective studies. In genetically modified mice, however, changes in plasma apoM concentration caused quantitative and qualitative...... changes in HDLs, and overexpression of the apoM gene reduced atherosclerosis. In conclusion, it seems that apoM plays a part in lipoprotein metabolism; however, the biological impact of apoM in humans remains to be determined....

  18. Genetic Variation in Bile Acid Metabolism: Implications for Lipoprotein Homeostasis

    NARCIS (Netherlands)

    Hofman, M.K.

    2005-01-01

    Genetic factors play an important role in the homeostasis of cholesterol in the human body. An important pathway for eliminating cholesterol from the body is to convert it into bile acids in the liver. The rate-limiting enzyme in this catabolism of cholesterol is CYP7A1. In the gene of CYP7A1, a

  19. Folate nutrigenetics: a convergence of dietary folate metabolism, folic acid supplementation, and folate antagonist pharmacogenetics.

    Science.gov (United States)

    Meshkin, Brian; Blum, Kenneth

    2007-01-01

    Folate (Vitamin B9, Folic acid, folinic acid, folacin, pteroyglutamic acid) is essential for life-sustaining processes of DNA synthesis, replication, and repair which are naturally present in common foods such as peas, oranges, broccoli, and whole-wheat products. Folate levels have been associated with birth defects, cardiovascular disease, and many other important healthcare issues, which has resulted in government-mandated food fortification to deliver minimum levels of intake. Despite this one-size-fits-all recommendation by governmental regulatory bodies, studies suggest that a genetic predisposition may exist within as much as 67% (combining both the CT and TT alleles) of the population that causes a metabolic folate deficiency. Thus, genetic factors may play an important role in folate levels and metabolism. A substantial body of scientific evidence supports the importance of folate, genes associated with folate, genes associated with anti-folate therapeutics, and thereby a convergence in nutritional genetics or nutrigenetics. This review will comment on the substantial body of scientific evidence demonstrating the relevance for nutrigenetic measurements to guide dietary folate intake and nutritional supplementation with folic acid.

  20. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    Science.gov (United States)

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-04

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

  1. Gene expression and metabolism preceding soft scald, a chilling injury of 'Honeycrisp' apple fruit.

    Science.gov (United States)

    Leisso, Rachel S; Gapper, Nigel E; Mattheis, James P; Sullivan, Nathanael L; Watkins, Christopher B; Giovannoni, James J; Schaffer, Robert J; Johnston, Jason W; Hanrahan, Ines; Hertog, Maarten L A T M; Nicolaï, Bart M; Rudell, David R

    2016-10-12

    'Honeycrisp' is an apple cultivar that is susceptible to soft scald, a chilling injury expressed as necrotic patches on the peel. Improved understanding of metabolism associated with the disorder would improve our understanding of soft scald and contribute to developing more effective management strategies for apple storage. It was expected that specific gene expression and specific metabolite levels in the peel would be linked with soft scald risk at harvest and/or specific time points during cold storage. Fruit from nine 'Honeycrisp' apple orchards that would eventually develop different incidences of soft scald between 4 and 8 weeks of cold air storage were used to contrast and determine differential transcriptomic and metabolomic changes during storage. Untargeted metabolic profiling revealed changes in a number of distinct pathways preceding and concurrent with soft scald symptom development, including elevated γ-aminobutryic acid (GABA), 1-hexanol, acylated steryl glycosides, and free p-coumaryl acyl esters. At harvest, levels of sesquiterpenoid and triterpenoid acyl esters were relatively higher in peel of fruit that did not later develop the disorder. RNA-seq driven gene expression profiling highlighted possible involvement of genes and associated metabolic processes with soft scald development. These included elevated expression of genes involved in lipid peroxidation and phenolic metabolism in fruit with soft scald, and isoprenoid/brassinosteroid metabolism in fruit that did not develop soft scald. Expression of other stress-related genes in fruit that developed soft scald included chlorophyll catabolism, cell wall loosening, and lipid transport while superoxide dismutases were up-regulated in fruit that did not develop the disorder. This study delineates the sequential transcriptomic and metabolomic changes preceding soft scald symptom development. Changes were differential depending on susceptibility of fruit to the disorder and could be attributed to

  2. Current progress towards the metabolic engineering of plant seed oil for hydroxy fatty acids production.

    Science.gov (United States)

    Lee, Kyeong-Ryeol; Chen, Grace Q; Kim, Hyun Uk

    2015-04-01

    Hydroxy fatty acids produced in plant seed oil are important industrial material. This review focuses on the use of metabolic engineering approaches for the production of hydroxy fatty acids in transgenic plants. Vegetable oil is not only edible but can also be used for industrial purposes. The industrial demand for vegetable oil will increase with the continued depletion of fossil fuels and ensuing environmental issues such as climate change, caused by increased carbon dioxide in the air. Some plants accumulate high levels of unusual fatty acids in their seeds, and these fatty acids (FAs) have properties that make them suitable for industrial applications. Hydroxy fatty acids (HFAs) are some of the most important of these industrial FAs. Castor oil is the conventional source of HFA. However, due to the presence of toxin ricin in its seeds, castor is not cultivated on a large scale. Lesquerella is another HFA accumulator and is currently being developed as a new crop for a safe source of HFAs. The mechanisms of HFA synthesis and accumulation have been extensively studied using castor genes and the model plant Arabidopsis. HFAs accumulated to 17% in the seed oil of Arabidopsis expressing a FA hydroxylase gene from castor (RcFAH12), but its seed oil content and plant growth decreased. When RcFAH12 gene was coexpressed with additional castor gene(s) in Arabidopsis, ~30% HFAs were accumulated and the seed oil content and plant growth was almost restored to the wild-type level. Further advancement of our understanding of pathways, genes and regulatory mechanisms underlying synthesis and accumulation of HFAs is essential to developing and implementing effective genetic approaches for enhancing HFA production in oilseeds.

  3. Metabolic engineering of the fungal D-galacturonate pathway for L-ascorbic acid production.

    Science.gov (United States)

    Kuivanen, Joosu; Penttilä, Merja; Richard, Peter

    2015-01-08

    Synthetic L-ascorbic acid (vitamin C) is widely used as a preservative and nutrient in food and pharmaceutical industries. In the current production method, D-glucose is converted to L-ascorbic acid via several biochemical and chemical steps. The main source of L-ascorbic acid in human nutrition is plants. Several alternative metabolic pathways for L-ascorbic acid biosynthesis are known in plants. In one of them, D-galacturonic acid is the precursor. D-Galacturonic acid is also the main monomer in pectin, a plant cell wall polysaccharide. Pectin is abundant in biomass and is readily available from several waste streams from fruit and sugar processing industries. In the present work, we engineered the filamentous fungus Aspergillus niger for the conversion of D-galacturonic acid to L-ascorbic acid. In the generated pathway, the native D-galacturonate reductase activity was utilized while the gene coding for the second enzyme in the fungal D-galacturonic acid pathway, an L-galactonate consuming dehydratase, was deleted. Two heterologous genes coding for enzymes from the plant L-ascorbic acid pathway--L-galactono-1,4-lactone lactonase from Euglena gracilis (EgALase) and L-galactono-1,4-lactone dehydrogenase from Malpighia glabra (MgGALDH)--were introduced into the A. niger strain. Alternatively, an unspecific L-gulono-1,4-lactone lactonase (smp30) from the animal L-ascorbic acid pathway was introduced in the fungal strain instead of the plant L-galactono-1,4-lactone lactonase. In addition, a strain with the production pathway inducible with D-galacturonic acid was generated by using a bidirectional and D-galacturonic acid inducible promoter from the fungus. Even though, the lactonase enzyme activity was not observed in the resulting strains, they were capable of producing L-ascorbic acid from pure D-galacturonic acid or pectin-rich biomass in a consolidated bioprocess. Product titers up to 170 mg/l were achieved. In the current study, an L-ascorbic acid pathway using

  4. Uric acid metabolism in pre-hypertension and the metabolic syndrome.

    Science.gov (United States)

    Rizzo, Manfredi; Obradovic, Milan; Labudovic-Borovic, Milica; Nikolic, Dragana; Montalto, Giuseppe; Rizvi, Ali A; Mikhailidis, Dimitri P; Isenovic, Esma R

    2014-01-01

    In humans uric acid (UA) is the end product of degradation of purines. The handling of UA by the renal system is a complex process which is not fully understood. To date, several urate transporters in the renal proximal tubule have been identified. Among them, urate transporter 1 (URAT1) and a glucose transporter 9 (GLUT9) are considered of greater importance, as potential targets for treatment of hyperuricemia and the potential associated cardio-metabolic risk. Therefore, the recognition of the metabolic pathway of UA and elucidation of occurrence of hyperuricemia may provide important insights about the relationship between UA, pre-hypertension (preHT) and the metabolic syndrome (MetS). We also review the available clinical studies in this field, including experimental studies dealing with the mechanisms of UA transport via different transporters, as well as current treatment options for hyperuricemia in patients with MetS, preHT or cardiovascular risk factors.

  5. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  6. Gene-based mapping and pathway analysis of metabolic traits in dairy cows.

    Directory of Open Access Journals (Sweden)

    Ngoc-Thuy Ha

    Full Text Available The metabolic adaptation of dairy cows during the transition period has been studied intensively in the last decades. However, until now, only few studies have paid attention to the genetic aspects of this process. Here, we present the results of a gene-based mapping and pathway analysis with the measurements of three key metabolites, (1 non-esterified fatty acids (NEFA, (2 beta-hydroxybutyrate (BHBA and (3 glucose, characterizing the metabolic adaptability of dairy cows before and after calving. In contrast to the conventional single-marker approach, we identify 99 significant and biologically sensible genes associated with at least one of the considered phenotypes and thus giving evidence for a genetic basis of the metabolic adaptability. Moreover, our results strongly suggest three pathways involved in the metabolism of steroids and lipids are potential candidates for the adaptive regulation of dairy cows in their early lactation. From our perspective, a closer investigation of our findings will lead to a step forward in understanding the variability in the metabolic adaptability of dairy cows in their early lactation.

  7. Fatty acid metabolism in lambs fed citrus pulp.

    Science.gov (United States)

    Lanza, M; Scerra, M; Bognanno, M; Buccioni, A; Cilione, C; Biondi, L; Priolo, A; Luciano, G

    2015-06-01

    In the present study, we have hypothesized that replacing barley with high proportions of dried citrus pulp in a concentrate-based diet for lambs could increase the intake of unsaturated fatty acids and could reduce the rate of the ruminal biohydrogenation of PUFA, with a consequent improvement of the intramuscular fatty acid composition. To test this hypothesis, 26 Comisana lambs were divided into 3 groups and for 56 d were fed a barley-based concentrate diet (CON; 8 lambs) or 2 diets in which barley was replaced with 24% (CIT24; 9 lambs) or 35% (CIT35; 9 lambs) dried citrus pulp. An overall improvement of the fatty acid composition of LM from lambs fed citrus pulp-containing diets was found. The PUFA/SFA ratio was lower (P citrus pulp could have inhibited the ruminal biohydrogenation of PUFA. This is supported by the fact that regardless of the level of inclusion in the diet, citrus pulp increased the proportion of rumenic acid (P citrus pulp in the diets. Furthermore, the SA/(SA + VA) ratio tended to be lower (P = 0.10) in the ruminal fluid from lambs fed the CIT35 diet compared with that of the CON group. In conclusion, our results support the hypothesis that replacing barley with citrus pulp in the diet of growing lambs improves intramuscular fatty acid composition and underline the need for specific studies to clarify the mechanisms by which feeding citrus pulp affects the fatty acid metabolism in ruminants.

  8. GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

    2011-04-01

    Highlights: {yields}We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. {yields} Deletion of the UGA1 or GAD1 genes extends replicative lifespan. {yields} Addition of GABA to wild-type cultures has no effect on lifespan. {yields} Intracellular GABA levels do not differ in longevity mutants and wild-type cells. {yields} Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for {gamma}-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The {Delta}uga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for {Delta}uga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of {sup 1}H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan

  9. Metabolic Gene Remodeling and Mitochondrial Dysfunction in Failing Right Ventricular Hypertrophy due to Pulmonary Arterial Hypertension

    Science.gov (United States)

    Gomez-Arroyo, Jose; Mizuno, Shiro; Szczepanek, Karol; Van Tassell, Benjamin; Natarajan, Ramesh; dos Remedios, Cristobal G.; Drake, Jennifer I.; Farkas, Laszlo; Kraskauskas, Donatas; Wijesinghe, Dayanjan S.; Chalfant, Charles E.; Bigbee, John; Abbate, Antonio; Lesnefsky, Edward J.; Bogaard, Harm J.; Voelkel, Norbert F.

    2013-01-01

    Background Right ventricular dysfunction (RVD) is the most frequent cause of death in patients with pulmonary arterial hypertension. Whereas abnormal energy substrate utilization has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in RVD remain incomplete. Thus, we sought to characterize metabolic gene expression changes and mitochondrial dysfunction in functional and dysfunctional RV hypertrophy. Methods and Results Two different rat models of RV hypertrophy were studied. The model of RVD (SU5416/hypoxia) exhibited a significantly decreased gene expression of PPAR-gamma coactivator-1 alpha (PGC-1α), PPAR-α and ERR-α. The expression of multiple PCG-1α target genes required for fatty acid oxidation (FAO) was similarly decreased. Decreased PGC-1α expression was also associated with a net loss of mitochondrial protein and oxidative capacity. Reduced mitochondrial number was associated with a downregulation of TFAM and other genes required for mitochondrial biogenesis. Electron microscopy demonstrated that in RVD tissue, mitochondria had abnormal shape and size. Lastly, respirometric analysis demonstrated that mitochondria isolated from RVD-tissue had a significantly reduced ADP-stimulated (state 3) rate for complex I. Conversely, functional RV hypertrophy in the pulmonary artery banding (PAB) model showed normal expression of PGC-1α, whereas the expression of FAO genes was either preserved or unregulated. Moreover, PAB-RV tissue exhibited preserved TFAM expression and mitochondrial respiration despite elevated RV pressure-overload. Conclusions Right ventricular dysfunction, but not functional RV hypertrophy in rats, demonstrates a gene expression profile compatible with a multilevel impairment of fatty acid metabolism and significant mitochondrial dysfunction, partially independent of chronic pressure-overload. PMID:23152488

  10. RNA Sequencing Reveals Xyr1 as a Transcription Factor Regulating Gene Expression beyond Carbohydrate Metabolism

    Directory of Open Access Journals (Sweden)

    Liang Ma

    2016-01-01

    Full Text Available Xyr1 has been demonstrated to be the main transcription activator of (hemicellulases in the well-known cellulase producer Trichoderma reesei. This study comprehensively investigates the genes regulated by Xyr1 through RNA sequencing to produce the transcription profiles of T. reesei Rut-C30 and its xyr1 deletion mutant (Δxyr1, cultured on lignocellulose or glucose. xyr1 deletion resulted in 467 differentially expressed genes on inducing medium. Almost all functional genes involved in (hemicellulose degradation and many transporters belonging to the sugar porter family in the major facilitator superfamily (MFS were downregulated in Δxyr1. By contrast, all differentially expressed protease, lipase, chitinase, some ATP-binding cassette transporters, and heat shock protein-encoding genes were upregulated in Δxyr1. When cultured on glucose, a total of 281 genes were expressed differentially in Δxyr1, most of which were involved in energy, solute transport, lipid, amino acid, and monosaccharide as well as secondary metabolism. Electrophoretic mobility shift assays confirmed that the intracellular β-glucosidase bgl2, the putative nonenzymatic cellulose-attacking gene cip1, the MFS lactose transporter lp, the nmrA-like gene, endo T, the acid protease pepA, and the small heat shock protein hsp23 were probable Xyr1-targets. These results might help elucidate the regulation system for synthesis and secretion of (hemicellulases in T. reesei Rut-C30.

  11. Jacaric acid is rapidly metabolized to conjugated linoleic acid in rats.

    Science.gov (United States)

    Kijima, Ryo; Honma, Taro; Ito, Junya; Yamasaki, Masao; Ikezaki, Aya; Motonaga, Chihiro; Nishiyama, Kazuo; Tsuduki, Tsuyoshi

    2013-01-01

    We have shown previously that jacaric acid (JA; 8c,10t,12c-18:3), which has a conjugated triene system, has a strong anti-tumor effect. However, the characteristics of absorption and metabolism of JA have yet to be determined in vivo, and the details of absorption and metabolism of JA in the small intestine are particularly unclear. This information is required for effective use of JA in humans. Therefore, in this study we examined absorption and metabolism of JA using cannulation of the thoracic duct in rats. Emulsions of two test oils, jacaranda seed oil and tung oil, which contain JA and α-eleostearic acid (α-ESA; 9c,11t,13t-18:3), respectively, were administered to rats and lymph from the thoracic duct was collected over 24 h. We examined the rate of absorption of JA and possible conversion to a conjugated linoleic acid (CLA)containing a conjugated diene system. The positional isomerism of the CLA produced by JA metabolism was determined using gas chromatography-electron impact/mass spectrometry. The rate of absorption and percentage conversion of JA were compared with those of α-ESA. We found that JA is rapidly absorbed and converted to a CLA in rats and that the percentage conversion of JA was lower than that of α-ESA. This is the first report on the absorption and metabolism of JA and this information may be important for application of JA as a functional food.

  12. Effect of acute acid loading on acid-base and calcium metabolism

    DEFF Research Database (Denmark)

    Osther, Palle J

    2006-01-01

    OBJECTIVE: To investigate the acid-base and calcium metabolic responses to acute non-carbonic acid loading in idiopathic calcium stone-formers and healthy males using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h ammonium chloride loading studies were performed in 12...... male recurrent idiopathic calcium stone-formers and 12 matched healthy men using a randomized, placebo-controlled, cross-over design. Arterialized capillary blood, serum and urine were collected hourly for measurement of electrolytes, ionized calcium, magnesium, phosphate, parathyroid hormone and acid-base...... status. Concentrations of non-metabolizable base (NB) and acid (NA) were calculated from measured concentrations of non-metabolizable ions. RESULTS: The extracellular acid-base status in the stone-formers during basal conditions and acid loading was comparable to the levels in the healthy controls...

  13. Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases

    Directory of Open Access Journals (Sweden)

    Floyd H. Chilton

    2014-05-01

    Full Text Available The “modern western” diet (MWD has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6 18 carbon (C18, polyunsaturated fatty acid (PUFA linoleic acid (LA; 18:2n-6, with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS cluster that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD. Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA, CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

  14. Association between serum uric acid level and metabolic syndrome components.

    Science.gov (United States)

    Nejatinamini, Sara; Ataie-Jafari, Asal; Qorbani, Mostafa; Nikoohemat, Shideh; Kelishadi, Roya; Asayesh, Hamid; Hosseini, Saeed

    2015-01-01

    Serum uric acid levels is reported to be associated with a variety of cardiometabolic risk factors; however, its direct association with metabolic syndrome (MetS) remains controversial. Thus, we examined the association of serum uric acid concentrations with the MetS components. MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. This case-control study comprised 101 non-smoking individuals (41 in the MetS group and 60 in the non-MetS group). Blood pressure, fasting plasma glucose, insulin, HOMA-IR, lipid profiles, uric acid, and anthropometric measures were determined, and body composition was assessed by using bioelectrical impedance analysis (BIA). After adjustment for confounding factors, serum uric acid was significantly higher in MetS group than non-MetS group (5.70 ± 1.62 vs 4.97 ± 1.30 mg/dL, respectively, P = 0.001). After controlling for age, sex and body mass index in partial correlation analysis, uric acid was positively correlated with triglycerides, and negatively with HDL-C. In multiple logistic regression analysis, every 1 mg/dl elevation in the serum uric acid level increased the risk of MetS approximately by 2-folds (OR: 2.11, 95 % CI: 1.30-3.41). This study showed that those individuals with MetS have higher uric acid levels; the association of uric acid and MetS components supports that it might be an additional components of MetS.

  15. Omega-3 fatty acids: role in metabolism and cardiovascular disease.

    Science.gov (United States)

    Gerber, Philipp A; Gouni-Berthold, Ioanna; Berneis, Kaspar

    2013-01-01

    The inverse association of cardiovascular risk with intake of omega-3 polyunsaturated fatty acids was suspected early in populations that are known to have a high consumption of fish and fish oil. Subsequent cohort studies confirmed such associations in other populations. Further evidence of possible beneficial effects on metabolism and cardiovascular health was provided by many studies that were able to show specific mechanisms that may underlie these observations. These include improvement of the function of tissues involved in the alterations occurring during the development of obesity and the metabolic syndrome, as adipose tissue, the liver and skeletal muscle. Direct action on the cardiovascular system was not only shown regarding vascular function and the formation of atherosclerotic plaques, but also by providing antiarrhythmic effects on the heart. Data on these effects come from in vitro as well as in vivo studies that were conducted in animal models of disease, in healthy humans and in humans suffering from cardiovascular disease. To define prophylactic as well as treatment options in primary and secondary prevention, large clinical trial assessed the effect of omega-3 polyunsaturated fatty acids on end points as cardiovascular morbidity and mortality. However, so far these trials provided ambiguous data that do allow recommendations regarding the use of omega-3 polyunsaturated fatty acids in higher dosages and beyond the dietary advice of regular fish intake only in few clinical situations, such as severe hypertriglyceridemia.

  16. Metabolic Relations between Methylxanthines and Methyluric Acids in Coffea L.

    Science.gov (United States)

    Petermann, J B; Baumann, T W

    1983-12-01

    Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: [(14)C]theobromine, [(14)C]caffeine, and [(14)C]theacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (O(2), 1,9-thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (O(2),1,7,9-tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4.The collective term ;liberio-excelsoid' introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work.

  17. Regulation of dormancy in barley by blue light and after-ripening: effects on abscisic acid and gibberellin metabolism.

    Science.gov (United States)

    Gubler, Frank; Hughes, Trijntje; Waterhouse, Peter; Jacobsen, John

    2008-06-01

    White light strongly promotes dormancy in freshly harvested cereal grains, whereas dark and after-ripening have the opposite effect. We have analyzed the interaction of light and after-ripening on abscisic acid (ABA) and gibberellin (GA) metabolism genes and dormancy in barley (Hordeum vulgare 'Betzes'). Analysis of gene expression in imbibed barley grains shows that different ABA metabolism genes are targeted by white light and after-ripening. Of the genes examined, white light promotes the expression of an ABA biosynthetic gene, HvNCED1, in embryos. Consistent with this result, enzyme-linked immunosorbent assays show that dormant grains imbibed under white light have higher embryo ABA content than grains imbibed in the dark. After-ripening has no effect on expression of ABA biosynthesis genes, but promotes expression of an ABA catabolism gene (HvABA8'OH1), a GA biosynthetic gene (HvGA3ox2), and a GA catabolic gene (HvGA2ox3) following imbibition. Blue light mimics the effects of white light on germination, ABA levels, and expression of GA and ABA metabolism genes. Red and far-red light have no effect on germination, ABA levels, or HvNCED1. RNA interference experiments in transgenic barley plants support a role of HvABA8'OH1 in dormancy release. Reduced HvABA8'OH1 expression in transgenic HvABA8'OH1 RNAi grains results in higher levels of ABA and increased dormancy compared to nontransgenic grains.

  18. Branched-chain amino acids in metabolic signalling and insulin resistance

    Science.gov (United States)

    Lynch, Christopher J.; Adams, Sean H.

    2015-01-01

    Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM. PMID:25287287

  19. Folic acid, one-carbon metabolism & childhood cancer

    Directory of Open Access Journals (Sweden)

    Nirmalya Roy Moulik

    2017-01-01

    Full Text Available Folate has been studied in relation to many diseases, especially cancer. Although it has been postulated to exert a dual effect on development of cancer, its role remains to be clearly defined. Its effect on cancer is the result of gene-nutrient interaction between the genes in folate metabolic pathway and dietary folate availability; mutations in genes of folate metabolism have been shown to alter individual susceptibility to certain childhood cancers as well as response to cancer chemotherapy. Although mandatory fortification of food items with folate has been initiated in some countries, many countries are yet to adopt this due to concerns about undesired adverse effects of high folate levels on health, especially cancer. However, initial reports suggest that folate fortification has led to reduction in incidence of certain childhood cancers such as neuroblastoma, wilms tumour and leukaemias. Despite studies showing folate depletion during antifolate chemotherapy and higher toxicity of chemotherapy in folate-depleted individuals, folate supplementation during cancer chemotherapy is not routinely recommended. Studies investigating the precise effect of folate supplementation during chemotherapy on both short- and long-term outcomes of cancer are needed to arrive at a consensus guideline.

  20. Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults

    OpenAIRE

    Zhang, Mei-lin; Gao, Yu-xia; Wang, Xuan; Chang, Hong; Huang, Guo-wei

    2012-01-01

    The relation between serum uric acid and metabolic syndrome is observed not only with frank hyperuricemia but also with serum uric acid levels within the normal range. The current ?normal? range set for hyperuricemia often fails to identify patients with potential metabolic disorders. We investigate the association between serum uric acid within the normal range and incident metabolic syndrome risk, and further to determine the optimal cut-off value of serum uric acid for the diagnosis or pre...

  1. Functions of rol genes in plant secondary metabolism.

    Science.gov (United States)

    Bulgakov, Victor P

    2008-01-01

    For a long time, the Agrobacterium rhizogenes rolA, rolB and rolC oncogenes have been considered to be modulators of plant growth and cell differentiation. A new function of the rol genes in plant-Agrobacterium interaction became apparent with the discovery that these genes are potential activators of secondary metabolism in transformed cells from the Solanaceae, Araliaceae, Rubiaceae, Vitaceae and Rosaceae families. In some cases, the activator effect of individual rol genes is sufficient to overcome the inability of cultured plant cells to produce large amounts of secondary metabolites. Here, I summarize the available evidence that shows that genetic transformation by single Agrobacterium rol genes may be used as a powerful tool to manipulate secondary metabolites in cultured plant cells. Although it is known that the rol genes act via transcriptional activation of defense genes, the mechanism of activation is unclear. In this review, evidence is presented to support the hypothesis that the rol genes mediate uncommon signal transduction pathways in plants.

  2. Coordinated and Interactive Expression of Genes of Lipid Metabolism and Inflammation in Adipose Tissue and Liver during Metabolic Overload

    NARCIS (Netherlands)

    Liang, W.; Tonini, G.; Mulder, P.; Kelder, T.; Erk, M. van; Hoek, A.M. van den; Mariman, R.; Wielinga, P.Y.; Baccini, M.; Kooistra, T.; Biggeri, A.; Kleemann, R.

    2013-01-01

    Background:Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT), often accompanied by non-alcoholic fatty liver disease (NAFLD). In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory

  3. Cytochalasins inhibit arachidonic acid metabolism in thrombin-stimulated platelets.

    OpenAIRE

    Siess, W; Lapetina, E G; Cuatrecasas, P

    1982-01-01

    Low concentrations (0.5-1 microM) of cytochalasins inhibit the thrombin-stimulated polymerization of monomeric actin to filamentous actin in platelets. Similar concentrations of cytochalasin B inhibit the formation and metabolism of arachidonic acid in horse platelets stimulated by low concentrations of thrombin (0.1-0.5 unit/ml). However, the release of serotonin is not inhibited by cytochalasin B. Cytochalasins B and D (0.5-1 microM) markedly reduce, in thrombin-stimulated human or horse pl...

  4. Altered Levels of Aroma and Volatiles by Metabolic Engineering of Shikimate Pathway Genes in Tomato Fruits

    Directory of Open Access Journals (Sweden)

    Vered Tzin

    2015-06-01

    Full Text Available The tomato (Solanum lycopersicum fruit is an excellent source of antioxidants, dietary fibers, minerals and vitamins and therefore has been referred to as a “functional food”. Ripe tomato fruits produce a large number of specialized metabolites including volatile organic compounds. These volatiles serve as key components of the tomato fruit flavor, participate in plant pathogen and herbivore defense, and are used to attract seed dispersers. A major class of specialized metabolites is derived from the shikimate pathway followed by aromatic amino acid biosynthesis of phenylalanine, tyrosine and tryptophan. We attempted to modify tomato fruit flavor by overexpressing key regulatory genes in the shikimate pathway. Bacterial genes encoding feedback-insensitive variants of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase (DAHPS; AroG209-9 and bi-functional Chorismate Mutase/Prephenate Dehydratase (CM/PDT; PheA12 were expressed under the control of a fruit-specific promoter. We crossed these transgenes to generate tomato plants expressing both the AroG209 and PheA12 genes. Overexpression of the AroG209-9 gene had a dramatic effect on the overall metabolic profile of the fruit, including enhanced levels of multiple volatile and non-volatile metabolites. In contrast, the PheA12 overexpression line exhibited minor metabolic effects compared to the wild type fruit. Co-expression of both the AroG209-9 and PheA12 genes in tomato resulted overall in a similar metabolic effect to that of expressing only the AroG209-9 gene. However, the aroma ranking attributes of the tomato fruits from PheA12//AroG209-9 were unique and different from those of the lines expressing a single gene, suggesting a contribution of the PheA12 gene to the overall metabolic profile. We suggest that expression of bacterial genes encoding feedback-insensitive enzymes of the shikimate pathway in tomato fruits provides a useful metabolic engineering tool for the modification of

  5. De novo production of the monoterpenoid geranic acid by metabolically engineered Pseudomonas putida.

    Science.gov (United States)

    Mi, Jia; Becher, Daniela; Lubuta, Patrice; Dany, Sarah; Tusch, Kerstin; Schewe, Hendrik; Buchhaupt, Markus; Schrader, Jens

    2014-12-04

    Production of monoterpenoids as valuable chemicals using recombinant microbes is a growing field of interest. Unfortunately, antimicrobial activity of most monoterpenoids hampers a wide application of microorganisms for their production. Strains of Pseudomonas putida, a fast growing and metabolically versatile bacterium, often show an outstanding high tolerance towards organic solvents and other toxic compounds. Therefore, Pseudomonas putida constitutes an attractive alternative host in comparison to conventionally used microorganisms. Here, metabolic engineering of solvent tolerant Pseudomonas putida as a novel microbial cell factory for de novo production of monoterpenoids is reported for the first time, exemplified by geranic acid production from glycerol as carbon source. The monoterpenoic acid is an attractive compound for application in the flavor, fragrance, cosmetics and agro industries. A comparison between Escherichia coli, Saccharomyces cerevisiae and Pseudomonas putida concerning the ability to grow in the presence of geranic acid revealed that the pseudomonad bears a superior resilience compared to the conventionally used microbes. Moreover, Pseudomonas putida DSM 12264 wildtype strain efficiently oxidized externally added geraniol to geranic acid with no further degradation. Omitting external dosage of geraniol but functionally expressing geraniol synthase (GES) from Ocimum basilicum, a first proof-of-concept for de novo biosynthesis of 1.35 mg/L geranic acid in P. putida DSM 12264 was achieved. Doubling the amount of glycerol resulted in twice the amount of product. Co-expression of the six genes of the mevalonate pathway from Myxococcus xanthus to establish flux from acetyl-CoA to the universal terpenoid precursor isopentenylpyrophosphate yielded 36 mg/L geranic acid in shake flask experiments. In the bioreactor, the recombinant strain produced 193 mg/L of geranic acid under fed-batch conditions within 48 h. Metabolic engineering turned Pseudomonas

  6. Metabolic engineering of lactic acid bacteria for the production of nutraceuticals

    NARCIS (Netherlands)

    Hugenholtz, J.; Sybesma, W.; Groot, M.N.; Wisselink, W.; Ladero, V.; Burgess, K.; Sinderen, van D.; Piard, J.C.; Eggink, G.; Smid, E.J.; Savoy, G.; Sesma, F.; Jansen, T.; Hols, P.; Kleerebezem, M.

    2002-01-01

    Lactic acid bacteria display a relatively simple and well-described metabolism where the sugar source is converted mainly to lactic acid. Here we will shortly describe metabolic engineering strategies on the level of sugar metabolism, that lead to either the efficient re-routing of the lactococcal

  7. Comparative Transcriptomics Reveals Jasmonic Acid-Associated Metabolism Related to Cotton Fiber Initiation.

    Directory of Open Access Journals (Sweden)

    Liman Wang

    Full Text Available Analysis of mutants and gene expression patterns provides a powerful approach for investigating genes involved in key stages of plant fiber development. In this study, lintless-fuzzless XinWX and linted-fuzzless XinFLM with a single genetic locus difference for lint were used to identify differentially expressed genes. Scanning electron microscopy showed fiber initiation in XinFLM at 0 days post anthesis (DPA. Fiber transcriptional profiling of the lines at three initiation developmental stages (-1, 0, 1 DPA was performed using an oligonucleotide microarray. Loop comparisons of the differentially expressed genes within and between the lines was carried out, and functional classification and enrichment analysis showed that gene expression patterns during fiber initiation were heavily associated with hormone metabolism, transcription factor regulation, lipid transport, and asparagine biosynthetic processes, as previously reported. Further, four members of the allene-oxide cyclase (AOC family that function in jasmonate biosynthesis were parallel up-regulation in fiber initiation, especially at -1 DPA, compared to other tissues and organs in linted-fuzzed TM-1. Real time-quantitative PCR (RT-qPCR analysis in different fiber mutant lines revealed that AOCs were up-regulated higher at -1 DPA in lintless-fuzzless than that in linted-fuzzless and linted-fuzzed materials, and transcription of the AOCs was increased under jasmonic acid (JA treatment. Expression analysis of JA biosynthesis-associated genes between XinWX and XinFLM showed that they were up-regulated during fiber initiation in the fuzzless-lintless mutant. Taken together, jasmonic acid-associated metabolism was related to cotton fiber initiation. Parallel up-regulation of AOCs expression may be important for normal fiber initiation development, while overproduction of AOCs might disrupt normal fiber development.

  8. Comparative Transcriptomics Reveals Jasmonic Acid-Associated Metabolism Related to Cotton Fiber Initiation.

    Science.gov (United States)

    Wang, Liman; Zhu, Youmin; Hu, Wenjing; Zhang, Xueying; Cai, Caiping; Guo, Wangzhen

    2015-01-01

    Analysis of mutants and gene expression patterns provides a powerful approach for investigating genes involved in key stages of plant fiber development. In this study, lintless-fuzzless XinWX and linted-fuzzless XinFLM with a single genetic locus difference for lint were used to identify differentially expressed genes. Scanning electron microscopy showed fiber initiation in XinFLM at 0 days post anthesis (DPA). Fiber transcriptional profiling of the lines at three initiation developmental stages (-1, 0, 1 DPA) was performed using an oligonucleotide microarray. Loop comparisons of the differentially expressed genes within and between the lines was carried out, and functional classification and enrichment analysis showed that gene expression patterns during fiber initiation were heavily associated with hormone metabolism, transcription factor regulation, lipid transport, and asparagine biosynthetic processes, as previously reported. Further, four members of the allene-oxide cyclase (AOC) family that function in jasmonate biosynthesis were parallel up-regulation in fiber initiation, especially at -1 DPA, compared to other tissues and organs in linted-fuzzed TM-1. Real time-quantitative PCR (RT-qPCR) analysis in different fiber mutant lines revealed that AOCs were up-regulated higher at -1 DPA in lintless-fuzzless than that in linted-fuzzless and linted-fuzzed materials, and transcription of the AOCs was increased under jasmonic acid (JA) treatment. Expression analysis of JA biosynthesis-associated genes between XinWX and XinFLM showed that they were up-regulated during fiber initiation in the fuzzless-lintless mutant. Taken together, jasmonic acid-associated metabolism was related to cotton fiber initiation. Parallel up-regulation of AOCs expression may be important for normal fiber initiation development, while overproduction of AOCs might disrupt normal fiber development.

  9. A Systems Genetics Approach Identifies Gene Regulatory Networks Associated with Fatty Acid Composition in Brassica rapa Seed1

    Science.gov (United States)

    Xiao, Dong; Bucher, Johan; Jin, Mina; Boyle, Kerry; Fobert, Pierre; Maliepaard, Chris

    2016-01-01

    Fatty acids in seeds affect seed germination and seedling vigor, and fatty acid composition determines the quality of seed oil. In this study, quantitative trait locus (QTL) mapping of fatty acid and transcript abundance was integrated with gene network analysis to unravel the genetic regulation of seed fatty acid composition in a Brassica rapa doubled haploid population from a cross between a yellow sarson oil type and a black-seeded pak choi. The distribution of major QTLs for fatty acids showed a relationship with the fatty acid types: linkage group A03 for monounsaturated fatty acids, A04 for saturated fatty acids, and A05 for polyunsaturated fatty acids. Using a genetical genomics approach, expression quantitative trait locus (eQTL) hotspots were found at major fatty acid QTLs on linkage groups A03, A04, A05, and A09. An eQTL-guided gene coexpression network of lipid metabolism-related genes showed major hubs at the genes BrPLA2-ALPHA, BrWD-40, a number of seed storage protein genes, and the transcription factor BrMD-2, suggesting essential roles for these genes in lipid metabolism. Three subnetworks were extracted for the economically important and most abundant fatty acids erucic, oleic, linoleic, and linolenic acids. Network analysis, combined with comparison of the genome positions of cis- or trans-eQTLs with fatty acid QTLs, allowed the identification of candidate genes for genetic regulation of these fatty acids. The generated insights in the genetic architecture of fatty acid composition and the underlying complex gene regulatory networks in B. rapa seeds are discussed. PMID:26518343

  10. A Systems Genetics Approach Identifies Gene Regulatory Networks Associated with Fatty Acid Composition in Brassica rapa Seed.

    Science.gov (United States)

    Basnet, Ram Kumar; Del Carpio, Dunia Pino; Xiao, Dong; Bucher, Johan; Jin, Mina; Boyle, Kerry; Fobert, Pierre; Visser, Richard G F; Maliepaard, Chris; Bonnema, Guusje

    2016-01-01

    Fatty acids in seeds affect seed germination and seedling vigor, and fatty acid composition determines the quality of seed oil. In this study, quantitative trait locus (QTL) mapping of fatty acid and transcript abundance was integrated with gene network analysis to unravel the genetic regulation of seed fatty acid composition in a Brassica rapa doubled haploid population from a cross between a yellow sarson oil type and a black-seeded pak choi. The distribution of major QTLs for fatty acids showed a relationship with the fatty acid types: linkage group A03 for monounsaturated fatty acids, A04 for saturated fatty acids, and A05 for polyunsaturated fatty acids. Using a genetical genomics approach, expression quantitative trait locus (eQTL) hotspots were found at major fatty acid QTLs on linkage groups A03, A04, A05, and A09. An eQTL-guided gene coexpression network of lipid metabolism-related genes showed major hubs at the genes BrPLA2-ALPHA, BrWD-40, a number of seed storage protein genes, and the transcription factor BrMD-2, suggesting essential roles for these genes in lipid metabolism. Three subnetworks were extracted for the economically important and most abundant fatty acids erucic, oleic, linoleic, and linolenic acids. Network analysis, combined with comparison of the genome positions of cis- or trans-eQTLs with fatty acid QTLs, allowed the identification of candidate genes for genetic regulation of these fatty acids. The generated insights in the genetic architecture of fatty acid composition and the underlying complex gene regulatory networks in B. rapa seeds are discussed. © 2016 American Society of Plant Biologists. All Rights Reserved.

  11. Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

    Science.gov (United States)

    Ljungdahl, Per O.; Daignan-Fornier, Bertrand

    2012-01-01

    Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear. PMID:22419079

  12. Ascorbate metabolism and the developmental demand for tartaric and oxalic acids in ripening grape berries

    Directory of Open Access Journals (Sweden)

    Soole Kathleen L

    2009-12-01

    Full Text Available Abstract Background Fresh fruits are well accepted as a good source of the dietary antioxidant ascorbic acid (Asc, Vitamin C. However, fruits such as grapes do not accumulate exceptionally high quantities of Asc. Grapes, unlike most other cultivated fruits do however use Asc as a precursor for the synthesis of both oxalic (OA and tartaric acids (TA. TA is a commercially important product in the wine industry and due to its acidifying effect on crushed juice it can influence the organoleptic properties of the wine. Despite the interest in Asc accumulation in fruits, little is known about the mechanisms whereby Asc concentration is regulated. The purpose of this study was to gain insights into Asc metabolism in wine grapes (Vitis vinifera c.v. Shiraz. and thus ascertain whether the developmental demand for TA and OA synthesis influences Asc accumulation in the berry. Results We provide evidence for developmentally differentiated up-regulation of Asc biosynthetic pathways and subsequent fluctuations in Asc, TA and OA accumulation. Rapid accumulation of Asc and a low Asc to dehydroascorbate (DHA ratio in young berries was co-ordinated with up-regulation of three of the primary Asc biosynthetic (Smirnoff-Wheeler pathway genes. Immature berries synthesised Asc in-situ from the primary pathway precursors D-mannose and L-galactose. Immature berries also accumulated TA in early berry development in co-ordination with up-regulation of a TA biosynthetic gene. In contrast, ripe berries have up-regulated expression of the alternative Asc biosynthetic pathway gene D-galacturonic acid reductase with only residual expression of Smirnoff-Wheeler Asc biosynthetic pathway genes and of the TA biosynthetic gene. The ripening phase was further associated with up-regulation of Asc recycling genes, a secondary phase of increased accumulation of Asc and an increase in the Asc to DHA ratio. Conclusion We demonstrate strong developmental regulation of Asc biosynthetic

  13. Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

    Science.gov (United States)

    Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

    2010-01-01

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels. PMID:20093359

  14. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    Science.gov (United States)

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  15. Nutritional and Hormonal Regulation of Citrate and Carnitine/Acylcarnitine Transporters: Two Mitochondrial Carriers Involved in Fatty Acid Metabolism

    Directory of Open Access Journals (Sweden)

    Anna M. Giudetti

    2016-05-01

    Full Text Available The transport of solutes across the inner mitochondrial membrane is catalyzed by a family of nuclear-encoded membrane-embedded proteins called mitochondrial carriers (MCs. The citrate carrier (CiC and the carnitine/acylcarnitine transporter (CACT are two members of the MCs family involved in fatty acid metabolism. By conveying acetyl-coenzyme A, in the form of citrate, from the mitochondria to the cytosol, CiC contributes to fatty acid and cholesterol synthesis; CACT allows fatty acid oxidation, transporting cytosolic fatty acids, in the form of acylcarnitines, into the mitochondrial matrix. Fatty acid synthesis and oxidation are inversely regulated so that when fatty acid synthesis is activated, the catabolism of fatty acids is turned-off. Malonyl-CoA, produced by acetyl-coenzyme A carboxylase, a key enzyme of cytosolic fatty acid synthesis, represents a regulator of both metabolic pathways. CiC and CACT activity and expression are regulated by different nutritional and hormonal conditions. Defects in the corresponding genes have been directly linked to various human diseases. This review will assess the current understanding of CiC and CACT regulation; underlining their roles in physio-pathological conditions. Emphasis will be placed on the molecular basis of the regulation of CiC and CACT associated with fatty acid metabolism.

  16. Metabolic Interactions between Vitamin A and Conjugated Linoleic Acid

    Directory of Open Access Journals (Sweden)

    Gianfranca Carta

    2014-03-01

    Full Text Available Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4. However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

  17. Absorption and metabolism of benzoic acid in growing pigs

    DEFF Research Database (Denmark)

    Kristensen, N B; Nørgaard, J V; Wamberg, S

    2009-01-01

    Dietary benzoic acid (BA) supplementation causes a pronounced reduction in urinary pH but only small changes in blood pH. The present study aimed to investigate the portal absorption profile, hepatic metabolism of BA, and renal excretion of hippuric acid (HA) underlying the relatively small impact......) or BA supplementation (B; control diet + 1% BA top-dressed). Feed intake was restricted to 3.6% of BW and the ration divided into 3 equally sized meals offered at 8-h intervals. Blood pH (7.465 and 7.486 ± 0.004) and urinary pH (4.99 and 7.01 ± 0.09) were less (P = 0.03 and P

  18. Principal transcriptional regulation and genome-wide system interactions of the Asp-family and aromatic amino acid networks of amino acid metabolism in plants.

    Science.gov (United States)

    Less, Hadar; Angelovici, Ruthie; Tzin, Vered; Galili, Gad

    2010-10-01

    Amino acid metabolism is among the most important and best recognized networks within biological systems. In plants, amino acids serve multiple functions associated with growth. Besides their function in protein synthesis, the amino acids are also catabolized into energy-associated metabolites as well we into numerous secondary metabolites, which are essential for plant growth and response to various stresses. Despite the central importance of amino acids in plants growth, elucidation of the regulation of amino acid metabolism within the context of the entire system, particularly transcriptional regulation, is still in its infancy. The different amino acids are synthesized by a number of distinct metabolic networks, which are expected to possess regulatory cross interactions between them for proper coordination of their interactive functions, such as incorporation into proteins. Yet, individual amino acid metabolic networks are also expected to differentially cross interact with various genome-wide gene expression programs and metabolic networks, in respect to their functions as precursors for various metabolites with distinct functions. In the present review, we discuss our recent genomics, metabolic and bioinformatics studies, which were aimed at addressing these questions, focusing mainly on the Asp-family metabolic network as the main example and also comparing it to the aromatic amino acids metabolic network as a second example (Angelovici et al. in Plant Physiol 151:2058-2072, 2009; Less and Galili in BMC Syst Biol 3:14, 2009; Tzin et al. in Plant J 60:156-167, 2009). Our focus on these two networks is because of the followings: (i) both networks are central to plant metabolism and growth and are also precursors for a wide range of primary and secondary metabolites that are indispensable to plant growth; (ii) the amino acids produced by these two networks are also essential to the nutrition and health of human and farm animals; and (iii) both networks contain

  19. Centimetre-scale vertical variability of phenoxy acid herbicide mineralization potential in aquifer sediment relates to the abundance of tfdA genes

    DEFF Research Database (Denmark)

    Pazarbasi, Meric Batioglu; Bælum, Jacob; Johnsen, Anders R.

    2012-01-01

    are known to be involved in the metabolism of phenoxy acid herbicides. tfdA class III gene copy number was approximately 100-fold greater in samples able to mineralize MCPA than in samples able to mineralize 2,4-D, suggesting that tfdA class III gene plays a greater role in the metabolism of MCPA than of 2...

  20. Noise propagation in synthetic gene circuits for metabolic control.

    Science.gov (United States)

    Oyarzún, Diego A; Lugagne, Jean-Baptiste; Stan, Guy-Bart V

    2015-02-20

    Dynamic control of enzyme expression can be an effective strategy to engineer robust metabolic pathways. It allows a synthetic pathway to self-regulate in response to changes in bioreactor conditions or the metabolic state of the host. The implementation of this regulatory strategy requires gene circuits that couple metabolic signals with the genetic machinery, which is known to be noisy and one of the main sources of cell-to-cell variability. One of the unexplored design aspects of these circuits is the propagation of biochemical noise between enzyme expression and pathway activity. In this article, we quantify the impact of a synthetic feedback circuit on the noise in a metabolic product in order to propose design criteria to reduce cell-to-cell variability. We consider a stochastic model of a catalytic reaction under negative feedback from the product to enzyme expression. On the basis of stochastic simulations and analysis, we show that, depending on the repression strength and promoter strength, transcriptional repression of enzyme expression can amplify or attenuate the noise in the number of product molecules. We obtain analytic estimates for the metabolic noise as a function of the model parameters and show that noise amplification/attenuation is a structural property of the model. We derive an analytic condition on the parameters that lead to attenuation of metabolic noise, suggesting that a higher promoter sensitivity enlarges the parameter design space. In the theoretical case of a switch-like promoter, our analysis reveals that the ability of the circuit to attenuate noise is subject to a trade-off between the repression strength and promoter strength.

  1. Dietary trans-fatty acids and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Zdzisław Kochan

    2010-12-01

    Full Text Available Trans-fatty acids (TFAs, products of partial hydrogenation of vegetable oils, have become more prevalent in our diet since the 1960s, when they replaced animal fats. TFAs also occur naturally in meat and dairy products from ruminants. There is growing evidence that dietary trans-fatty acids may increase the risk of metabolic syndrome. Several studies have demonstrated adverse effects of TFAs on plasma lipids and lipoproteins. In dietary trials, trans-fatty acids have been shown to raise the total cholesterol/HDL cholesterol ratio and Lp(a levels in blood. Moreover, a high intake of TFAs has been associated with an increased risk of coronary heart disease. Prospective cohort studies have shown that dietary trans-fatty acids promote abdominal obesity and weight gain. In addition, it appears that TFA consumption may be associated with the development of insulin resistance and type 2 diabetes. The documented adverse health effects of TFAs emphasise the importance of efforts to reduce the content of partially hydrogenated vegetable oils in foods.

  2. The genes and enzymes of the carotenoid metabolic pathway in Vitis vinifera L.

    Science.gov (United States)

    2012-01-01

    Background Carotenoids are a heterogeneous group of plant isoprenoids primarily involved in photosynthesis. In plants the cleavage of carotenoids leads to the formation of the phytohormones abscisic acid and strigolactone, and C13-norisoprenoids involved in the characteristic flavour and aroma compounds in flowers and fruits and are of specific importance in the varietal character of grapes and wine. This work extends the previous reports of carotenoid gene expression and photosynthetic pigment analysis by providing an up-to-date pathway analysis and an important framework for the analysis of carotenoid metabolic pathways in grapevine. Results Comparative genomics was used to identify 42 genes putatively involved in carotenoid biosynthesis/catabolism in grapevine. The genes are distributed on 16 of the 19 chromosomes and have been localised to the physical map of the heterozygous ENTAV115 grapevine sequence. Nine of the genes occur as single copies whereas the rest of the carotenoid metabolic genes have more than one paralogue. The cDNA copies of eleven corresponding genes from Vitis vinifera L. cv. Pinotage were characterised, and four where shown to be functional. Microarrays provided expression profiles of 39 accessions in the metabolic pathway during three berry developmental stages in Sauvignon blanc, whereas an optimised HPLC analysis provided the concentrations of individual carotenoids. This provides evidence of the functioning of the lutein epoxide cycle and the respective genes in grapevine. Similarly, orthologues of genes leading to the formation of strigolactone involved in shoot branching inhibition were identified: CCD7, CCD8 and MAX1. Moreover, the isoforms typically have different expression patterns, confirming the complex regulation of the pathway. Of particular interest is the expression pattern of the three VvNCEDs: Our results support previous findings that VvNCED3 is likely the isoform linked to ABA content in berries. Conclusions The

  3. A Balanced Tissue Composition Reveals New Metabolic and Gene Expression Markers in Prostate Cancer.

    Directory of Open Access Journals (Sweden)

    May-Britt Tessem

    Full Text Available Molecular analysis of patient tissue samples is essential to characterize the in vivo variability in human cancers which are not accessible in cell-lines or animal models. This applies particularly to studies of tumor metabolism. The challenge is, however, the complex mixture of various tissue types within each sample, such as benign epithelium, stroma and cancer tissue, which can introduce systematic biases when cancers are compared to normal samples. In this study we apply a simple strategy to remove such biases using sample selections where the average content of stroma tissue is balanced between the sample groups. The strategy is applied to a prostate cancer patient cohort where data from MR spectroscopy and gene expression have been collected from and integrated on the exact same tissue samples. We reveal in vivo changes in cancer-relevant metabolic pathways which are otherwise hidden in the data due to tissue confounding. In particular, lowered levels of putrescine are connected to increased expression of SRM, reduced levels of citrate are attributed to upregulation of genes promoting fatty acid synthesis, and increased succinate levels coincide with reduced expression of SUCLA2 and SDHD. In addition, the strategy also highlights important metabolic differences between the stroma, epithelium and prostate cancer. These results show that important in vivo metabolic features of cancer can be revealed from patient data only if the heterogeneous tissue composition is properly accounted for in the analysis.

  4. Engineering Escherichia coli with acrylate pathway genes for propionic acid synthesis and its impact on mixed-acid fermentation.

    Science.gov (United States)

    Kandasamy, Vijayalakshmi; Vaidyanathan, Hema; Djurdjevic, Ivana; Jayamani, Elamparithi; Ramachandran, K B; Buckel, Wolfgang; Jayaraman, Guhan; Ramalingam, Subramanian

    2013-02-01

    Fermentation-derived products are in greater demand to meet the increasing global market as well as to overcome environmental problems. In this work, Escherichia coli has been metabolically engineered with acrylate pathway genes from Clostridium propionicum for the conversion of D-lactic acid to propionic acid. The introduced synthetic pathway consisted of seven genes encoding the enzymes propionate CoA-transferase (Pct), lactoyl-CoA dehydratase (Lcd) and acryloyl-CoA reductase (Acr). The engineered strain synthesised propionic acid at a concentration of 3.7 ± 0.2 mM upon fermentation on glucose. This low production level could be attributed to the low activity of the recombinant enzymes in particular the rate-limiting enzyme, Acr. Interestingly, the recombinant pathway caused an increased lactate production in E. coli with a yield of 1.9 mol/mol of glucose consumed along with a decrease in other by-products. Down-regulation of the pfl (pyruvate formate lyase) genes and a possible inhibition of Pfl activity by the acrylate pathway intermediate, acryloyl-CoA, could have reduced carbon flow to the Pfl pathway with a concomitant increase in lactate production. This study reports a novel way of synthesising propionic acid by employing a non-native, user-friendly organism through metabolic engineering.

  5. Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity.

    Science.gov (United States)

    Walle, Paula; Takkunen, Markus; Männistö, Ville; Vaittinen, Maija; Lankinen, Maria; Kärjä, Vesa; Käkelä, Pirjo; Ågren, Jyrki; Tiainen, Mika; Schwab, Ursula; Kuusisto, Johanna; Laakso, Markku; Pihlajamäki, Jussi

    2016-05-01

    Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown. Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease. Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, p<0.002) and stearoyl-CoA desaturase 1 (SCD1, p<0.002) and lower activity of delta-5 desaturase (D5D, p<0.002) when compared to individuals with normal liver. Estimated activities of D5D, D6D and SCD1 correlated positively between liver and serum indicating that serum estimates reflected liver metabolism. Accordingly, NASH was associated with higher hepatic mRNA expression of corresponding genes FADS1, FADS2 and SCD. Finally, differences in FA metabolism that associated with NASH in obese individuals were also associated with high ALT in the METSIM Study. We demonstrated alterations in FA metabolism and endogenous desaturase activities that associate with NASH, independent of obesity and diet. This suggests that changes in endogenous FA metabolism are related to NASH and that they may contribute to the progression of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Association of an ACSL1 gene variant with polyunsaturated fatty acids in bovine skeletal muscle.

    Science.gov (United States)

    Widmann, Philipp; Nuernberg, Karin; Kuehn, Christa; Weikard, Rosemarie

    2011-11-11

    The intramuscular fat deposition and the fatty acid profiles of beef affect meat quality. High proportions of unsaturated fatty acids are related to beef flavor and are beneficial for the nutritional value of meat. Moreover, a variety of clinical and epidemiologic studies showed that particularly long-chain omega-3 fatty acids from animal sources have a positive impact on human health and disease. To screen for genetic factors affecting fatty acid profiles in beef, we initially performed a microsatellite-based genome scan in a F(2) Charolais × German Holstein resource population and identified a quantitative trait locus (QTL) for fatty acid composition in a region on bovine chromosome 27 where previously QTL affecting marbling score had been detected in beef cattle populations. The long-chain acyl-CoA synthetase 1 (ACSL1) gene was identified as the most plausible functional and positional candidate gene in the QTL interval due to its direct impact on fatty acid metabolism and its position in the QTL interval. ACSL1 is necessary for synthesis of long-chain acyl-CoA esters, fatty acid degradation and phospholipid remodeling. We validated the genomic annotation of the bovine ACSL1 gene by in silico comparative sequence analysis and experimental verification. Re-sequencing of the complete coding, exon-flanking intronic sequences, 3' untranslated region (3'UTR) and partial promoter region of the ACSL1 gene revealed three synonymous mutations in exons 6, 7, and 20, six noncoding intronic gene variants, six polymorphisms in the promoter region, and four variants in the 3' UTR region. The association analysis identified the gene variant in intron 5 of the ACSL1 gene (c.481-233A>G) to be significantly associated with the relative content of distinct fractions and ratios of fatty acids (e.g., n-3 fatty acids, polyunsaturated, n-3 long-chain polyunsaturated fatty acids, trans vaccenic acid) in skeletal muscle. A tentative association of the ACSL1 gene variant with

  7. Association of an ACSL1 gene variant with polyunsaturated fatty acids in bovine skeletal muscle

    Directory of Open Access Journals (Sweden)

    Widmann Philipp

    2011-11-01

    Full Text Available Abstract Background The intramuscular fat deposition and the fatty acid profiles of beef affect meat quality. High proportions of unsaturated fatty acids are related to beef flavor and are beneficial for the nutritional value of meat. Moreover, a variety of clinical and epidemiologic studies showed that particularly long-chain omega-3 fatty acids from animal sources have a positive impact on human health and disease. Results To screen for genetic factors affecting fatty acid profiles in beef, we initially performed a microsatellite-based genome scan in a F2 Charolais × German Holstein resource population and identified a quantitative trait locus (QTL for fatty acid composition in a region on bovine chromosome 27 where previously QTL affecting marbling score had been detected in beef cattle populations. The long-chain acyl-CoA synthetase 1 (ACSL1 gene was identified as the most plausible functional and positional candidate gene in the QTL interval due to its direct impact on fatty acid metabolism and its position in the QTL interval. ACSL1 is necessary for synthesis of long-chain acyl-CoA esters, fatty acid degradation and phospholipid remodeling. We validated the genomic annotation of the bovine ACSL1 gene by in silico comparative sequence analysis and experimental verification. Re-sequencing of the complete coding, exon-flanking intronic sequences, 3' untranslated region (3'UTR and partial promoter region of the ACSL1 gene revealed three synonymous mutations in exons 6, 7, and 20, six noncoding intronic gene variants, six polymorphisms in the promoter region, and four variants in the 3' UTR region. The association analysis identified the gene variant in intron 5 of the ACSL1 gene (c.481-233A>G to be significantly associated with the relative content of distinct fractions and ratios of fatty acids (e.g., n-3 fatty acids, polyunsaturated, n-3 long-chain polyunsaturated fatty acids, trans vaccenic acid in skeletal muscle. A tentative association

  8. (Im) Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

    NARCIS (Netherlands)

    He, F.; Fromion, V.; Westerhoff, H.V.

    2013-01-01

    Background: Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a

  9. Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction

    NARCIS (Netherlands)

    van Straten, Esther M. E.; Bloks, Vincent W.; van Dijk, Theo H.; Baller, Julius F. W.; Huijkman, Nicolette C. A.; Kuipers, Irma; Verkade, Henkjan J.; Plosch, Torsten

    Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome. Objective: We

  10. The decarboxylation of the weak-acid preservative, sorbic acid, is encoded by linked genes in Aspergillus spp.

    Science.gov (United States)

    Plumridge, Andrew; Melin, Petter; Stratford, Malcolm; Novodvorska, Michaela; Shunburne, Lee; Dyer, Paul S; Roubos, Johannes A; Menke, Hildegard; Stark, Jacques; Stam, Hein; Archer, David B

    2010-08-01

    The ability to resist anti-microbial compounds is of key evolutionary benefit to microorganisms. Aspergillus niger has previously been shown to require the activity of a phenylacrylic acid decarboxylase (encoded by padA1) for the decarboxylation of the weak-acid preservative sorbic acid (2,4-hexadienoic acid) to 1,3-pentadiene. It is now shown that this decarboxylation process also requires the activity of a putative 4-hydroxybenzoic acid (3-octaprenyl-4-hydroxybenzoic acid) decarboxylase, encoded by a gene termed ohbA1, and a putative transcription factor, sorbic acid decarboxylase regulator, encoded by sdrA. The padA1,ohbA1 and sdrA genes are in close proximity to each other on chromosome 6 in the A. niger genome and further bioinformatic analysis revealed conserved synteny at this locus in several Aspergillus species and other ascomycete fungi indicating clustering of metabolic function. This cluster is absent from the genomes of A. fumigatus and A. clavatus and, as a consequence, neither species is capable of decarboxylating sorbic acid. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

    Directory of Open Access Journals (Sweden)

    Andrew W Bergen

    Full Text Available The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine, has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3. Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

  12. Effects of achilline on lipid metabolism gene expression in cell culture

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    A. V. Ratkin

    2016-01-01

    Full Text Available Objective. Evaluation in vitro of the mechanisms of the hypolipidemic effect of sesquiterpene γ-lactone achilline in the hepatoma tissue culture (HTC.Materials and methods.The influence of sesquiterpene γ-lactone achilline and gemfibrozil (comparison drug on the viability, lipid content and expression of key genes of lipid metabolism in the hepatoma tissue culture. The lipid content was assessed by fluorescent method with the vital dye Nile Red, the cell viability was assessed using MTT assay.Results. Cultivation of of cell cultures of rat’s hepatoma cell line HTC for 48 h with achilline in a concentration of from 0.25 to 1.0 mm and gemfibrozil from 0,25 to 0,5 mm did not change cell viability compared to control. In these same concentrations of the test substance reduced the lipid content in the cells, assessed by fluorescent method with the vital dye Nile Red. To study the mechanism of hypolipidemicaction of achillinedetermined the expression of key genes of lipid metabolism in cell culture lines HTC. The possible mechanism of hypolipidemic action of achilline can be attributed to the increased transport and oxidation of long-chain fatty acids in mitochondria, as evidenced by the increase in the gene expression of carnitine-palmitoyltransferase 2 (Cpt2. The decrease in cholesterol level may be due to increased synthesis of bile acids from cholesterol, due to increased gene expression of 7-alphahydroxylase (Cyp7a1. Conclusion. In cell cultures of rat’s hepatoma cell line HTC sesquiterpene γ-lactone achilline reduces the accumulation of lipids in cells, as evidenced by the decrease in the fluorescence of Nile Red, increased gene expression of the carnitine-palmitoyltransferase 2 (Cpt2 gene and 7-alpha-hydroxylase (Cyp7a1.

  13. Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

    OpenAIRE

    Herman, Mark A; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

    2010-01-01

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent obse...

  14. Suppression of a thermosensitive zipA cell division mutant by altering amino acid metabolism.

    Science.gov (United States)

    Mendoza, Daniel Vega; Margolin, William

    2017-10-23

    ZipA is essential for cell division in Escherichia coli, acting early in the process to anchor polymers of FtsZ to the cytoplasmic membrane. Along with FtsA, FtsZ and ZipA form a proto-ring at midcell that recruits additional proteins to eventually build the division septum. Cells carrying the thermosensitive zipA1 allele divide fairly normally at 30°C in rich medium but cease dividing at temperatures above 34°C, forming long filaments. In a search for suppressors of zipA1, we found that deletions of specific genes involved in amino acid biosynthesis could partially cell rescue growth and division at 34°C or 37°C, but not at 42°C. Notably, although a diverse group of amino acid biosynthetic gene deletions could partially rescue growth of zipA1 cells at 34°C, only deletions of genes related to the biosynthesis of threonine, glycine, serine and methionine could rescue at 37°C. Adding exogenous pyridoxal 5-phosphate (PLP), a cofactor for many of the enzymes affected by this study, partially suppressed zipA1 thermosensitivity. For many of the deletions, PLP had an additive rescuing effect on zipA1 Moreover, added PLP partially suppressed the thermosensitivity of ftsQ and ftsK mutants, weakly suppressed an ftsI mutant, but failed to suppress ftsA or ftsZ thermosensitive mutants. Along with the ability of a deletion of metC to partially suppress ftsK, our results suggest that perturbations of amino acid metabolic pathways, particularly those that redirect the flow of carbon away from synthesis of threonine, glycine, or methionine, are able to partially rescue some cell division defects.IMPORTANCE Cell division of bacteria such as Escherichia coli is essential for their successful colonization. It is becoming increasingly clear that nutritional status and central metabolism can affect bacterial size and shape; for example, a metabolic enzyme (OpgH) can moonlight as a regulator of FtsZ, an essential cell division protein. Here, we demonstrate a link between amino

  15. Effects of a 3 strain -based direct-fed microbial and dietary fiber concentration on growth performance and expression of genes related to absorption and metabolism of volatile fatty acids in weanling pigs.

    Science.gov (United States)

    Jaworski, N W; Owusu-Asiedu, A; Walsh, M C; McCann, J C; Loor, J J; Stein, H H

    2017-01-01

    Effects of a -based direct-fed microbial (DFM) on growth performance, plasma tumor necrosis factor ɑ (TNFɑ), relative gene expression, and intestinal VFA concentrations in weanling pigs fed low- or high-fiber diets were evaluated. Two hundred pigs (initial BW: 6.31 ± 0.73 kg) were allotted to 1 of 4 dietary treatments (5 pigs per pen and 10 pens per treatment). Treatments were arranged in a 2 × 2 factorial design with 2 diet types [low-fiber (LF) or high-fiber (HF)] and 2 concentrations of DFM (0 or 60 g DFM/t of feed). The DFM contained 1.5 × 10 cfu/g and was obtained from Danisco Animal Nutrition-DuPont Industrial Biosciences, Marlborough, UK. Phase 1 diets were fed for 2 wk post-weaning and phase 2 diets were fed over the following 29 d. Low fiber diets contained corn and soybean meal as main ingredients and HF diets contained corn, soybean meal, corn distillers dried grains with solubles (7.5 and 15.0% in phase 1 and 2, respectively), and wheat middlings (10.0%). Pigs and feed were weighed at the start and at the end of each phase, and ADG, ADFI, and G:F were calculated. At the conclusion of phase 2, blood was collected from 1 pig per pen and 1 pig per pen was sacrificed. Cecum and rectum contents were analyzed for VFA, and tissue samples were collected from the ileum, cecum, rectum, and liver to determine expression of genes related to absorption and metabolism of VFA using quantitative reverse transcription-PCR. Results indicated that feeding HF diets reduced ( ≤ 0.05) ADFI and ADG of pigs compared with feeding LF diets. Pigs fed DFM diets had improved ( ≤ 0.05) G:F compared with pigs fed non-DFM diets. Pigs fed LF diets had greater ( ≤ 0.05) BW at the end of phase 2 compared with pigs fed HF diets. The concentration of VFA in rectum contents was greater ( ≤ 0.05) in pigs fed LF diets than in pigs fed HF diets. The expression of in the rectum of pigs fed HF diets was greater ( ≤ 0.05) than for pigs fed LF diets, and pigs fed DFM

  16. One carbon metabolism in anaerobic bacteria: Regulation of carbon and electron flow during organic acid production

    Energy Technology Data Exchange (ETDEWEB)

    Zeikus, J.G.; Jain, M.

    1993-12-31

    The project deals with understanding the fundamental biochemical mechanisms that physiologically control and regulate carbon and electron flow in anaerobic chemosynthetic bacteria that couple metabolism of single carbon compounds and hydrogen to the production of organic acids (formic, acetic, butyric, and succinic) or methane. The authors compare the regulation of carbon dioxide and hydrogen metabolism by fermentation, enzyme, and electron carrier analysis using Butyribacterium methylotrophicum, Anaeroblospirillum succiniciproducens, Methanosarcina barkeri, and a newly isolated tri-culture composed of a syntrophic butyrate degrader strain IB, Methanosarcina mazei and Methanobacterium formicicum as model systems. To understand the regulation of hydrogen metabolism during butyrate production or acetate degradation, hydrogenase activity in B. methylotrophicum or M. barkeri is measured in relation to growth substrate and pH; hydrogenase is purified and characterized to investigate number of hydrogenases; their localization and functions; and, their sequences are determined. To understand the mechanism for catabolic CO{sub 2} fixation to succinate the PEP carboxykinase enzyme and gene of A. succiniciproducens are purified and characterized. Genetically engineered strains of Escherichia coli containing the phosphoenolpyruvate (PEP) carboxykinase gene are examined for their ability to produce succinate in high yield. To understand the mechanism of fatty acid degradation by syntrophic acetogens during mixed culture methanogenesis formate and hydrogen production are characterized by radio tracer studies. It is intended that these studies provide strategies to improve anaerobic fermentations used for the production of organic acids or methane and, new basic understanding on catabolic CO{sub 2} fixation mechanisms and on the function of hydrogenase in anaerobic bacteria.

  17. Gene coexpression network analysis of fruit transcriptomes uncovers a possible mechanistically distinct class of sugar/acid ratio-associated genes in sweet orange.

    Science.gov (United States)

    Qiao, Liang; Cao, Minghao; Zheng, Jian; Zhao, Yihong; Zheng, Zhi-Liang

    2017-10-30

    The ratio of sugars to organic acids, two of the major metabolites in fleshy fruits, has been considered the most important contributor to fruit sweetness. Although accumulation of sugars and acids have been extensively studied, whether plants evolve a mechanism to maintain, sense or respond to the fruit sugar/acid ratio remains a mystery. In a prior study, we used an integrated systems biology tool to identify a group of 39 acid-associated genes from the fruit transcriptomes in four sweet orange varieties (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). We reanalyzed the prior sweet orange fruit transcriptome data, leading to the identification of 72 genes highly correlated with the fruit sugar/acid ratio. The majority of these sugar/acid ratio-related genes are predicted to be involved in regulatory functions such as transport, signaling and transcription or encode enzymes involved in metabolism. Surprisingly, only three of these sugar/acid ratio-correlated genes are weakly correlated with sugar level and none of them overlaps with the acid-associated genes. Weighted Gene Coexpression Network Analysis (WGCNA) has revealed that these genes belong to four modules, Blue, Grey, Brown and Turquoise, with the former two modules being unique to the sugar/acid ratio control. Our results indicate that orange fruits contain a possible mechanistically distinct class of genes that may potentially be involved in maintaining fruit sugar/acid ratios and/or responding to the cellular sugar/acid ratio status. Therefore, our analysis of orange transcriptomes provides an intriguing insight into the potentially novel genetic or molecular mechanisms controlling the sugar/acid ratio in fruits.

  18. [Metabolic syndrome reversion by polyunsaturated fatty acids ingestion].

    Science.gov (United States)

    Campos Mondragón, Martha Gabriela; Oliart Ros, Rosa María; Martínez Martinez, Angélica; Méndez Machado, Gustavo Francisco; Angulo Guerrero, Jesús Ofelia

    2013-12-21

    Metabolic syndrome (MS) frequency is growing and diet has an important influence on its evolution. Our objective was to study the effect of 3 sources of polyunsaturated fatty acids on MS parameters in humans. The MS was diagnosed according to the International Diabetes Federation. Three groups of individuals (n=15/group) were quasi-randomly assigned to one of the following treatments during 6 weeks: a) 1.8 g/d n-3 (1.08g eicosapentoaenoic acid+0.72 g docosahexaenoic acid); b) 2.0 g/d conjugated linoleic acid (CLA, 50:50, cis9:trans11, trans10:cis12), and c) 40 g/d walnut. The clinical and biochemical parameters were evaluated at the beginning and the end of the essay. In the group with n-3 the triglycerides level decreased from 183.9 ± 35.2mg/dl to 149.6 ± 29.0mg/dl (P=.007). In the group with walnut the HDL level rose from 41.7 ± 5.2mg/dl to 47.8 ± 5.4 mg/dl (P=.004) and the Castelli index (total cholesterol/HDL) decreased from 4.86 ± 0.97 to 3.82 ± 0.81 (P=.004). There were not significant changes in the CLA group. At the end of the essay, 46.7% of walnut group patients, 46.7% of n-3 group and 20% of CLA group, had no MS. The groups that consumed polyunsaturated fatty acids n-3 and those in walnut in moderate daily doses during 6 weeks had an improvement of the dyslipidemia component of MS, hypertriglyceridemia and low HDL level. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  19. Sialic acid mediated transcriptional modulation of a highly conserved sialometabolism gene cluster in Haemophilus influenzae and its effect on virulence

    Directory of Open Access Journals (Sweden)

    Moxon Richard

    2010-02-01

    Full Text Available Abstract Background Sialic acid has been shown to be a major virulence determinant in the pathogenesis of otitis media caused by the bacterium Haemophilus influenzae. This study aimed to characterise the expression of genes required for the metabolism of sialic acid and to investigate the role of these genes in virulence. Results Using qRT-PCR, we observed decreased transcriptional activity of genes within a cluster that are required for uptake and catabolism of 5-acetyl neuraminic acid (Neu5Ac, when bacteria were cultured in the presence of the sugar. We show that these uptake and catabolic genes, including a sialic acid regulatory gene (siaR, are highly conserved in the H. influenzae natural population. Mutant strains were constructed for seven of the nine genes and their influence upon LPS sialylation and resistance of the bacteria to the killing effect of normal human serum were assessed. Mutations in the Neu5Ac uptake (TRAP transporter genes decreased virulence in the chinchilla model of otitis media, but the attenuation was strain dependent. In contrast, mutations in catabolism genes and genes regulating sialic acid metabolism (siaR and crp did not attenuate virulence. Conclusion The commensal and pathogenic behaviour of H. influenzae involves LPS sialylation that can be influenced by a complex regulatory interplay of sialometabolism genes.

  20. mRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas

    Energy Technology Data Exchange (ETDEWEB)

    Castelli, Martina Galatea [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway); University of Bergen, Department of Biology, 5020 Bergen (Norway); Rusten, Marte; Goksøyr, Anders [University of Bergen, Department of Biology, 5020 Bergen (Norway); Routti, Heli, E-mail: heli.routti@npolar.no [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway)

    2014-01-15

    Highlights: •Genes regulating lipid metabolism were studied in ringed seals. •We compared highly contaminated Baltic seals and less contaminated Svalbard seals. •mRNA expression of hepatic PPARγ was higher in the Baltic seals. •mRNA expression of adipose PPARγ target genes was higher in the Baltic seals. •Contaminant exposure may affect lipid metabolism in the Baltic ringed seals. -- Abstract: There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes

  1. Enhanced d-lactic acid production by recombinant Saccharomyces cerevisiae following optimization of the global metabolic pathway.

    Science.gov (United States)

    Yamada, Ryosuke; Wakita, Kazuki; Mitsui, Ryosuke; Ogino, Hiroyasu

    2017-09-01

    Utilization of renewable feedstocks for the production of bio-based chemicals such as d-lactic acid by engineering metabolic pathways in the yeast Saccharomyces cerevisiae has recently become an attractive option. In this study, to realize efficient d-lactic acid production by S. cerevisiae, the expression of 12 glycolysis-related genes and the Leuconostoc mesenteroides d-LDH gene was optimized using a previously developed global metabolic engineering strategy, and repeated batch fermentation was carried out using the resultant strain YPH499/dPdA3-34/DLDH/1-18. Stable d-lactic acid production through 10 repeated batch fermentations was achieved using YPH499/dPdA3-34/DLDH/1-18. The average d-lactic acid production, productivity, and yield with 10 repeated batch fermentations were 60.3 g/L, 2.80 g/L/h, and 0.646, respectively. The present study is the first report of the application of a global metabolic engineering strategy for bio-based chemical production, and it shows the potential for efficient production of such chemicals by global metabolic engineering of the yeast S. cerevisiae. Biotechnol. Bioeng. 2017;114: 2075-2084. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals

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    Anastasia V. Shindyapina

    2017-12-01

    Full Text Available The healthy human body contains small amounts of metabolic formaldehyde (FA that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and in the gastrointestinal microbiome. With age, the ability to maintain a low level of FA decreases, which increases the risk of Alzheimer's disease and dementia. It has been shown that 1,2-dithiolane-3-pentanoic acid or alpha lipoic acid (ALA, a naturally occurring dithiol and antioxidant cofactor of mitochondrial α-ketoacid dehydrogenases, increases glutathione (GSH content and FA metabolism by mitochondrial aldehyde dehydrogenase 2 (ALDH2 thus manifests a therapeutic potential beyond its antioxidant property. We suggested that ALA can contribute to a decrease in the FA content of mammals by acting on ALDH2 expression. To test this assumption, we administered ALA in mice in order to examine the effect on FA metabolism and collected blood samples for the measurement of FA. Our data revealed that ALA efficiently eliminated FA in mice. Without affecting the specific activity of FA-metabolizing enzymes (ADH1, ALDH2, and ADH5, ALA increased the GSH content in the brain and up-regulated the expression of the FA-metabolizing ALDH2 gene in the brain, particularly in the hippocampus, but did not impact its expression in the liver in vivo or in rat liver isolated from the rest of the body. After ALA administration in mice and in accordance with the increased content of brain ALDH2 mRNA, we detected increased ALDH2 activity in brain homogenates. We hypothesized that the beneficial effects of ALA on patients with Alzheimer's disease may be associated with accelerated ALDH2-mediated FA detoxification and clearance.

  3. Fatty acid synthesis and pyruvate metabolism pathways remain active in dihydroartemisinin-induced dormant ring stages of Plasmodium falciparum.

    Science.gov (United States)

    Chen, Nanhua; LaCrue, Alexis N; Teuscher, Franka; Waters, Norman C; Gatton, Michelle L; Kyle, Dennis E; Cheng, Qin

    2014-08-01

    Artemisinin (ART)-based combination therapy (ACT) is used as the first-line treatment of uncomplicated falciparum malaria worldwide. However, despite high potency and rapid action, there is a high rate of recrudescence associated with ART monotherapy or ACT long before the recent emergence of ART resistance. ART-induced ring-stage dormancy and recovery have been implicated as possible causes of recrudescence; however, little is known about the characteristics of dormant parasites, including whether dormant parasites are metabolically active. We investigated the transcription of 12 genes encoding key enzymes in various metabolic pathways in P. falciparum during dihydroartemisinin (DHA)-induced dormancy and recovery. Transcription analysis showed an immediate downregulation for 10 genes following exposure to DHA but continued transcription of 2 genes encoding apicoplast and mitochondrial proteins. Transcription of several additional genes encoding apicoplast and mitochondrial proteins, particularly of genes encoding enzymes in pyruvate metabolism and fatty acid synthesis pathways, was also maintained. Additions of inhibitors for biotin acetyl-coenzyme A (CoA) carboxylase and enoyl-acyl carrier reductase of the fatty acid synthesis pathways delayed the recovery of dormant parasites by 6 and 4 days, respectively, following DHA treatment. Our results demonstrate that most metabolic pathways are downregulated in DHA-induced dormant parasites. In contrast, fatty acid and pyruvate metabolic pathways remain active. These findings highlight new targets to interrupt recovery of parasites from ART-induced dormancy and to reduce the rate of recrudescence following ART treatment. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. 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.

  5. Aberrant LPL Expression, Driven by STAT3, Mediates Free Fatty Acid Metabolism in CLL Cells.

    Science.gov (United States)

    Rozovski, Uri; Grgurevic, Srdana; Bueso-Ramos, Carlos; Harris, David M; Li, Ping; Liu, Zhiming; Wu, Ji Yuan; Jain, Preetesh; Wierda, William; Burger, Jan; O'Brien, Susan; Jain, Nitin; Ferrajoli, Alessandra; Keating, Michael J; Estrov, Zeev

    2015-05-01

    While reviewing chronic lymphocytic leukemia (CLL) bone marrow slides, we identified cytoplasmic lipid vacuoles in CLL cells but not in normal B cells. Because lipoprotein lipase (LPL), which catalyzes hydrolysis of triglycerides into free fatty acids (FFA), is aberrantly expressed in CLL, we investigated whether LPL regulates the oxidative metabolic capacity of CLL cells. We found that unlike normal B cells, CLL cells metabolize FFAs. Because STAT3 is constitutively activated in CLL cells and because we identified putative STAT3 binding sites in the LPL promoter, we sought to determine whether STAT3 drives the aberrant expression of LPL. Transfection of luciferase reporter gene constructs driven by LPL promoter fragments into MM1 cells revealed that STAT3 activates the LPL promoter. In addition, chromatin immunoprecipitation confirmed that STAT3 binds to the LPL promoter. Furthermore, transfection of CLL cells with STAT3-shRNA downregulated LPL transcripts and protein levels, confirming that STAT3 activates the LPL gene. Finally, transfection of CLL cells with LPL-siRNAs decreased the capacity of CLL cells to oxidize FFAs and reduced cell viability. Our study suggests that CLL cells adopt their metabolism to oxidize FFA. Activated STAT3 induces LPL, which catalyzes the hydrolysis of triglycerides into FFA. Therefore, inhibition of STAT3 is likely to prevent the capacity of CLL cells to utilize FFA. ©2015 American Association for Cancer Research.

  6. Mediterranean dietary pattern and VEGF +405 G/C gene polymorphisms in patients with metabolic syndrome: An aspect of gene-nutrient interaction.

    Science.gov (United States)

    Hajiluian, Ghazaleh; Abbasalizad Farhangi, Mahdieh; Jahangiry, Leila

    2017-01-01

    To evaluate the relationship between Mediterranean dietary pattern, anthropometric and metabolic biomarkers and vascular endothelial growth factor (VEGF) +405 G/C gene polymorphism in patient with metabolic syndrome (Mets). In this study 150 patients with Mets and 50 healthy subjects were enrolled. Dietary intakes were evaluated with a semi-quantitative food-frequency questionnaire (FFQ) and Mediterranean dietary quality index (Med-DQI) was assessed. Anthropometric assessments and blood pressure measurement were performed. Biochemical assays including fasting serum glucose (FSG), matrix metalloproteinase-3 (MMP-3), liver enzymes and lipid profiles were also assessed. Polymorphism of +405 G/C VEGF gene was determined utilizing polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method. Serum high density lipoprotein-cholesterol (HDL-C) was significantly lower and low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) concentrations and FSG were significantly higher in metabolic syndrome patients compared with control group (P Metabolic syndrome group with high consumption of "cholesterol" had significantly upper serum TG; also high consumption of "fish" and "vegetables-fruits" was associated with a significantly lower serum LDL concentrations. In metabolic syndrome patients with CC genotype, mean score of "saturated fatty acid" subgroup was significantly higher compared with other genotypes; whereas, in healthy individuals, mean score of "fruit-vegetable" subgroup in individuals of CC and GG genotype was significantly higher (Pmetabolic risk factors. We also indicated a higher "saturated fatty acid" intake in CC genotype among metabolic syndrome patients.

  7. Identifying genes and gene networks involved in chromium metabolism and detoxification in Crambe abyssinica

    Energy Technology Data Exchange (ETDEWEB)

    Zulfiqar, Asma, E-mail: asmazulfiqar08@yahoo.com [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States); Paulose, Bibin, E-mail: bpaulose@psis.umass.edu [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States); Chhikara, Sudesh, E-mail: sudesh@psis.umass.edu [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States); Dhankher, Om Parkash, E-mail: parkash@psis.umass.edu [Department of Plant, Soil, and Insect Sciences, 270 Stockbridge Road, University of Massachusetts Amherst, MA 01003 (United States)

    2011-10-15

    Chromium pollution is a serious environmental problem with few cost-effective remediation strategies available. Crambe abyssinica (a member of Brassicaseae), a non-food, fast growing high biomass crop, is an ideal candidate for phytoremediation of heavy metals contaminated soils. The present study used a PCR-Select Suppression Subtraction Hybridization approach in C. abyssinica to isolate differentially expressed genes in response to Cr exposure. A total of 72 differentially expressed subtracted cDNAs were sequenced and found to represent 43 genes. The subtracted cDNAs suggest that Cr stress significantly affects pathways related to stress/defense, ion transporters, sulfur assimilation, cell signaling, protein degradation, photosynthesis and cell metabolism. The regulation of these genes in response to Cr exposure was further confirmed by semi-quantitative RT-PCR. Characterization of these differentially expressed genes may enable the engineering of non-food, high-biomass plants, including C. abyssinica, for phytoremediation of Cr-contaminated soils and sediments. - Highlights: > Molecular mechanism of Cr uptake and detoxification in plants is not well known. > We identified differentially regulated genes upon Cr exposure in Crambe abyssinica. > 72 Cr-induced subtracted cDNAs were sequenced and found to represent 43 genes. > Pathways linked to stress, ion transport, and sulfur assimilation were affected. > This is the first Cr transcriptome study in a crop with phytoremediation potential. - This study describes the identification and isolation of differentially expressed genes involved in chromium metabolism and detoxification in a non-food industrial oil crop Crambe abyssinica.

  8. PROTEIN METABOLISM IN REGENERATING WOUND TISSUE: FUNCTION OF THE SULFUR AMINO ACIDS.

    Science.gov (United States)

    PROTEINS, *TISSUES(BIOLOGY), METABOLISM, TISSUES(BIOLOGY), REGENERATION(ENGINEERING), WOUNDS AND INJURIES, TISSUES(BIOLOGY), TRACER STUDIES, METHIONINE, COLLAGEN, TYROSINE, BIOSYNTHESIS, AMINO ACIDS .

  9. Maternal smoking, xenobiotic metabolizing enzyme gene variants, and gastroschisis risk.

    Science.gov (United States)

    Jenkins, Mary M; Reefhuis, Jennita; Gallagher, Margaret L; Mulle, Jennifer G; Hoffmann, Thomas J; Koontz, Deborah A; Sturchio, Cynthia; Rasmussen, Sonja A; Witte, John S; Richter, Patricia; Honein, Margaret A

    2014-06-01

    Maternal smoking during pregnancy is one proposed risk factor for gastroschisis, but reported associations have been modest, suggesting that differences in genetic susceptibility might play a role. We included 108 non-Hispanic white and 62 Hispanic families who had infants with gastroschisis, and 1,147 non-Hispanic white and 337 Hispanic families who had liveborn infants with no major structural birth defects (controls) in these analyses. DNA was extracted from buccal cells collected from infants and mothers, and information on periconceptional smoking history was obtained from maternal interviews, as part of the National Birth Defects Prevention Study. We analyzed five polymorphisms in three genes that code for enzymes involved in metabolism of some cigarette smoke constituents (CYP1A1, CYP1A2, and NAT2). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) independently for maternal smoking and maternal and infant gene variants, and to assess joint associations of maternal smoking and maternal or infant gene variants with gastroschisis. In analyses adjusted for maternal age at delivery and stratified by maternal race-ethnicity, we identified three suggestive associations among 30 potential associations with sufficient numbers to calculate ORs: CYP1A1*2A for non-Hispanic white mothers who smoked periconceptionally (aOR = 0.38, 95% CI 0.15-0.98), and NAT2*6 for Hispanic non-smoking mothers (aOR = 2.17, 95% CI 1.12-4.19) and their infants (aOR = 2.11, 95% CI 1.00-4.48). This analysis does not support the occurrence of effect modification between periconceptional maternal smoking and most of the xenobiotic metabolizing enzyme gene variants assessed. © 2014 Wiley Periodicals, Inc.

  10. Genome-wide identification of Saccharomyces cerevisiae genes required for tolerance to acetic acid

    Science.gov (United States)

    2010-01-01

    Background Acetic acid is a byproduct of Saccharomyces cerevisiae alcoholic fermentation. Together with high concentrations of ethanol and other toxic metabolites, acetic acid may contribute to fermentation arrest and reduced ethanol productivity. This weak acid is also a present in lignocellulosic hydrolysates, a highly interesting non-feedstock substrate in industrial biotechnology. Therefore, the better understanding of the molecular mechanisms underlying S. cerevisiae tolerance to acetic acid is essential for the rational selection of optimal fermentation conditions and the engineering of more robust industrial strains to be used in processes in which yeast is explored as cell factory. Results The yeast genes conferring protection against acetic acid were identified in this study at a genome-wide scale, based on the screening of the EUROSCARF haploid mutant collection for susceptibility phenotypes to this weak acid (concentrations in the range 70-110 mM, at pH 4.5). Approximately 650 determinants of tolerance to acetic acid were identified. Clustering of these acetic acid-resistance genes based on their biological function indicated an enrichment of genes involved in transcription, internal pH homeostasis, carbohydrate metabolism, cell wall assembly, biogenesis of mitochondria, ribosome and vacuole, and in the sensing, signalling and uptake of various nutrients in particular iron, potassium, glucose and amino acids. A correlation between increased resistance to acetic acid and the level of potassium in the growth medium was found. The activation of the Snf1p signalling pathway, involved in yeast response to glucose starvation, is demonstrated to occur in response to acetic acid stress but no evidence was obtained supporting the acetic acid-induced inhibition of glucose uptake. Conclusions Approximately 490 of the 650 determinants of tolerance to acetic acid identified in this work are implicated, for the first time, in tolerance to this weak acid. These are

  11. Genome-wide identification of Saccharomyces cerevisiae genes required for tolerance to acetic acid

    Directory of Open Access Journals (Sweden)

    Sá-Correia Isabel

    2010-10-01

    Full Text Available Abstract Background Acetic acid is a byproduct of Saccharomyces cerevisiae alcoholic fermentation. Together with high concentrations of ethanol and other toxic metabolites, acetic acid may contribute to fermentation arrest and reduced ethanol productivity. This weak acid is also a present in lignocellulosic hydrolysates, a highly interesting non-feedstock substrate in industrial biotechnology. Therefore, the better understanding of the molecular mechanisms underlying S. cerevisiae tolerance to acetic acid is essential for the rational selection of optimal fermentation conditions and the engineering of more robust industrial strains to be used in processes in which yeast is explored as cell factory. Results The yeast genes conferring protection against acetic acid were identified in this study at a genome-wide scale, based on the screening of the EUROSCARF haploid mutant collection for susceptibility phenotypes to this weak acid (concentrations in the range 70-110 mM, at pH 4.5. Approximately 650 determinants of tolerance to acetic acid were identified. Clustering of these acetic acid-resistance genes based on their biological function indicated an enrichment of genes involved in transcription, internal pH homeostasis, carbohydrate metabolism, cell wall assembly, biogenesis of mitochondria, ribosome and vacuole, and in the sensing, signalling and uptake of various nutrients in particular iron, potassium, glucose and amino acids. A correlation between increased resistance to acetic acid and the level of potassium in the growth medium was found. The activation of the Snf1p signalling pathway, involved in yeast response to glucose starvation, is demonstrated to occur in response to acetic acid stress but no evidence was obtained supporting the acetic acid-induced inhibition of glucose uptake. Conclusions Approximately 490 of the 650 determinants of tolerance to acetic acid identified in this work are implicated, for the first time, in tolerance to

  12. The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Frederiksen, Hans-Jørgen

    2012-01-01

    Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA...

  13. Uric acid metabolism in patients with primary gout and the metabolic syndrome.

    Science.gov (United States)

    Fraile, J M; Puig, J G; Torres, Rosa J; de Miguel, Eugenio; Martínez, Pedro; Vázquez, J J

    2010-06-01

    Forty-four patients (40 males) with a mean age of 58 years were included in this pilot study. Mean serum urate concentration in patients with and without the metabolic syndrome (MS) was 8.8 mg/dL and 8.1 mg/dL, respectively. Urinary uric acid excretion was 543 mg/day/1.73 m(2) in the former and 609 mg/day/1.73 m(2) in the latter. Uric acid to creatinine ratio was 0.37 mg/mg in patients with the MS and 0.42 mg/mg in those without the MS. Mean serum urate increased from 8.6 mg/dL in subjects with three or more MS components to 10.3 mg/dL in those with five MS components. Serum urate was markedly lower in patients with mild MS (9 patients, 8.6 mg/dL) as compared to severe MS (10 patients, 9.2 mg/dL). In contrast, urinary uric acid to creatinine ratio was 0.42 mg/mg in patients with gout and mild MS and 0.33 mg/mg in gout patients with severe MS. Uric acid underexcretion appears to be more severe in gout patients with the MS. This disturbance appears to be related to the severity of the MS.

  14. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  15. Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

    2017-11-01

    Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered (Pcitric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

  16. Ascorbic acid metabolism during bilberry (Vaccinium myrtillus L.) fruit development.

    Science.gov (United States)

    Cocetta, Giacomo; Karppinen, Katja; Suokas, Marko; Hohtola, Anja; Häggman, Hely; Spinardi, Anna; Mignani, Ilaria; Jaakola, Laura

    2012-07-15

    Bilberry (Vaccinium myrtillus L.) possesses a high antioxidant capacity in berries due to the presence of anthocyanins and ascorbic acid (AsA). Accumulation of AsA and the expression of the genes encoding the enzymes of the main AsA biosynthetic route and of the ascorbate-glutathione cycle, as well as the activities of the enzymes involved in AsA oxidation and recycling were investigated for the first time during the development and ripening of bilberry fruit. The results showed that the AsA level remained relatively stable during fruit maturation. The expression of the genes encoding the key enzymes in the AsA main biosynthetic route showed consistent trends with each other as well as with AsA levels, especially during the first stages of fruit ripening. The expression of genes and activities of the enzyme involved in the AsA oxidation and recycling route showed more prominent developmental stage-dependent changes during the ripening process. Different patterns of activity were found among the studied enzymes and the results were, for some enzymes, in accordance with AsA levels. In fully ripe berries, both AsA content and gene expression were significantly higher in skin than in pulp. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Modulating gene function with peptide nucleic acids (PNA)

    DEFF Research Database (Denmark)

    Nielsen, Peter E.; Crooke, Stanley T.

    2008-01-01

    A review on peptide nucleic acid (PNA) oligomers as modulators of gene expression ranging from gene silencing at the mRNAor the dsDNA (antigene) level, and redirection of mRNA splicing to gene activation through transcription bubble mimicking. PNA chem., anti-infective agents, cellular delivery, ......, and in vivo bioavailability of PNA are briefly discussed. [on SciFinder (R)]...

  18. Megaloblastic anaemia: Folic acid and vitamin B12 metabolism

    Directory of Open Access Journals (Sweden)

    H.B. Castellanos-Sinco

    2015-07-01

    Full Text Available Folic acid and cobalamin are B-group vitamins that play an essential role in many cellular processes. Deficiency in one or both of these vitamins causes megaloblastic anaemia, a disease characterized by the presence of megaloblasts. Megaloblasts occur when inhibition of DNA synthesis causes asynchronous maturation between the nucleus and the cytoplasm. Clinical manifestations are similar to those of other types of anaemia, with the exception of cobalamin deficiency megaloblastic anaemia, which presents distinctive neurological symptoms. An understanding of the metabolism of these vitamins will enable clinicians to make the best use and interpretation of laboratory studies and monitor therapeutic strategies, which consist mainly of administering supplements to restore body reserves.

  19. Specific plasma amino acid disturbances associated with metabolic syndrome.

    Science.gov (United States)

    Siomkajło, Marta; Rybka, Jacek; Mierzchała-Pasierb, Magdalena; Gamian, Andrzej; Stankiewicz-Olczyk, Joanna; Bolanowski, Marek; Daroszewski, Jacek

    2017-12-01

    The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process. Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(-): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed. The ability of the BCAA and AAA to discriminate subjects with MS and insulin resistance was tested. Based on logistic discrimination, a multivariate early MS diagnostic model was built, and its discrimination properties were evaluated. Two functionally independent amino acid clusters were identified. BCAA and phenylalanine differed significantly between MS(+) and MS(-) participants (P = 0.003). These factors were also found to be indicators of MS(+) individuals (AUC: 0.66; 95% CI: 0.5757-0.7469), and correlated with cardiometabolic factors. No statistically significant differences in amino acid concentrations between those with and without insulin resistance were noted, and none of the amino groups were indicators of insulin resistance. The proposed MS multivariate diagnostic model consisted of phenylalanine, insulin, leptin, and adiponectin, and had good discrimination properties [AUC 0.79; 95% CI: 0.7239-0.8646]. MS is associated with selective BCAA and AAA profile disturbances, which could be part of cardiometabolic disease pathogenesis and derive neither directly from insulin sensitivity impairment, nor obesity or muscle mass. The MS diagnostic model developed and described herein should be validated in future studies.

  20. Protein and amino acid metabolism in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guoyao.

    1989-01-01

    Isolated chick extensor digitorum communis (EDC) muscles and, in some experiments, rat skeletal muscles were used to study a number of aspects of protein and amino acid metabolism. (1) Chick EDC muscles synthesize and release large amounts of alanine and glutamine, which indirectly obtain their amino groups from branched-chain amino acids (BCAA). (2) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) decrease (P < 0.01) alanine synthesis and BCAA transamination in EDC muscles from 24-h fasted chicks by decreasing (P < 0.01) intracellular concentrations of pyruvate due to inhibition of glycolysis. (3) Glutamine is extensively degraded in skeletal muscles from both chicks and rats, thus challenging the traditional view that glutamine oxidation is negligible in skeletal muscle. The cytosolic glutamine aminotransferases L and K in the rat and the mitochondrial phosphate-activated glutaminase in the chick play important roles in the conversion of glutamine to {alpha}-ketoglutarate for further oxidation. (4) Although methionine has been reported to be extensively transaminated in rat skeletal muscle preparations in the absence of other amino acids, transamination of methionine is absent or negligible in chick and rat skeletal muscles in the presence of physiological concentrations of amino acids. (5) Glutamine at 1.0-15 mM increases (P < 0.01) protein synthesis ({sup 3}H-phenylalanine incorporation), and at 10.0-15.0 mM decreases (P < 0.05) protein degradation ({sup 3}H-phenylalanine release from prelabelled protein in vivo) in EDC muscles from fed chicks as compared to muscles incubated in the absence of glutamine. (6) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) has a small but significant inhibitory effect (P < 0.05) on the rate of protein synthesis, but has no effect (P > 0.05) on the rate of protein degradation in EDC muscles from fed chicks.

  1. Vitamin D metabolic pathway genes and pancreatic cancer risk.

    Directory of Open Access Journals (Sweden)

    Hannah Arem

    Full Text Available Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN totaling 213 single nucleotide polymorphisms (SNPs, and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L for the most significant SNPs using a subset of cohort cases (n = 713 and controls (n = 878. The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830. Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186, LRP2 (rs4668123, CYP24A1 (rs2762932, GC (rs2282679, and CUBN (rs1810205 genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037, but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

  2. Metabolic capabilities of Actinobacillus succinogenes for succinic acid production

    Directory of Open Access Journals (Sweden)

    R. Rafieenia

    2014-12-01

    Full Text Available Attention has been focused on microbial succinic acid production as an alternative for conventional chemical synthesis that is associated with environmental pollution. A metabolic model for Actinobacillus succinogenes 130Z was developed with a mixture of glucose and xylose as substrate. The metabolic fluxes during succinicate production were determined using flux balance analysis by linear programming optimization in the MATLAB environment. Different glucose ratios (0.3, 0.4 and 0.7 mol.mol-1substrate were used as model assumptions to calculate optimal fluxes, maximum growth and succinate production. The model revealed that higher growth rates and product yields were correlated with higher glucose content in the substrate mixture. When glucose constituted 0.5 mol.mol-1 substrate, a lower succinate yield (0.64 mol.mol-1 substrate was obtained, compared to 0.73 mol.mol-1 substrate when glucose was used individually. Deletion of different unessential reactions in the model showed that a knockout of the acetate formation pathway would increase the succinate yield by 21% when glucose and xylose were used in equal molar ratios.

  3. Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

    Science.gov (United States)

    Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andrés Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

    2012-01-01

    Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

  4. Acyl-CoA N-acyltransferase influences fertility by regulating lipid metabolism and jasmonic acid biogenesis in cotton.

    Science.gov (United States)

    Fu, Wenfeng; Shen, Ying; Hao, Juan; Wu, Jianyong; Ke, Liping; Wu, Caiyun; Huang, Kai; Luo, Binglun; Xu, Mingfeng; Cheng, Xiaofei; Zhou, Xueping; Sun, Jie; Xing, Chaozhu; Sun, Yuqiang

    2015-07-02

    Cotton (Gossypium spp.) is an important economic crop and there is obvious heterosis in cotton, fertility has played an important role in this heterosis. However, the genes that exhibit critical roles in anther development and fertility are not well understood. Here, we report an acyl-CoA N-acyltransferase (EC2.3; GhACNAT) that plays a key role in anther development and fertility. Suppression of GhACNAT by virus-induced gene silencing in transgenic cotton (G. hirsutum L. cv. C312) resulted in indehiscent anthers that were full of pollen, diminished filaments and stamens, and plant sterility. We found GhACNAT was involved in lipid metabolism and jasmonic acid (JA) biosynthesis. The genes differentially expressed in GhACNAT-silenced plants and C312 were mainly involved in catalytic activity and transcription regulator activity in lipid metabolism. In GhACNAT-silenced plants, the expression levels of genes involved in lipid metabolism and jasmonic acid biosynthesis were significantly changed, the amount of JA in leaves and reproductive organs was significantly decreased compared with the amounts in C312. Treatments with exogenous methyl jasmonate rescued anther dehiscence and pollen release in GhACNAT-silenced plants and caused self-fertility. The GhACNAT gene may play an important role in controlling cotton fertility by regulating the pathways of lipid synthesis and JA biogenesis.

  5. Identification of circular RNAs from the parental genes involved in multiple aspects of cellular metabolism in barley

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Noeparvar, Shahin; Borg, Søren

    2016-01-01

    RNA circularization made by head-to-tail back-splicing events is involved in the regulation of gene expression from transcriptional to post-translational levels. By exploiting RNA-Seq data and down-stream analysis, we shed light on the importance of circular RNAs in plants. The results introduce...... circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular...... protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes...

  6. Exercise, sex, menstrual cycle phase, and 17beta-estradiol influence metabolism-related genes in human skeletal muscle.

    Science.gov (United States)

    Fu, Ming-hua H; Maher, Amy C; Hamadeh, Mazen J; Ye, Changhua; Tarnopolsky, Mark A

    2009-12-30

    Higher fat and lower carbohydrate and amino acid oxidation are observed in women compared with men during endurance exercise. We hypothesized that the observed sex difference is due to estrogen and that menstrual cycle phase or supplementation of men with 17beta-estradiol (E(2)) would coordinately influence the mRNA content of genes involved in lipid and/or carbohydrate metabolism in skeletal muscle. Twelve men and twelve women had muscle biopsies taken before and immediately after 90 min of cycling at 65% peak oxygen consumption (Vo(2peak)). Women were studied in the midfollicular (Fol) and midluteal (Lut) phases, and men were studied after 8 days of E(2) or placebo supplementation. Targeted RT-PCR was used to compare mRNA content for genes involved in transcriptional regulation and lipid, carbohydrate, and amino acid metabolism. Sex was the greatest predictor of substrate metabolism gene content. Sex affected the mRNA content of FATm, FABPc, SREBP-1c, mtGPAT, PPARdelta, PPARalpha, CPTI, TFP-alpha, GLUT4, HKII, PFK, and BCOADK (P Menstrual cycle had a small effect on PPARdelta, GP, and glycogenin mRNA content. Overall, women have greater mRNA content for several genes involved in lipid metabolism, which is partially due to an effect of E(2).

  7. Production of L-lactic acid from metabolically engineered strain of Enterobacter aerogenes ATCC 29007.

    Science.gov (United States)

    Thapa, Laxmi Prasad; Lee, Sang Jun; Park, Chulhwan; Kim, Seung Wook

    2017-07-01

    In this study, L-lactic acid production was investigated from metabolically engineered strain of E. aerogenes ATCC 29007. The engineered strain E. aerogenes SUMI01 (Δpta) was generated by the deletion of phosphate acetyltransferase (pta) gene from the chromosome of E. aerogenes ATCC 29007 and deletion was confirmed by colony PCR. Under the optimized fermentation conditions, at 37°C and pH 6 for 84h, the L-lactic acid produced by engineered strain E. aerogenes SUMI01 (Δpta) in flask fermentation using 100g/L mannitol as the carbon source was 40.05g/L as compared to that of the wild type counterpart 20.70g/L. At the end of the batch fermentation in bioreactor the production of L-lactic acid reached to 46.02g/L and yield was 0.41g/g by utilizing 112.32g/L mannitol. This is the first report regarding the production of L-lactic acid from Enterobacter species. We believe that this result may provide valuable guidelines for further engineering Enterobacter strain for the improvement of L-lactic acid production. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The effects of prenatal metformin on obesogenic diet-induced alterations in maternal and fetal fatty acid metabolism.

    Science.gov (United States)

    Harris, Kemoy; Desai, Neeraj; Gupta, Madhu; Xue, Xiangying; Chatterjee, Prodyot K; Rochelson, Burton; Metz, Christine N

    2016-01-01

    Maternal obesity may program the fetus and increase the susceptibility of the offspring to adult diseases. Metformin crosses the placenta and has been associated with decreased inflammation and reversal of fatty liver in obese leptin-deficient mice. We investigated the effects of metformin on maternal and fetal lipid metabolism and hepatic inflammation using a rat model of diet-induced obesity during pregnancy. Female Wistar rats (6-7 weeks old) were fed normal or high calorie diets for 5 weeks. After mating with normal-diet fed males, half of the high calorie-fed dams received metformin (300 mg/kg, daily); dams (8 per group) continued diets through gestational day 19. Maternal and fetal livers and fetal brains were analyzed for fatty acids and for fatty acid metabolism-related gene expression. Data were analyzed by ANOVA followed by Dunnett's post hoc testing. When compared to control-lean maternal livers, obesogenic-diet-exposed maternal livers showed significantly higher saturated fatty acids (14:0 and 16:0) and monounsaturated fatty acids (16:1n7 and 18:1n9) and lower polyunsaturated (18:2n6 and 20:4n6 [arachidonic acid]) and anti-inflammatory n3 polyunsaturated fatty acids (18:3n3 and 22:6n3 [docosahexaenoic acid]) (p obesogenic diet exposure significantly increased fetal liver IFNγ levels (p < 0.05), which was reversed by maternal metformin treatment (p < 0.05). Consumption of a high calorie diet significantly affected maternal and fetal fatty acid metabolism. It reduced anti-inflammatory polyunsaturated fatty acids in maternal and fetal livers, altered gene expression of fatty acid metabolism markers, and induced inflammation in the fetal livers. Prenatal metformin attenuated some diet-induced fatty acid changes and inflammation in the fetal livers without affecting maternal livers, suggesting that maternal metformin may impact fetal/neonatal fatty acid/lipid metabolism.

  9. Uric acid in metabolic syndrome: From an innocent bystander to a central player.

    Science.gov (United States)

    Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A; Nakagawa, Takahiko; Johnson, Richard J

    2016-04-01

    Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. Copyright © 2015 European Federation of Internal Medicine. All rights reserved.

  10. Uric acid in metabolic syndrome: From an innocent bystander to a central player

    Science.gov (United States)

    Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.

    2016-01-01

    Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429

  11. Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism

    Science.gov (United States)

    Duparc, Thibaut; Plovier, Hubert; Marrachelli, Vannina G; Van Hul, Matthias; Essaghir, Ahmed; Ståhlman, Marcus; Matamoros, Sébastien; Geurts, Lucie; Pardo-Tendero, Mercedes M; Druart, Céline; Delzenne, Nathalie M; Demoulin, Jean-Baptiste; van der Merwe, Schalk W; van Pelt, Jos; Bäckhed, Fredrik; Monleon, Daniel; Everard, Amandine; Cani, Patrice D

    2017-01-01

    Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. Design To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). Results Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Conclusions Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans. PMID

  12. Hepatotoxicity prediction by systems biology modeling of disturbed metabolic pathways using gene expression data.

    Science.gov (United States)

    Carbonell, Pablo; Lopez, Oriol; Amberg, Alexander; Pastor, Manuel; Sanz, Ferran

    2017-01-01

    The present study applies a systems biology approach for the in silico predictive modeling of drug toxicity on the basis of high-quality preclinical drug toxicity data with the aim of increasing the mechanistic understanding of toxic effects of compounds at different levels (pathway, cell, tissue, organ). The model development was carried out using 77 compounds for which gene expression data for treated primary human hepatocytes is available in the LINCS database and for which rodent in vivo hepatotoxicity information is available in the eTOX database. The data from LINCS were used to determine the type and number of pathways disturbed by each compound and to estimate the extent of disturbance (network perturbation elasticity), and were used to analyze the correspondence with the in vivo information from eTOX. Predictive models were developed through this integrative analysis, and their specificity and sensitivity were assessed. The quality of the predictions was determined on the basis of the area under the curve (AUC) of plots of true positive vs. false positive rates (ROC curves). The ROC AUC reached values of up to 0.9 (out of 1.0) for some hepatotoxicity endpoints. Moreover, the most frequently disturbed metabolic pathways were determined across the studied toxicants. They included, e.g., mitochondrial beta-oxidation of fatty acids and amino acid metabolism. The process was exemplified by successful predictions on various statins. In conclusion, an entirely new approach linking gene expression alterations to the prediction of complex organ toxicity was developed and evaluated.

  13. Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring.

    Science.gov (United States)

    Mennitti, Laís V; Oliveira, Juliana L; Morais, Carina A; Estadella, Débora; Oyama, Lila M; Oller do Nascimento, Claudia M; Pisani, Luciana P

    2015-02-01

    During pregnancy and/or lactation, maternal nutrition is related to the adequate development of the fetus, newborn and future adult, likely by modifications in fetal programming and epigenetic regulation. Fetal programming is characterized by adaptive responses to specific environmental conditions during early life stages, which may alter gene expression and permanently affect the structure and function of several organs and tissues, thus influencing the susceptibility to metabolic disorders. Regarding lipid metabolism during the first two trimesters of pregnancy, the maternal body accumulates fat, whereas in late pregnancy, the lipolytic activity in the maternal adipose tissue is increased. However, an excess or deficiency of certain fatty acids may lead to adverse consequences to the fetuses and newborns. Fetal exposure to trans fatty acids appears to promote early deleterious effects in the offspring's health, thereby increasing the individual risk for developing metabolic diseases throughout life. Similarly, the maternal intake of saturated fatty acids seems to trigger alterations in the liver and adipose tissue function associated with insulin resistance and diabetes. The polyunsaturated fatty acids (PUFAs), particularly long-chain PUFAs (long-chain PUFA-arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid), play an important and beneficial physiologic role in the offspring who receive this fatty acid during critical periods of development. Therefore, the maternal nutritional condition and fatty acid intake during pregnancy and/or lactation are critical factors that are strongly associated with normal fetal and postnatal development, which influence the modifications in fetal programming and in the individual risk for developing metabolic diseases throughout life. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Transcriptome and metabolome analyses of sugar and organic acid metabolism in Ponkan (Citrus reticulata) fruit during fruit maturation.

    Science.gov (United States)

    Lin, Qiong; Wang, Chengyang; Dong, Wencheng; Jiang, Qing; Wang, Dengliang; Li, Shaojia; Chen, Ming; Liu, Chunrong; Sun, Chongde; Chen, Kunsong

    2015-01-01

    Ponkan (Citrus reticulata Blanco cv. Ponkan) is an important mandarin citrus in China. However, the low ratio of sugars to organic acids makes it less acceptable for consumers. In this work, three stages (S120, early development stage; S195, commercial harvest stage; S205, delayed harvest stage) of Ponkan fruit were selected for study. Among 28 primary metabolites analyzed in fruit, sugars increased while organic acids in general decreased. RNA-Seq analysis was carried out and 19,504 genes were matched to the Citrus clementina genome, with 85 up-regulated and 59 down-regulated genes identified during fruit maturation. A sucrose phosphate synthase (SPS) gene was included in the up-regulated group, and this was supported by the transcript ratio distribution. Expression of two asparagine transferases (AST), and a specific ATP-citrate lyase (ACL) and glutamate decarboxylase (GAD) members increased during fruit maturation. It is suggested that SPS, AST, ACL and GAD coordinately contribute to sugar accumulation and organic acid degradation during Ponkan fruit maturation. Both the glycolysis pathway and TCA cycle were accelerated during later maturation, indicating the flux change from sucrose metabolism to organic acid metabolism was enhanced, with citrate degradation occurring mainly through the gamma-aminobutyric acid (GABA) and acetyl-CoA pathways. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants.

    Science.gov (United States)

    Schläpfer, Pascal; Zhang, Peifen; Wang, Chuan; Kim, Taehyong; Banf, Michael; Chae, Lee; Dreher, Kate; Chavali, Arvind K; Nilo-Poyanco, Ricardo; Bernard, Thomas; Kahn, Daniel; Rhee, Seung Y

    2017-04-01

    Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters. © 2017 American Society of Plant Biologists. All Rights Reserved.

  16. Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants1[OPEN

    Science.gov (United States)

    Zhang, Peifen; Kim, Taehyong; Banf, Michael; Chavali, Arvind K.; Nilo-Poyanco, Ricardo; Bernard, Thomas

    2017-01-01

    Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters. PMID:28228535

  17. Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans

    Science.gov (United States)

    2013-01-01

    Background Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics. Results We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes. Conclusions This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases. PMID:23496871

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

    Science.gov (United States)

    Fonknechten, Nuria; Chaussonnerie, Sébastien; Tricot, Sabine; Lajus, Aurélie; Andreesen, Jan R; Perchat, Nadia; Pelletier, Eric; Gouyvenoux, Michel; Barbe, Valérie; Salanoubat, Marcel; Le Paslier, Denis; Weissenbach, Jean; Cohen, Georges N; Kreimeyer, Annett

    2010-10-11

    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. 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. Analysis of the C. sticklandii genome and additional experimental procedures

  20. Vitamin D metabolic pathway genes and pancreatic cancer risk.

    Science.gov (United States)

    Arem, Hannah; Yu, Kai; Xiong, Xiaoqin; Moy, Kristin; Freedman, Neal D; Mayne, Susan T; Albanes, Demetrius; Arslan, Alan A; Austin, Melissa; Bamlet, William R; Beane-Freeman, Laura; Bracci, Paige; Canzian, Federico; Cotterchio, Michelle; Duell, Eric J; Gallinger, Steve; Giles, Graham G; Goggins, Michael; Goodman, Phyllis J; Hartge, Patricia; Hassan, Manal; Helzlsouer, Kathy; Henderson, Brian; Holly, Elizabeth A; Hoover, Robert; Jacobs, Eric J; Kamineni, Aruna; Klein, Alison; Klein, Eric; Kolonel, Laurence N; Li, Donghui; Malats, Núria; Männistö, Satu; McCullough, Marjorie L; Olson, Sara H; Orlow, Irene; Peters, Ulrike; Petersen, Gloria M; Porta, Miquel; Severi, Gianluca; Shu, Xiao-Ou; Visvanathan, Kala; White, Emily; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Tobias, Geoffrey S; Maeder, Dennis; Brotzman, Michelle; Risch, Harvey; Sampson, Joshua N; Stolzenberg-Solomon, Rachael Z

    2015-01-01

    Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of pcancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

  1. The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

    Directory of Open Access Journals (Sweden)

    Rudock Megan E

    2011-05-01

    Full Text Available Abstract Background Arachidonic acid (AA is a long-chain omega-6 polyunsaturated fatty acid (PUFA synthesized from the precursor dihomo-gamma-linolenic acid (DGLA that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. Results In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10-48 and lower DGLA levels (p = 9.80 × 10-11 than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs in the Fatty Acid Desaturase (FADS locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans. Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537, wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. Conclusions We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

  2. The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans.

    Science.gov (United States)

    Mathias, Rasika A; Sergeant, Susan; Ruczinski, Ingo; Torgerson, Dara G; Hugenschmidt, Christina E; Kubala, Meghan; Vaidya, Dhananjay; Suktitipat, Bhoom; Ziegler, Julie T; Ivester, Priscilla; Case, Douglas; Yanek, Lisa R; Freedman, Barry I; Rudock, Megan E; Barnes, Kathleen C; Langefeld, Carl D; Becker, Lewis C; Bowden, Donald W; Becker, Diane M; Chilton, Floyd H

    2011-05-20

    Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10(-48)) and lower DGLA levels (p = 9.80 × 10(-11)) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10(-16) in African Americans, 2.68 × 10(-23) in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

  3. Expressing yeast SAMdc gene confers broad changes in gene expression and alters fatty acid composition in tomato fruit.

    Science.gov (United States)

    Kolotilin, Igor; Koltai, Hinanit; Bar-Or, Carmiya; Chen, Lea; Nahon, Sahadia; Shlomo, Haviva; Levin, Ilan; Reuveni, Moshe

    2011-07-01

    Tomato (Solanum lycopersicum) fruits expressing a yeast S-adenosyl methionine decarboxylase (ySAMdc) gene under control of a ripening-induced promoter show altered phytonutrient content and broad changes in gene expression. Genome-wide transcriptional alterations in pericarp tissues of the ySAMdc-expressing fruits are shown. Consistent with the ySAMdc expression pattern from the ripening-induced promoter, very minor transcriptional alterations were detected at the mature green developmental stage. At the breaker and red stages, altered levels of numerous transcripts were observed with a general tendency toward upregulation in the transgenic fruits. Ontological analysis of up- and downregulated transcript groups revealed various affected metabolic processes, mainly carbohydrate and amino acid metabolism, and protein synthesis, which appeared to be intensified in the ripening transgenic fruits. Other functional ontological categories of altered transcripts represented signal transduction, transcription regulation, RNA processing, molecular transport and stress response, as well as metabolism of lipids, glycans, xenobiotics, energy, cofactors and vitamins. In addition, transcript levels of genes encoding structural enzymes for several biosynthetic pathways showed strong correlations to levels of specific metabolites that displayed altered levels in transgenic fruits. Increased transcript levels of fatty acid biosynthesis enzymes were accompanied by a change in the fatty acid profile of transgenic fruits, most notably increasing ω-3 fatty acids at the expense of other lipids. Thus, SAMdc is a prime target in manipulating the nutritional value of tomato fruits. Combined with analyses of selected metabolites in the overripe fruits, a model of enhanced homeostasis of the pericarp tissue in the polyamine-accumulating tomatoes is proposed. Copyright © Physiologia Plantarum 2011.

  4. Metabolic regulation of the plant hormone indole-3-acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Jerry D. Cohen

    2009-11-01

    The phytohormone indole-3-acetic acid (IAA, auxin) is important for many aspects of plant growth, development and responses to the environment yet the routes to is biosynthesis and mechanisms for regulation of IAA levels remain important research questions. A critical issue concerning the biosynthesis if IAA in plants is that redundant pathways for IAA biosynthesis exist in plants. We showed that these redundant pathways and their relative contribution to net IAA production are under both developmental and environmental control. We worked on three fundamental problems related to how plants get their IAA: 1) An in vitro biochemical approach was used to define the tryptophan dependent pathway to IAA using maize endosperm, where relatively large amounts of IAA are produced over a short developmental period. Both a stable isotope dilution and a protein MS approach were used to identify intermediates and enzymes in the reactions. 2) We developed an in vitro system for analysis of tryptophan-independent IAA biosynthesis in maize seedlings and we used a metabolite profiling approach to isolate intermediates in this reaction. 3) Arabidopsis contains a small family of genes that encode potential indolepyruvate decarboxylase enzymes. We cloned these genes and studied plants that are mutant in these genes and that over-express each member in the family in terms of the level and route of IAA biosynthesis. Together, these allowed further development of a comprehensive picture of the pathways and regulatory components that are involved in IAA homeostasis in higher plants.

  5. Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults.

    Science.gov (United States)

    Zhang, Mei-Lin; Gao, Yu-Xia; Wang, Xuan; Chang, Hong; Huang, Guo-Wei

    2013-01-01

    The relation between serum uric acid and metabolic syndrome is observed not only with frank hyperuricemia but also with serum uric acid levels within the normal range. The current "normal" range set for hyperuricemia often fails to identify patients with potential metabolic disorders. We investigate the association between serum uric acid within the normal range and incident metabolic syndrome risk, and further to determine the optimal cut-off value of serum uric acid for the diagnosis or prediction of metabolic syndrome. A total of 7399 Chinese adults (2957 men and 4442 women; ≥20 years) free of metabolic syndrome were followed for 3 years. During the 3-year follow-up, 1190 normouricemic individuals developed metabolic syndrome (16.1%). After adjusting the associated variables, the top quartile of serum uric acid levels was associated with higher metabolic syndrome development compared with the bottom quartile in men (hazard ratio (HR), 1.29; puric acid to identify metabolic syndrome were 6.3 mg/dl in men and 4.9 mg/dl in women. Our results suggested that high baseline serum uric acid levels within the normal range predict future development of metabolic syndrome after 3 y of follow-up.

  6. Fatty Acids and NLRP3 Inflammasome-Mediated Inflammation in Metabolic Tissues.

    Science.gov (United States)

    Ralston, Jessica C; Lyons, Claire L; Kennedy, Elaine B; Kirwan, Anna M; Roche, Helen M

    2017-08-21

    Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.

  7. A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia.

    Science.gov (United States)

    Asghari, Arvand; Marashi, Sayed-Amir; Ansari-Pour, Naser

    2017-04-01

    About 15% of couples experience difficulty in conceiving a child, of which half of the cases are thought to be male-related. Asthenozoospermia, or low sperm motility, is one of the frequent types of male infertility. Although energy metabolism is suggested to be central to the etiology of asthenozoospermia, very few attempts have been made to identify its underlying metabolic pathways. Here, we reconstructed SpermNet, the first proteome-scale model of the sperm cell by using whole-proteome data and the mCADRE algorithm. The reconstructed model was then analyzed using the COBRA toolbox. Genes were knocked-out in the model to investigate their effect on ATP production. A total of 78 genes elevated ATP production rate considerably of which most encode components of oxidative phosphorylation, fatty acid oxidation, the Krebs cycle, and members of the solute carrier 25 family. Among them, we identified 11 novel genes which have previously not been associated with sperm cell energy metabolism and may thus be implicated in asthenozoospermia. We further examined the reconstructed model by in silico knock out of currently known asthenozoospermia implicated-genes that were not predicted by our model. The pathways affected by knocking out these genes were also related to energy metabolism, confirming previous findings. Therefore, our model not only predicts the known pathways, it also identifies several non-glycolytic genes for deficient energy metabolism in asthenozoospermia. Finally, this model supports the notion that metabolic pathways besides glycolysis such as oxidative phosphorylation and fatty acid oxidation are essential for sperm energy metabolism and if validated, may form a basis for fertility recovery. mCADRE: metabolic context-specificity assessed by deterministic reaction evaluation; ATP: adenosine triphosphate; RNA: ribonucleic acid; FBA: flux balance analysis; FVA: flux variability analysis; DAVID: database for annotation, visualization and integrated

  8. Gene-Gene Interactions in the Folate Metabolic Pathway and the Risk of Conotruncal Heart Defects

    Directory of Open Access Journals (Sweden)

    Philip J. Lupo

    2010-01-01

    Full Text Available Conotruncal and related heart defects (CTRD are common, complex malformations. Although there are few established risk factors, there is evidence that genetic variation in the folate metabolic pathway influences CTRD risk. This study was undertaken to assess the association between inherited (i.e., case and maternal gene-gene interactions in this pathway and the risk of CTRD. Case-parent triads (n=727, ascertained from the Children's Hospital of Philadelphia, were genotyped for ten functional variants of nine folate metabolic genes. Analyses of inherited genotypes were consistent with the previously reported association between MTHFR A1298C and CTRD (adjusted P=.02, but provided no evidence that CTRD was associated with inherited gene-gene interactions. Analyses of the maternal genotypes provided evidence of a MTHFR C677T/CBS 844ins68 interaction and CTRD risk (unadjusted P=.02. This association is consistent with the effects of this genotype combination on folate-homocysteine biochemistry but remains to be confirmed in independent study populations.

  9. [Research on differentially expressed genes related to substance and energy metabolism between healthy volunteers and splenasthenic syndrome patients with chronic superficial gastritis].

    Science.gov (United States)

    Ze-Min, Yang; Wei-Wen, Chen; Ying-Fang, Wang

    2013-02-01

    To analyze the metabolic states of the lipids, protein, carbohydrate, and nucleic acid for chronic superficial gastritis patients of splenasthenic syndrome (SS), and to explore the pathogenesis mechanism of SS based on substance and energy metabolisms. During June 2004 to March 2005, recruited were four chronic superficial gastritis patients of SS who visited at the First Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Traditional Chinese Medicine. Four healthy volunteers were recruited from Guangzhou University of Chinese Medicine. Their gastric mucosa was extracted to perform experiments of DNA microarray. The dual-channel DNA microarray data were mined and bioinformatics analyzed by BRB ArrayTools and IPA software. Fifteen genes were involved in substance and energy metabolisms in 20 differentially expressed genes, accounting for 75%.Among these genes, one gene was up-regulated, 14 genes down-regulated, and 11 genes were enzyme gene. Differentially expressed genes related to lipid metabolism included ACAA2 and CYP20A1, manifested as fatty acid catabolism and cholesterol transformation. Genes related to protein metabolism included ALDH9A1, ASL, ASS1, PCY-OX1L, RPS28, UBE2D2, UBXN1, B3GNT1, GCNT1, and PPP1R3C, manifested as decreased amino acid metabolism that may affect the biologic processes such as autonomic nerve, urea cycle, etc., reduced protein synthesis, increased ubiquitination of fault fold proteins, and decreased post-translated modification of glycosylation and dephosphorylation. Genes related to carbohydrate metabolism included PPP1R3C, B3GNT1, and GCNT1, manifested as decreased glycogen and glycan syntheses. Genes related to nucleic acid metabolism included RMI1, SMARCD3, and PARP1, manifested as degraded DNA duplication and transcription, and increased DNA damage repair. The metabolisms of the lipids, protein, carbohydrate, and nucleic acid in chronic superficial gastritis patients of SS obviously decreased

  10. Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Chávez-Talavera, Oscar; Tailleux, Anne; Lefebvre, Philippe; Staels, Bart

    2017-05-01

    Bile acids are signaling molecules that coordinately regulate metabolism and inflammation via the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in bile acid, lipid and carbohydrate metabolism, energy expenditure, and inflammation by acting predominantly in enterohepatic tissues, but also in peripheral organs. In this review, we discuss the most recent findings on the inter-organ signaling and interplay with the gut microbiota of bile acids and their receptors in meta-inflammation, with a focus on their pathophysiologic roles in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic steatohepatitis, and their potential therapeutic applications. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    Science.gov (United States)

    Balaban, Seher; Lee, Lisa S.; Schreuder, Mark; Hoy, Andrew J.

    2015-01-01

    Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

  12. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    Directory of Open Access Journals (Sweden)

    Seher Balaban

    2015-01-01

    Full Text Available Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

  13. 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.

  14. Genome-wide gene expression changes in an industrial clavulanic acid overproduction strain of Streptomyces clavuligerus.

    Science.gov (United States)

    Medema, Marnix H; Alam, Mohammad T; Heijne, Wilbert H M; van den Berg, Marco A; Müller, Ulrike; Trefzer, Axel; Bovenberg, Roel A L; Breitling, Rainer; Takano, Eriko

    2011-03-01

    To increase production of the important pharmaceutical compound clavulanic acid, a β-lactamase inhibitor, both random mutagenesis approaches and rational engineering of Streptomyces clavuligerus strains have been extensively applied. Here, for the first time, we compared genome-wide gene expression of an industrial S. clavuligerus strain, obtained through iterative mutagenesis, with that of the wild-type strain. Intriguingly, we found that the majority of the changes contributed not to a complex rewiring of primary metabolism but consisted of a simple upregulation of various antibiotic biosynthesis gene clusters. A few additional transcriptional changes in primary metabolism at key points seem to divert metabolic fluxes to the biosynthetic precursors for clavulanic acid. In general, the observed changes largely coincide with genes that have been targeted by rational engineering in recent years, yet the presence of a number of previously unexplored genes clearly demonstrates that functional genomic analysis can provide new leads for strain improvement in biotechnology. © 2010 The Authors. Journal compilation © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  15. A Natural Light/Dark Cycle Regulation of Carbon-Nitrogen Metabolism and Gene Expression in Rice Shoots.

    Science.gov (United States)

    Li, Haixing; Liang, Zhijun; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei

    2016-01-01

    Light and temperature are two particularly important environmental cues for plant survival. Carbon and nitrogen are two essential macronutrients required for plant growth and development, and cellular carbon and nitrogen metabolism must be tightly coordinated. In order to understand how the natural light/dark cycle regulates carbon and nitrogen metabolism in rice plants, we analyzed the photosynthesis, key carbon-nitrogen metabolites, and enzyme activities, and differentially expressed genes and miRNAs involved in the carbon and nitrogen metabolic pathway in rice shoots at the following times: 2:00, 6:00, 10:00, 14:00, 18:00, and 22:00. Our results indicated that more CO2 was fixed into carbohydrates by a high net photosynthetic rate, respiratory rate, and stomatal conductance in the daytime. Although high levels of the nitrate reductase activity, free ammonium and carbohydrates were exhibited in the daytime, the protein synthesis was not significantly facilitated by the light and temperature. In mRNA sequencing, the carbon and nitrogen metabolism-related differentially expressed genes were obtained, which could be divided into eight groups: photosynthesis, TCA cycle, sugar transport, sugar metabolism, nitrogen transport, nitrogen reduction, amino acid metabolism, and nitrogen regulation. Additionally, a total of 78,306 alternative splicing events have been identified, which primarily belong to alternative 5' donor sites, alternative 3' acceptor sites, intron retention, and exon skipping. In sRNA sequencing, four carbon and nitrogen metabolism-related miRNAs (osa-miR1440b, osa-miR2876-5p, osa-miR1877 and osa-miR5799) were determined to be regulated by natural light/dark cycle. The expression level analysis showed that the four carbon and nitrogen metabolism-related miRNAs negatively regulated their target genes. These results may provide a good strategy to study how natural light/dark cycle regulates carbon and nitrogen metabolism to ensure plant growth and

  16. 'Trophic' and 'source' amino acids in trophic estimation: a likely metabolic explanation.

    Science.gov (United States)

    O'Connell, T C

    2017-06-01

    Amino acid nitrogen isotopic analysis is a relatively new method for estimating trophic position. It uses the isotopic difference between an individual's 'trophic' and 'source' amino acids to determine its trophic position. So far, there is no accepted explanation for the mechanism by which the isotopic signals in 'trophic' and 'source' amino acids arise. Yet without a metabolic understanding, the utility of nitrogen isotopic analyses as a method for probing trophic relations, at either bulk tissue or amino acid level, is limited. I draw on isotopic tracer studies of protein metabolism, together with a consideration of amino acid metabolic pathways, to suggest that the 'trophic'/'source' groupings have a fundamental metabolic origin, to do with the cycling of amino-nitrogen between amino acids. 'Trophic' amino acids are those whose amino-nitrogens are interchangeable, part of a metabolic amino-nitrogen pool, and 'source' amino acids are those whose amino-nitrogens are not interchangeable with the metabolic pool. Nitrogen isotopic values of 'trophic' amino acids will reflect an averaged isotopic signal of all such dietary amino acids, offset by the integrated effect of isotopic fractionation from nitrogen cycling, and modulated by metabolic and physiological effects. Isotopic values of 'source' amino acids will be more closely linked to those of equivalent dietary amino acids, but also modulated by metabolism and physiology. The complexity of nitrogen cycling suggests that a single identifiable value for 'trophic discrimination factors' is unlikely to exist. Greater consideration of physiology and metabolism should help in better understanding observed patterns in nitrogen isotopic values.

  17. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants)

    Energy Technology Data Exchange (ETDEWEB)

    Loewus, F.A. (Washington State Univ., Pullman, WA (United States). Inst. of Biological Chemistry); Seib, P.A. (Kansas State Univ., Manhattan, KS (United States). Dept. of Grain Science and Industry)

    1991-01-01

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  18. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants). Final report

    Energy Technology Data Exchange (ETDEWEB)

    Loewus, F.A. [Washington State Univ., Pullman, WA (United States). Inst. of Biological Chemistry; Seib, P.A. [Kansas State Univ., Manhattan, KS (United States). Dept. of Grain Science and Industry

    1991-12-31

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  19. Metabolic Effects of a Succinic Acid

    Directory of Open Access Journals (Sweden)

    B. N. Shakh

    2014-01-01

    Full Text Available The paper discusses promises for clinical use of substrate antihypoxants.Objective: to investigate the efficacy of succinate containing  substrate  antihypoxants  on  systemic  oxygen  consumption,  blood  buffer  capacity,  and  changes  in  the  mixed venous blood level of lactate when they are used in gravely sick patients and victims with marked metabolic posthypoxic disorders.Subjects and methods. The trial enrolled 30 patients and victims who had sustained an episode of severe hypoxia of mixed genesis, the severity of which was evaluated by the APACHE II scale and amounted to 23 to 30 scores with a 46 to 70.3% risk of death. The standard infusion program in this group involved the succinate-containing drug 1.5% reamberin solution  in  a  total  dose  of  800  ml.  A  comparison  group  included  15  patients  who  had  undergone  emergency  extensive surgery for abdominal diseases. 400 ml of 10% glucose solution was used as an infusion medium. Oxygen consumption (VO2ml/min and carbon dioxide production (VCO2ml/min were measured before infusion and monitored for 2 hours. Arterial blood gases and acid-base balance (ABB parameters and mixed venous blood lactate levels were examined. Measurements were made before and 30 minutes after the infusion of reamberin or glucose solution.Results. Infusion of 1.5% reamberin solution was followed by a significant increase in minute oxygen consumption from 281.5±21.2 to 310.4±24.4 ml/min. CO2 production declined (on average, from 223.3±6.5 to 206.5±7.59 ml/min. During infusion of 10% glucose solution, all the patients of the comparison group showed a rise in oxygen consumption from 303.6±33.86 to 443.13±32.1 ml/min, i.e. about 1.5-fold. VCO2 changed similarly. The intravenous infusion of 800 ml of 1.5% reamberin solution raised arterial blood buffer capacity, which was reflected by changes in pH, BE, and HCO3. There was a clear trend for lactate values to drop in the

  20. Metatranscriptomic analysis of lactic acid bacterial gene expression during kimchi fermentation.

    Science.gov (United States)

    Jung, Ji Young; Lee, Se Hee; Jin, Hyun Mi; Hahn, Yoonsoo; Madsen, Eugene L; Jeon, Che Ok

    2013-05-15

    Barcode-based 16S rRNA gene pyrosequencing showed that the kimchi microbiome was dominated by six lactic acid bacteria (LAB), Leuconostoc (Lc.) mesenteroides, Lactobacillus (Lb.) sakei, Weissella (W.) koreensis, Lc. gelidum, Lc. carnosum, and Lc. gasicomitatum. Therefore, we used completed genome sequences of representatives of these bacteria to investigate metatranscriptomic gene-expression profiles during kimchi fermentation. Total mRNA was extracted from kimchi samples taken at five time points during a 29 day-fermentation. Nearly all (97.7%) of the metagenome sequences that were recruited on all LAB genomes of GenBank mapped onto the six LAB strains; this high coverage rate indicated that this approach for assessing processes carried out by the kimchi microbiome was valid. Expressed mRNA sequences (as cDNA) were determined using Illumina GA IIx. Assignment of mRNA sequences to metabolic genes using MG-RAST revealed the prevalence of carbohydrate metabolism and lactic acid fermentation. The mRNA sequencing reads were mapped onto genomes of the six LAB strains, which showed that Lc. mesenteroides was most active during the early-stage fermentation, whereas gene expression by Lb. sakei and W. koreensis was high during later stages. However, gene expression by Lb. sakei decreased rapidly at 25 days of fermentation, which was possibly caused by bacteriophage infection of the Lactobacillus species. Many genes related to carbohydrate transport and hydrolysis and lactate fermentation were actively expressed, which indicated typical heterolactic acid fermentation. Mannitol dehydrogenase-encoding genes (mdh) were identified from all Leuconostoc species and especially Lc. mesenteroides, which harbored three copies (two copies on chromosome and one copy on plasmid) of mdh with different expression patterns. These results contribute to knowledge of the active populations and gene expression in the LAB community responsible for an important fermentation process. Copyright

  1. Regulation of Phosphoenolpyruvate Carboxylase and Crassulacean Acid Metabolism Induction in Mesembryanthemum crystallinum L. by Cytokinin 1

    Science.gov (United States)

    Schmitt, Jürgen M.; Piepenbrock, Mechtild

    1992-01-01

    Phosphoenolpyruvate carboxylase (PEPCase), the key enzyme of Crassulacean acid metabolism, is induced by water stress in leaves of Mesembryanthemum crystallinum. In water-stressed plants or excised leaves, exogenous cytokinin suppresses PEPCase transcript accumulation in the leaves. Cytokinin (6-benzylaminopurine) used in concentrations from 5 to 500 micromolar (a) inhibits the upregulation of PEPCase transcripts, enzyme activity, and Crassulacean acid metabolism induction in salt-stressed intact plants when sprayed once daily during the stress period, (b) inhibits the accumulation of PEPCase mRNA in leaves from well-watered plants, (c) down-regulates PEPCase transcripts within 8 hours in prestressed, intact plants after a single spraying of an individual leaf, (d) inhibits accumulation of PEPCase transcripts in excised, wilting leaves, and (e) accelerates the net decrease of PEPCase transcripts in excised leaves from prestressed plants under rehydration conditions. When roots, the main site of cytokinin biosynthesis, are excised, PEPCase induction under drought stress is intensified. We propose that roots, acting as sensors of soil water status, may regulate PEPCase gene expression in the leaves with cytokinin as a signal transducer. ImagesFigure 2Figure 7 PMID:16669088

  2. Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Duparc, Thibaut; Plovier, Hubert; Marrachelli, Vannina G

    2017-01-01

    performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). RESULTS...... proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes...

  3. Adipose tissue arachidonic acid and the metabolic syndrome in Costa Rican adults.

    Science.gov (United States)

    Williams, Eric S; Baylin, Ana; Campos, Hannia

    2007-08-01

    Arachidonic acid, a precursor to a series of inflammatory mediators, may contribute to the development of insulin resistance. We examined the association between adipose tissue arachidonic acid and the metabolic syndrome in Costa Rica, a country in which the metabolic syndrome is highly prevalent. The 484 study participants each provided a fasting blood sample and an adipose tissue biopsy that was analyzed for fatty acid composition. Criteria for the metabolic syndrome were those established in the Third Report of the National Cholesterol Education Program Expert Panel. The data were analyzed by multivariate logistic regression. Subjects with greater adipose tissue arachidonic acid content had an increasing risk of the metabolic syndrome across quintiles: odds ratio (95% confidence interval), 1.00; 1.51 (0.78-2.91); 2.40 (1.26-4.55); 3.50 (1.84-6.66); and 6.01 (3.11-11.61); test for trend, P<0.0001, after adjustment for age, gender and area of residence. Further adjustment for metabolic risk factors, including adipose fatty acids and body mass index, did not significantly modify the result. Adipose tissue arachidonic acid was also independently associated with abdominal obesity, hypertriglyceridemia, elevated fasting glucose, and high blood pressure. This study identifies arachidonic acid as an important independent marker of metabolic dysregulation. A better understanding of the role of this fatty acid in the pathogenesis of the metabolic syndrome is warranted.

  4. Gene regulation of lipid and phospholipid metabolism in Atlantic cod (Gadus morhua) larvae.

    Science.gov (United States)

    Li, Keshuai; Østensen, Mari-Ann; Attramadal, Kari; Winge, Per; Sparstad, Torfinn; Bones, Atle M; Vadstein, Olav; Kjørsvik, Elin; Olsen, Yngvar

    2015-12-01

    The mechanism of essentiality of dietary phospholipid (PL) for larval fish is not clear. The main objective of the present study was to determine if the PL requirement of Atlantic cod larvae was due to any genetic impairment caused by functional immaturity. Cod larvae were sampled at 1, 3, 8, 13, 17, 18, 30, 42 and 60 days post hatch (dph) for transcriptome analysis using a recently developed microarray. The fatty acid profile and gene expression levels of cod larvae at 17 dph were compared after feeding differently enriched rotifers, which contained different DHA levels in PL. No significant differences (pcod larvae, their growth and survival, and their DHA levels in total lipid and PL fraction. The fatty acid data suggested that dietary EPA was elongated to DPA by cod larvae, and a threshold DHA level in PL to maintain membrane fluidity and other functions may exist. There appeared to be no major effect of development on the expression of key genes of PL biosynthesis suggesting no genetic constrain in early developmental stages. Our overall data suggested that besides the possible limited de novo PC synthesis ability in the intestine, other metabolic constraints should also be considered, especially the possible low input of bile PC as a result of immature liver. Further studies are needed to elucidate the gene expression level and enzyme activity in the PL biosynthesis pathways for specific tissue or cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Differential effect of fructose on fat metabolism and clock gene expression in hepatocytes vs. myotubes.

    Science.gov (United States)

    Chapnik, Nava; Rozenblit-Susan, Sigal; Genzer, Yoni; Froy, Oren

    2016-08-01

    In the liver, fructose bypasses the main rate-limiting step of glycolysis at the level of phosphofructokinase, allowing it to act as an unregulated substrate for de novo lipogenesis. It has been reported that consumption of large amounts of fructose increases de novo lipogenesis in the liver. However, the effect of fructose on ectopic deposition of muscle fat has been under dispute. Our aim was to study the effect of fructose on levels of genes and proteins involved in fatty acid oxidation and synthesis in hepatocytes vs. muscle cells. In addition, as fat accumulation leads to disruption of daily rhythms, we tested the effect of fructose treatment on clock gene expression. AML-12 hepatocytes and C2C12 myotubes were treated with fructose or glucose for 2 consecutive 24-h cycles and harvested every 6h. In contrast to glucose, fructose disrupted clock gene rhythms in hepatocytes, but in myotubes, it led to more robust rhythms. Fructose led to low levels of phosphorylated AMP-activated protein kinase (pAMPK) and high levels of LIPIN1 in hepatocytes compared with glucose. In contrast, fructose led to high pAMPK and low LIPIN1 and microsomal triacylglycerol transfer protein (MTTP) levels in myotubes compared with glucose. Analysis of fat content revealed that fructose led to less fat accumulation in myotubes compared to hepatocytes. In summary, fructose shifts metabolism towards fatty acid synthesis and clock disruption in hepatocytes, but not in myotubes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. L-Lactic acid production from glycerol coupled with acetic acid metabolism by Enterococcus faecalis without carbon loss.

    Science.gov (United States)

    Murakami, Nao; Oba, Mana; Iwamoto, Mariko; Tashiro, Yukihiro; Noguchi, Takuya; Bonkohara, Kaori; Abdel-Rahman, Mohamed Ali; Zendo, Takeshi; Shimoda, Mitsuya; Sakai, Kenji; Sonomoto, Kenji

    2016-01-01

    Glycerol is a by-product in the biodiesel production process and considered as one of the prospective carbon sources for microbial fermentation including lactic acid fermentation, which has received considerable interest due to its potential application. Enterococcus faecalis isolated in our laboratory produced optically pure L-lactic acid from glycerol in the presence of acetic acid. Gas chromatography-mass spectrometry analysis using [1, 2-(13)C2] acetic acid proved that the E. faecalis strain QU 11 was capable of converting acetic acid to ethanol during lactic acid fermentation of glycerol. This indicated that strain QU 11 restored the redox balance by oxidizing excess NADH though acetic acid metabolism, during ethanol production, which resulted in lactic acid production from glycerol. The effects of pH control and substrate concentration on lactic acid fermentation were also investigated. Glycerol and acetic acid concentrations of 30 g/L and 10 g/L, respectively, were expected to be appropriate for lactic acid fermentation of glycerol by strain QU 11 at a pH of 6.5. Furthermore, fed-batch fermentation with 30 g/L glycerol and 10 g/L acetic acid wholly exhibited the best performance including lactic acid production (55.3 g/L), lactic acid yield (0.991 mol-lactic acid/mol-glycerol), total yield [1.08 mol-(lactic acid and ethanol)]/mol-(glycerol and acetic acid)], and total carbon yield [1.06 C-mol-(lactic acid and ethanol)/C-mol-(glycerol and acetic acid)] of lactic acid and ethanol. In summary, the strain QU 11 successfully produced lactic acid from glycerol with acetic acid metabolism, and an efficient fermentation system was established without carbon loss. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. The role of uric acid in metabolic syndrome in patients with psoriasis

    Directory of Open Access Journals (Sweden)

    Berna Solak

    2017-06-01

    Full Text Available Background and Design: Psoriasis patients have increased risk of obesity, metabolic syndrome and cardiovascular disease. Uric acid is a metabolic marker associated with metabolic syndrome and cardiovascular diseases. Uric acid levels increase in psoriasis as well. The aim of this study was to investigate the role of uric acid in metabolic syndrome in patients with psoriasis. Materials and Methods: Chronic plaque psoriasis patients who presented to the dermatology outpatient clinics in a university-affiliated training and research hospital and age- and gender-matched healthy individuals were included in the study. Waist circumference, height and weight measurements in both groups were recorded, and body mass index was calculated. Serum uric acid, urea, creatinine, C-reactive protein, fasting blood glucose, high-density lipoprotein cholesterol, total cholesterol, triglyceride and insulin levels were determined. Metabolic syndrome and insulin resistance status were evaluated. The findings were compared statistically. Results: Seventy patients with chronic plaque psoriasis (37 females, 33 males and 60 healthy individuals (31 females, 29 males were included in the study. The prevalence of metabolic syndrome and uric acid levels were found to be higher in the psoriasis group than in control group (p=0.003 and p=0.008, respectively. Serum uric acid levels and Psoriasis Area and Severity Index scores were higher in psoriasis patients with metabolic syndrome than in those without metabolic syndrome when psoriasis patients were evaluated separately (p=0.041, p=0.024, respectively. A positive correlation was observed between abdominal circumference and serum uric acid levels in psoriasis patients (p=0.003, r=0.350 Conclusion: The results of this study show that uric acid levels are elevated in psoriasis patients with metabolic syndrome. The prevalence of metabolic syndrome was also significantly higher. Hence, patients should be followed up for development

  8. Gene Targeting and Expression Modulation by Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    Peptide nucleic acids (PNA) are artificial structural mimics of nucleic acids capable of sequence specific hybridization to both RNA and DNA. Thus they have obvious potential as gene targeting agents for drug discovery approaches. An overview with emphasis on recent progress on RNA "interference"...

  9. Gene cloning of phenolic acid decarboxylase from Bacillus subtilis ...

    African Journals Online (AJOL)

    Phenolic acid decarboxylase (PADC) gene, encoding phenolic acid decarboxylase, was cloned from Bacillus subtilis and ligated with a shuttle vector YEp352 to generate a novel plasmid YPADC. By analysis of sequencing and the restriction endonuclease digestion, the validity of construction was proved. Subsequently ...

  10. Disturbances of water, electrolyte and acid-base metabolism in ...

    African Journals Online (AJOL)

    Chantel

    hyperkalaemia. Brain metabolism and the regulation of its volume are impaired, resulting in progressive cen- tral nervous system depression and coma. The anion gap can be calculated as follows:2 .... ing metabolic acidosis, especially in children. Metabolic acidosis ... breathing room air a rise in PaCO2 will cause a fall in ...

  11. Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase.

    Science.gov (United States)

    Bartelt, Alexander; Koehne, Till; Tödter, Klaus; Reimer, Rudolph; Müller, Brigitte; Behler-Janbeck, Friederike; Heeren, Joerg; Scheja, Ludger; Niemeier, Andreas

    2017-06-13

    Adipocytes are master regulators of energy homeostasis. Although the contributions of classical brown and white adipose tissue (BAT and WAT, respectively) to glucose and fatty acid metabolism are well characterized, the metabolic role of adipocytes in bone marrow remains largely unclear. Here, we quantify bone fatty acid metabolism and its contribution to systemic nutrient handling in mice. Whereas in parts of the skeleton the specific amount of nutrients taken-up from the circulation was lower than in other metabolically active tissues such as BAT or liver, the overall contribution of the skeleton as a whole organ was remarkable, placing it among the top organs involved in systemic glucose as well as fatty acid clearance. We show that there are considerable site-specific variations in bone marrow fatty acid composition throughout the skeleton and that, especially in the tibia, marrow fatty acid profiles resemble classical BAT and WAT. Using a mouse model lacking lipoprotein lipase (LPL), a master regulator of plasma lipid turnover specifically in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone. Notably, these changes in fatty acid profiles were not associated with any gross skeletal phenotype. These results identify LPL as an important regulator of fatty acid transport to skeletal compartments and demonstrate an intricate functional link between systemic and skeletal fatty acid and glucose metabolism.

  12. Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase

    Directory of Open Access Journals (Sweden)

    Alexander Bartelt

    2017-06-01

    Full Text Available Adipocytes are master regulators of energy homeostasis. Although the contributions of classical brown and white adipose tissue (BAT and WAT, respectively to glucose and fatty acid metabolism are well characterized, the metabolic role of adipocytes in bone marrow remains largely unclear. Here, we quantify bone fatty acid metabolism and its contribution to systemic nutrient handling in mice. Whereas in parts of the skeleton the specific amount of nutrients taken-up from the circulation was lower than in other metabolically active tissues such as BAT or liver, the overall contribution of the skeleton as a whole organ was remarkable, placing it among the top organs involved in systemic glucose as well as fatty acid clearance. We show that there are considerable site-specific variations in bone marrow fatty acid composition throughout the skeleton and that, especially in the tibia, marrow fatty acid profiles resemble classical BAT and WAT. Using a mouse model lacking lipoprotein lipase (LPL, a master regulator of plasma lipid turnover specifically in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone. Notably, these changes in fatty acid profiles were not associated with any gross skeletal phenotype. These results identify LPL as an important regulator of fatty acid transport to skeletal compartments and demonstrate an intricate functional link between systemic and skeletal fatty acid and glucose metabolism.

  13. The impact of polymorphisms in P-gp, DNA repair and folic acid metabolism genes in newly diagnosed multiple myeloma patients treated with thalidomide plus dexamethasone, with or without bortezomib

    OpenAIRE

    Lyzbicki, Barnaba

    2012-01-01

    The principle aim of this study was to investigate biological predictors of response and resistance to multiple myeloma treatment. Two hypothesis had been proposed as responsible of responsiveness: SNPs in DNA repair and Folate pathway, and P-gp dependent efflux. As a first objective, panel of SNPs in DNA repair and Folate pathway genes, were analyzed. It was a retrospective study in a group of 454, previously untreated, MM patients enrolled in a randomized phase III open-label study. Res...

  14. Influence of neonatal hypothyroidism on hepatic gene expression and lipid metabolism in adulthood.

    Directory of Open Access Journals (Sweden)

    Ruymán Santana-Farré

    Full Text Available Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood.

  15. Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

    Science.gov (United States)

    Bocos, Carlos; Henríquez-Hernández, Luis A.; Kahlon, Nusrat; Herrera, Emilio; Norstedt, Gunnar; Parini, Paolo; Flores-Morales, Amilcar; Fernández-Pérez, Leandro

    2012-01-01

    Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. PMID:22666351

  16. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

    Science.gov (United States)

    2010-01-01

    Background Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome. Results CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Conclusions Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie. PMID:20459735

  17. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

    Directory of Open Access Journals (Sweden)

    Byrne Kevin P

    2010-05-01

    Full Text Available Abstract Background Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB, an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1 and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae. Saccharomyces cerevisiae is also included as a reference genome. Results CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Conclusions Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie.

  18. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser.

    Science.gov (United States)

    Fitzpatrick, David A; O'Gaora, Peadar; Byrne, Kevin P; Butler, Geraldine

    2010-05-10

    Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome. CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie.

  19. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

    LENUS (Irish Health Repository)

    Fitzpatrick, David A

    2010-05-10

    Abstract Background Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome. Results CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging\\/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Conclusions Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http:\\/\\/cgob.ucd.ie.

  20. Diversity and Evolutionary History of Iron Metabolism Genes in Diatoms.

    Directory of Open Access Journals (Sweden)

    Ryan D Groussman

    Full Text Available Ferroproteins arose early in Earth's history, prior to the emergence of oxygenic photosynthesis and the subsequent reduction of bioavailable iron. Today, iron availability limits primary productivity in about 30% of the world's oceans. Diatoms, responsible for nearly half of oceanic primary production, have evolved molecular strategies for coping with variable iron concentrations. Our understanding of the evolutionary breadth of these strategies has been restricted by the limited number of species for which molecular sequence data is available. To uncover the diversity of strategies marine diatoms employ to meet cellular iron demands, we analyzed 367 newly released marine microbial eukaryotic transcriptomes, which include 47 diatom species. We focused on genes encoding proteins previously identified as having a role in iron management: iron uptake (high-affinity ferric reductase, multi-copper oxidase, and Fe(III permease; iron storage (ferritin; iron-induced protein substitutions (flavodoxin/ferredoxin, and plastocyanin/cytochrome c6 and defense against reactive oxygen species (superoxide dismutases. Homologs encoding the high-affinity iron uptake system components were detected across the four diatom Classes suggesting an ancient origin for this pathway. Ferritin transcripts were also detected in all Classes, revealing a more widespread utilization of ferritin throughout diatoms than previously recognized. Flavodoxin and plastocyanin transcripts indicate possible alternative redox metal strategies. Predicted localization signals for ferredoxin identify multiple examples of gene transfer from the plastid to the nuclear genome. Transcripts encoding four superoxide dismutase metalloforms were detected, including a putative nickel-coordinating isozyme. Taken together, our results suggest that the majority of iron metabolism genes in diatoms appear to be vertically inherited with functional diversity achieved via possible neofunctionalization of

  1. Transcriptome analysis of acetic-acid-treated yeast cells identifies a large set of genes whose overexpression or deletion enhances acetic acid tolerance.

    Science.gov (United States)

    Lee, Yeji; Nasution, Olviyani; Choi, Eunyong; Choi, In-Geol; Kim, Wankee; Choi, Wonja

    2015-08-01

    Acetic acid inhibits the metabolic activities of Saccharomyces cerevisiae. Therefore, a better understanding of how S. cerevisiae cells acquire the tolerance to acetic acid is of importance to develop robust yeast strains to be used in industry. To do this, we examined the transcriptional changes that occur at 12 h post-exposure to acetic acid, revealing that 56 and 58 genes were upregulated and downregulated, respectively. Functional categorization of them revealed that 22 protein synthesis genes and 14 stress response genes constituted the largest portion of the upregulated and downregulated genes, respectively. To evaluate the association of the regulated genes with acetic acid tolerance, 3 upregulated genes (DBP2, ASC1, and GND1) were selected among 34 non-protein synthesis genes, and 54 viable mutants individually deleted for the downregulated genes were retrieved from the non-essential haploid deletion library. Strains overexpressing ASC1 and GND1 displayed enhanced tolerance to acetic acid, whereas a strain overexpressing DBP2 was sensitive. Fifty of 54 deletion mutants displayed enhanced acetic acid tolerance. Three chosen deletion mutants (hsps82Δ, ato2Δ, and ssa3Δ) were also tolerant to benzoic acid but not propionic and sorbic acids. Moreover, all those five (two overexpressing and three deleted) strains were more efficient in proton efflux and lower in membrane permeability and internal hydrogen peroxide content than controls. Individually or in combination, those physiological changes are likely to contribute at least in part to enhanced acetic acid tolerance. Overall, information of our transcriptional profile was very useful to identify molecular factors associated with acetic acid tolerance.

  2. Unraveling new genes associated with seed development and metabolism in Bixa orellana L. by expressed sequence tag (EST) analysis.

    Science.gov (United States)

    Soares, Virgínia L F; Rodrigues, Simone M; de Oliveira, Tahise M; de Queiroz, Talisson O; Lima, Lívia S; Hora-Júnior, Braz T; Gramacho, Karina P; Micheli, Fabienne; Cascardo, Júlio C M; Otoni, Wagner C; Gesteira, Abelmon S; Costa, Marcio G C

    2011-02-01

    The tropical tree Bixa orellana L. produces a range of secondary metabolites which biochemical and molecular biosynthesis basis are not well understood. In this work we have characterized a set of ESTs from a non-normalized cDNA library of B. orellana seeds to obtain information about the main developmental and metabolic processes taking place in developing seeds and their associated genes. After sequencing a set of randomly selected clones, most of the sequences were assigned with putative functions based on similarity, GO annotations and protein domains. The most abundant transcripts encoded proteins associated with cell wall (prolyl 4-hydroxylase), fatty acid (acyl carrier protein), and hormone/flavonoid (2OG-Fe oxygenase) synthesis, germination (MADS FLC-like protein) and embryo development (AP2/ERF transcription factor) regulation, photosynthesis (chlorophyll a-b binding protein), cell elongation (MAP65-1a), and stress responses (metallothionein- and thaumatin-like proteins). Enzymes were assigned to 16 different metabolic pathways related to both primary and secondary metabolisms. Characterization of two candidate genes of the bixin biosynthetic pathway, BoCCD and BoOMT, showed that they belong, respectively, to the carotenoid-cleavage dioxygenase 4 (CCD4) and caffeic acid O-methyltransferase (COMT) families, and are up-regulated during seed development. It indicates their involvement in the synthesis of this commercially important carotenoid pigment in seeds of B. orellana. Most of the genes identified here are the first representatives of their gene families in B. orellana.

  3. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

    DEFF Research Database (Denmark)

    Wahlström, Annika; Sayin, Sama I; Marschall, Hanns-Ulrich

    2016-01-01

    The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is pr...... by altered microbiota composition.......The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids......, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host...

  4. Association of metabolic gene polymorphisms with tobacco consumption in healthy controls.

    NARCIS (Netherlands)

    Smits, K.M.; Benhamou, S.; Garte, S.; Weijenberg, M.P.; Alamanos, Y.; Ambrosone, C.; Autrup, H.; Autrup, J.L.; Baranova, H.; Bathum, L.; Boffetta, P.; Bouchardy, C.; Brockmoller, J.; Butkiewicz, D.; Cascorbi, I.; Clapper, M.L.; Coutelle, C.; Daly, A.; Muzi, G.; Dolzan, V.; Duzhak, T.G.; Farker, K.; Golka, K.; Haugen, A.; Hein, D.W.; Hildesheim, A.; Hirvonen, A.; Hsieh, L.L.; Ingelman-Sundberg, M.; Kalina, I.; Kang, D.; Katoh, T.; Kihara, M.; Ono-Kihara, M.; Kim, H.L.; Kiyohara, C.; Kremers, P.; Lazarus, P.; Marchand, L. le; Lechner, M.C.; London, S.; Manni, J.J.; Maugard, C.M.; Morgan, G.J.; Morita, S.; Nazar-Stewart, V.; Kristensen, V.N.; Oda, Y.; Parl, F.F.; Peters, W.H.M.; Rannug, A.; Rebbeck, T.; Pinto, L.F.; Risch, A.; Romkes, M.; Salagovic, J.; Schoket, B.; Seidegard, J.; Shields, P.G.; Sim, E.; Sinnett, D.; Strange, R.C.; Stucker, I.; Sugimura, H.; To-Figueras, J.; Vineis, P.; Yu, M.C.; Zheng, W.; Pedotti, P.; Taioli, E.

    2004-01-01

    Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the

  5. Effect of para-chlorophenoxyacetic acid on acid invertase gene ...

    African Journals Online (AJOL)

    Tomato cv. Liaoyuanduoli (Solanum lycopersicum) plants were cultivated in a greenhouse to allow sampling of the second fruit in the first cluster and comparison with tomato fruit that developed following para-chlorophenoxyacetic acid (PCPA) treatment. Sugar content, activities of sugar related enzymes and the effects of ...

  6. Expanding metabolic pathway for de novo biosynthesis of the chiral pharmaceutical intermediate L-pipecolic acid in Escherichia coli.

    Science.gov (United States)

    Ying, Hanxiao; Tao, Sha; Wang, Jing; Ma, Weichao; Chen, Kequan; Wang, Xin; Ouyang, Pingkai

    2017-03-27

    The six-carbon circular non-proteinogenic compound L-pipecolic acid is an important chiral drug intermediate with many applications in the pharmaceutical industry. In the present study, we developed a metabolically engineered strain of Escherichia coli for the overproduction of L-pipecolic acid from glucose. The metabolic pathway from L-lysine to L-pipecolic acid was constructed initially by introducing lysine cyclodeaminase (LCD). Next, L-lysine metabolic flux from glucose was amplified by the plasmid-based overexpression of dapA, lysC, and lysA under the control of the strong trc promoter to increase the biosynthetic pool of the precursor L-lysine. Additionally, since the catalytic efficiency of the key enzyme LCD is limited by the cofactor NAD(+), the intracellular pyridine nucleotide concentration was rebalanced by expressing the pntAB gene encoding the transhydrogenase, which elevated the proportion of LCD with bound NAD(+) and enhanced L-pipecolic acid production significantly. Further, optimization of Fe(2+) and surfactant in the fermentation process resulted in 5.33 g/L L-pipecolic acid, with a yield of 0.13 g/g of glucose via fed-batch cultivation. We expanded the metabolic pathway for the synthesis of the chiral pharmaceutical intermediate L-pipecolic acid in E. coli. Using the engineered E. coli, a fast and efficient fermentative production of L-pipecolic acid was achieved. This strategy could be applied to the biosynthesis of other commercially and industrially important chiral compounds containing piperidine rings.

  7. Adaptation of Intestinal and Bile Acid Physiology Accompany the Metabolic Benefits Following Ileal Interposition in the Rat.

    Science.gov (United States)

    Zhao, Ping; Wendt, Donna; Goodin, Sean Z; Ravichandran, Shwetha; Chouinard, Tara E; Strader, April D

    2017-08-31

    Ileal interposition recapitulates many of the metabolic improvements similar to Roux-en-Y gastric bypass. We aimed to determine whether the metabolic improvements seen following ileal interposition were conferred solely by the interposed segment by examining changes in neighboring intestinal segments as well as the composition of the bile acid pool. Adult male rats were treated with either sham or ileal interposition surgeries. Glucose tolerance tests, body composition analysis, polymer chain reaction, enzyme-linked immunosorbent assay, and mass spectrometry were done after the surgeries. This study showed that ileal interposition improved glucose tolerance and enhanced both fasting and glucose-stimulated GLP-1 secretion in diabetic rats. Total bile acid pool was similar between groups but the composition favored glycine-conjugation in rats with ileal interposition. Insulin secretion was highly correlated with the 12-alpha-hydroxylase index of activity. The interposed ileum exhibited an increase in mRNA for preproglucagon and peptide YY; however, the bile acid transporter, apical sodium bile acid transporter, was dramatically reduced compared to sham rats. The interposed segment becomes jejunized in its new location as indicated by an increase in Glut2 and Pepck mRNA, genes predominantly synthesized within the jejunum. Ileal relocation alone can significantly alter the bile acid pool to favor a more insulin-sensitive metabolism in association with intestinal wide alterations in mRNA for a variety of genes. Ileal interposition may confer metabolic improvement via both the interposed segment and the associated intestinal changes in all segments of the intestine, including the colon.

  8. Codon usage and amino acid usage influence genes expression level.

    Science.gov (United States)

    Paul, Prosenjit; Malakar, Arup Kumar; Chakraborty, Supriyo

    2018-02-01

    Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

  9. Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

    Science.gov (United States)

    Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-07-01

    It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Gene expression analyses reveal metabolic specifications in acute O2 -sensing chemoreceptor cells.

    Science.gov (United States)

    Gao, Lin; Bonilla-Henao, Victoria; García-Flores, Paula; Arias-Mayenco, Ignacio; Ortega-Sáenz, Patricia; López-Barneo, José

    2017-09-15

    Glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM) are essential for reflex cardiorespiratory adaptation to hypoxia. However, the mechanisms whereby these cells detect changes in O2 tension are poorly understood. The metabolic properties of acute O2 -sensing cells have been investigated by comparing the transcriptomes of CB and AM cells, which are O2 -sensitive, with superior cervical ganglion neurons, which are practically O2 -insensitive. In O2 -sensitive cells, we found a characteristic prolyl hydroxylase 3 down-regulation and hypoxia inducible factor 2α up-regulation, as well as overexpression of genes coding for three atypical mitochondrial electron transport subunits and pyruvate carboxylase, an enzyme that replenishes tricarboxylic acid cycle intermediates. In agreement with this observation, the inhibition of succinate dehydrogenase impairs CB acute O2 sensing. The responsiveness of peripheral chemoreceptor cells to acute hypoxia depends on a 'signature metabolic profile'. Acute O2 sensing is a fundamental property of cells in the peripheral chemoreceptors, e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM), and is necessary for adaptation to hypoxia. These cells contain O2 -sensitive ion channels, which mediate membrane depolarization and transmitter release upon exposure to hypoxia. However, the mechanisms underlying the detection of changes in O2 tension by cells are still poorly understood. Recently, we suggested that CB glomus cells have specific metabolic features that favour the accumulation of reduced quinone and the production of mitochondrial NADH and reactive oxygen species during hypoxia. These signals alter membrane ion channel activity. To investigate the metabolic profile characteristic of acute O2 -sensing cells, we used adult mice to compare the transcriptomes of three cell types derived from common sympathoadrenal progenitors, but exhibiting variable

  11. Analysis of L-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli.

    Science.gov (United States)

    Nishio, Yousuke; Ogishima, Soichi; Ichikawa, Masao; Yamada, Yohei; Usuda, Yoshihiro; Masuda, Tadashi; Tanaka, Hiroshi

    2013-09-22

    Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. We constructed an L-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for L-glutamic acid production; the results of this process corresponded with previous experimental data regarding L-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of L-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model L-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in L-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation.

  12. Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling.

    Science.gov (United States)

    Bénit, Paule; Letouzé, Eric; Rak, Malgorzata; Aubry, Laetitia; Burnichon, Nelly; Favier, Judith; Gimenez-Roqueplo, Anne-Paule; Rustin, Pierre

    2014-08-01

    Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonetheless, the most striking observations have been made in the recent period while investigating human diseases, especially a set of specific cancers, revealing the crucial role of Krebs cycle intermediates as factors affecting genes methylation and thus cell remodeling. We review here the recent advances and persisting incognita about the role of Krebs cycle acids in diverse aspects of cellular life and human pathology. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Human nutrigenomics of gene regulation by dietary fatty acids

    NARCIS (Netherlands)

    Afman, L.A.; Muller, M.R.

    2012-01-01

    Nutrigenomics employs high-throughput genomics technologies to unravel how nutrients modulate gene and protein expression and ultimately influence cellular and organism metabolism. The most often-applied genomics technique so far is transcriptomics, which allows quantifying genome-wide changes in

  14. Metabolic solutions to the biosynthesis of some diaminomonocarboxylic acids in nature: Formation in cyanobacteria of the neurotoxins 3-N-methyl-2,3-diaminopropanoic acid (BMAA) and 2,4-diaminobutanoic acid (2,4-DAB).

    Science.gov (United States)

    Nunn, Peter B; Codd, Geoffrey A

    2017-12-01

    The non-encoded diaminomonocarboxylic acids, 3-N-methyl-2,3-diaminopropanoic acid (syn: α-amino-β-methylaminopropionic acid, MeDAP; β-N-methylaminoalanine, BMAA) and 2,4-diaminobutanoic acid (2,4-DAB), are distributed widely in cyanobacterial species in free and bound forms. Both amino acids are neurotoxic in whole animal and cell-based bioassays. The biosynthetic pathway to 2,4-DAB is well documented in bacteria and in one higher plant species, but has not been confirmed in cyanobacteria. The biosynthetic pathway to BMAA is unknown. This review considers possible metabolic routes, by analogy with reactions used in other species, by which these amino acids might be biosynthesised by cyanobacteria, which are a widespread potential environmental source of these neurotoxins. Where possible, the gene expression that might be implicated in these biosyntheses is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism.

    Science.gov (United States)

    Kang, Hong Soon; Angers, Martin; Beak, Ju Youn; Wu, Xiying; Gimble, Jeffrey M; Wada, Taira; Xie, Wen; Collins, Jennifer B; Grissom, Sherry F; Jetten, Anton M

    2007-10-22

    Retinoid-related orphan receptors alpha (ROR alpha) and gamma (ROR gamma) are both expressed in liver; however, their physiological functions in this tissue have not yet been clearly defined. The ROR alpha1 and ROR gamma 1 isoforms, but not ROR alpha 4, show an oscillatory pattern of expression during circadian rhythm. To obtain insight into the physiological functions of ROR receptors in liver, we analyzed the gene expression profiles of livers from WT, ROR alpha-deficient staggerer (sg) mice (ROR alpha(sg/sg)), ROR gamma(-/-), and ROR alpha(sg/sg)ROR gamma(-/-) double knockout (DKO) mice by microarray analysis. DKO mice were generated to study functional redundancy between ROR alpha and ROR gamma. These analyses demonstrated that ROR alpha and ROR gamma affect the expression of a number of genes. ROR alpha and ROR gamma are particularly important in the regulation of genes encoding several phase I and phase II metabolic enzymes, including several 3beta-hydroxysteroid dehydrogenases, cytochrome P450 enzymes, and sulfotransferases. In addition, our results indicate that ROR alpha and ROR gamma each affect the expression of a specific set of genes but also exhibit functional redundancy. Our study shows that ROR alpha and ROR gamma receptors influence the regulation of several metabolic pathways, including those involved in the metabolism of steroids, bile acids, and xenobiotics, suggesting that RORs are important in the control of metabolic homeostasis.

  16. Progress of succinic acid production from renewable resources: Metabolic and fermentative strategies.

    Science.gov (United States)

    Jiang, Min; Ma, Jiangfeng; Wu, Mingke; Liu, Rongming; Liang, Liya; Xin, Fengxue; Zhang, Wenming; Jia, Honghua; Dong, Weiliang

    2017-12-01

    Succinic acid is a four-carbon dicarboxylic acid, which has attracted much interest due to its abroad usage as a precursor of many industrially important chemicals in the food, chemicals, and pharmaceutical industries. Facing the shortage of crude oil supply and demand of sustainable development, biological production of succinic acid from renewable resources has become a topic of worldwide interest. In recent decades, robust producing strain selection, metabolic engineering of model strains, and process optimization for succinic acid production have been developed. This review provides an overview of succinic acid producers and cultivation technology, highlight some of the successful metabolic engineering approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Comparative RNA-Sequence Transcriptome Analysis of Phenolic Acid Metabolism in Salvia miltiorrhiza, a Traditional Chinese Medicine Model Plant

    Directory of Open Access Journals (Sweden)

    Zhenqiao Song

    2017-01-01

    Full Text Available Salvia miltiorrhiza Bunge is an important traditional Chinese medicine (TCM. In this study, two S. miltiorrhiza genotypes (BH18 and ZH23 with different phenolic acid concentrations were used for de novo RNA sequencing (RNA-seq. A total of 170,787 transcripts and 56,216 unigenes were obtained. There were 670 differentially expressed genes (DEGs identified between BH18 and ZH23, 250 of which were upregulated in ZH23, with genes involved in the phenylpropanoid biosynthesis pathway being the most upregulated genes. Nine genes involved in the lignin biosynthesis pathway were upregulated in BH18 and thus result in higher lignin content in BH18. However, expression profiles of most genes involved in the core common upstream phenylpropanoid biosynthesis pathway were higher in ZH23 than that in BH18. These results indicated that genes involved in the core common upstream phenylpropanoid biosynthesis pathway might play an important role in downstream secondary metabolism and demonstrated that lignin biosynthesis was a putative partially competing pathway with phenolic acid biosynthesis. The results of this study expanded our understanding of the regulation of phenolic acid biosynthesis in S. miltiorrhiza.

  18. Low rates of lateral gene transfer among metabolic genes define the evolving biogeochemical niches of archaea through deep time.

    Science.gov (United States)

    Blank, Carrine E

    2012-01-01

    Phylogenomic analyses of archaeal genome sequences are providing windows into the group's evolutionary past, even though most archaeal taxa lack a conventional fossil record. Here, phylogenetic analyses were performed using key metabolic genes that define the metabolic niche of microorganisms. Such genes are generally considered to have undergone high rates of lateral gene transfer. Many gene sequences formed clades that were identical, or similar, to the tree constructed using large numbers of genes from the stable core of the genome. Surprisingly, such lateral transfer events were readily identified and quantifiable, occurring only a relatively small number of times in the archaeal domain of life. By placing gene acquisition events into a temporal framework, the rates by which new metabolic genes were acquired can be quantified. The highest lateral transfer rates were among cytochrome oxidase genes that use oxygen as a terminal electron acceptor (with a total of 12-14 lateral transfer events, or 3.4-4.0 events per billion years, across the entire archaeal domain). Genes involved in sulfur or nitrogen metabolism had much lower rates, on the order of one lateral transfer event per billion years. This suggests that lateral transfer rates of key metabolic proteins are rare and not rampant.

  19. Distribution and metabolism of ascorbic acid in pear fruits (Pyrus ...

    African Journals Online (AJOL)

    ajl user 1

    2013-04-17

    4048 ... Smirnoff-Wheeler pathway and uronic acid pathway whereas the flesh and core had lower capability for ascorbate synthesis. .... assay is based on the reduction of Fe3+ to Fe2+ by ascorbic acid in acidic solution.

  20. Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Derrick F. MacFabe

    2015-05-01

    Full Text Available Clinical observations suggest that gut and dietary factors transiently worsen and, in some cases, appear to improve behavioral symptoms in a subset of persons with autism spectrum disorders (ASDs, but the reason for this is unclear. Emerging evidence suggests ASDs are a family of systemic disorders of altered immunity, metabolism, and gene expression. Pre- or perinatal infection, hospitalization, or early antibiotic exposure, which may alter gut microbiota, have been suggested as potential risk factors for ASD. Can a common environmental agent link these disparate findings? This review outlines basic science and clinical evidence that enteric short-chain fatty acids (SCFAs, present in diet and also produced by opportunistic gut bacteria following fermentation of dietary carbohydrates, may be environmental triggers in ASD. Of note, propionic acid, a major SCFA produced by ASD-associated gastrointestinal bacteria (clostridia, bacteroides, desulfovibrio and also a common food preservative, can produce reversible behavioral, electrographic, neuroinflammatory, metabolic, and epigenetic changes closely resembling those found in ASD when administered to rodents. Major effects of these SCFAs may be through the alteration of mitochondrial function via the citric acid cycle and carnitine metabolism, or the epigenetic modulation of ASD-associated genes, which may be useful clinical biomarkers. It discusses the hypothesis that ASDs are produced by pre- or post-natal alterations in intestinal microbiota in sensitive sub-populations, which may have major implications in ASD cause, diagnosis, prevention, and treatment.

  1. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M

    2017-01-01

    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...... such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus...

  2. Uric acid, metabolic syndrome and atherosclerosis: the chicken or the egg, which comes first?

    Science.gov (United States)

    De Pergola, Giovanni; Cortese, Francesca; Termine, Gaetano; Meliota, Giovanni; Masiello, Michele; Cortese, Anna Maria; Silvestris, Francesco; Caccavo, Domenico; Ciccone, Marco Matteo

    2018-02-11

    A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease. to determine the relationship among serum uric acid and metabolic syndrome and atherosclerosis, by mean of carotid intima media-thickness, in a cohort of 811 otherwise healthy overweight/obese subjects, without overt atherosclerosis not using any kind of drug. Uric acid levels were positively related to male gender, waist circumference, BMI, systolic and diastolic pressure levels, fasting insulin, fasting glucose, HOMA-IR, triglycerides, total cholesterol, LDL cholesterol, the presence of metabolic syndrome and the number of the components of metabolic syndrome and negative related to HDL cholesterol levels. No correlation was found between uric acid and carotid intima media thickness. At the multiple regression analysis, only triglycerides (positively) and HDL-cholesterol (negatively) maintained an independent association with uric acid, while age, female gender and uric acid showed a significant independent association with metabolic syndrome. Moreover, the analysis of the odd ratios showed that the risk of developing metabolic syndrome was consistent with uric acid levels ranging from 3 mg/dl to 8 mg/dl. the presence of metabolic syndrome does not seem to provide hyperuricemia. By contrast, higher serum uric acid level may predict the risk of metabolic syndrome. Moreover, our results suggest that uric acid cannot be considered a risk factor for early atherosclerosis, at least when assessed using carotid ultrasound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. No association between type 1 diabetes and genetic variation in vitamin D metabolism genes

    DEFF Research Database (Denmark)

    Thorsen, Steffen U; Mortensen, Henrik B; Carstensen, Bendix

    2014-01-01

    BACKGROUND: Vitamin D, certain single nucleotide polymorphisms (SNPs) in the vitamin D-receptor (VDR) gene and vitamin D metabolism genes have been associated with type 1 diabetes (T1D). OBJECTIVE: We wanted to examine if the most widely studied SNPs in genes important for production, transport......). RESULTS: We did not demonstrate association with T1D for SNPs in the following genes: CYP27B1, VDR, GC, CYP2R1, DHCR7, and CYP24A1. Though, variants in the GC gene were significantly associated with 25(OH)D levels in the joint model. CONCLUSION: Some of the most examined SNPs in vitamin D metabolism genes...

  4. Genome-Scale Model of Streptococcus thermophilus LMG18311 for Metabolic Comparison of Lactic Acid Bacteria

    NARCIS (Netherlands)

    Pastink, M.I.; Teusink, B.; Hols, P.; Visser, S.; Vos, de W.M.; Hugenholtz, J.

    2009-01-01

    In this report we describe amino acid-metabolism and amino acid-dependency of the dairy bacterium Streptococcus thermophilus LMG18311 and compare that with two other characterized lactic acid bacteria, Lactococcus lactis and Lactobacillus plantarum. Through the construction of a genome-scale

  5. Phyletic distribution of fatty acid-binding protein genes.

    Directory of Open Access Journals (Sweden)

    Yadong Zheng

    Full Text Available Fatty acid-binding proteins (FABPs are a family of fatty acid-binding small proteins essential for lipid trafficking, energy storage and gene regulation. Although they have 20 to 70% amino acid sequence identity, these proteins share a conserved tertiary structure comprised of ten beta sheets and two alpha helixes. Availability of the complete genomes of 34 invertebrates, together with transcriptomes and ESTs, allowed us to systematically investigate the gene structure and alternative splicing of FABP genes over a wide range of phyla. Only in genomes of two cnidarian species could FABP genes not be identified. The genomic loci for FABP genes were diverse and their genomic structure varied. In particular, the intronless FABP genes, in most of which the key residues involved in fatty acid binding varied, were common in five phyla. Interestingly, several species including one trematode, one nematode and four arthropods generated FABP mRNA variants via alternative splicing. These results demonstrate that both gene duplication and post-transcriptional modifications are used to generate diverse FABPs in species studied.

  6. Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4

    Science.gov (United States)

    Arbones-Mainar, Jose M.; Johnson, Lance A.; Torres-Perez, Elena; Garcia, Anna E.; Perez-Diaz, Sergio; Raber, Jacob; Maeda, Nobuyo

    2016-01-01

    Background The Apolipoprotein E (APOE) gene encodes for three isoforms in the human population (APOE2, APOE3, and APOE4). While the role of APOE in lipid metabolism is well characterized, the specific metabolic signatures of the APOE isoforms, during metabolic disorders, remain unclear. Objective To elucidate the molecular underpinnings of APOE-directed metabolic alterations, we tested the hypothesis that APOE4 drives a whole-body metabolic shift toward increased lipid oxidation. Methods We employed humanized mice in which Apoe gene has been replaced by the human APOE*3 or APOE*4 allele to produce human APOE3 or APOE4 proteins and characterized several mechanisms of fatty acid oxidation, lipid storage, substrate utilization and thermogenesis in those mice. Results We show that while APOE4 mice gained less body weight and mass than their APOE3 counterparts on a Western-type diet (p<0.001), they displayed elevated insulin and HOMA, markers of insulin resistance (p=0.004 and p=0.025, respectively). APOE4 mice also demonstrated a reduced respiratory quotient during the postprandial period (0.95±0.03 vs. 1.06±0.03, p<0.001), indicating increased usage of lipids as opposed to carbohydrates as a fuel source. Finally, APOE4 mice showed increased body temperature (37.30 ± 0.68 vs 36.9 ± 0.58 °C, p=0.039), augmented cold tolerance, and more metabolically active brown adipose tissue compared to APOE3 mice. Conclusion These data suggest that APOE4 mice may resist weight gain via an APOE4-directed global metabolic shift toward lipid oxidation and enhanced thermogenesis, and may represent a critical first step in the development of APOE-directed therapies for a large percentage of the population affected by disorders with established links to APOE and metabolism. PMID:27163745

  7. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Hornstra, G.; de Koning, T. J.; Smeitink, J. A. M.; Bakker, H. D.; de Klerk, H. B. C.; Rubio-Gozalbo, M. E.

    2006-01-01

    Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because

  8. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Hornstra, G.; Koning, T.J.; Smeitink, J.A.M.; Bakker, H.D.; Klerk, H. de; Rubio-Gozalbo, M.E.

    2006-01-01

    Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because

  9. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism

    NARCIS (Netherlands)

    Vlaardingerbroek, H; Hornstra, G; de Koning, T J; Smeitink, J A M; Bakker, H D; de Klerk, H B C; Rubio-Gozalbo, M E

    Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because

  10. Daily rhythms in expression of genes of hepatic lipid metabolism in Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Betancor, Mónica B; McStay, Elsbeth; Minghetti, Matteo; Migaud, Hervé; Tocher, Douglas R; Davie, Andrew

    2014-01-01

    In mammals, several genes involved in liver lipid and cholesterol homeostasis are rhythmically expressed with expression shown to be regulated by clock genes via Rev-erb 1α. In order to elucidate clock gene regulation of genes involved in lipid metabolism in Atlantic salmon (Salmo salar L.), the orphan nuclear receptor Rev-erb 1α was cloned and 24 h expression of clock genes, transcription factors and genes involved in cholesterol and lipid metabolism determined in liver of parr acclimated to a long-day photoperiod, which was previously shown to elicit rhythmic clock gene expression in the brain. Of the 31 genes analysed, significant daily expression was demonstrated in the clock gene Bmal1, transcription factor genes Srebp1, Lxr, Pparα and Pparγ, and several lipid metabolism genes Hmgcr, Ipi, ApoCII and El. The possible regulatory mechanisms and pathways, and the functional significance of these patterns of expression were discussed. Importantly and in contrast to mammals, Per1, Per2, Fas, Srebp2, Cyp71α and Rev-erb 1α did not display significant daily rhythmicity in salmon. The present study is the first report characterising 24 h profiles of gene expression in liver of Atlantic salmon. However, more importantly, the predominant role of lipids in the nutrition and metabolism of fish, and of feed efficiency in determining farming economics, means that daily rhythmicity in the regulation of lipid metabolism will be an area of considerable interest for future research in commercially important species.

  11. Effect of multiple mutations in tricarboxylic acid cycle and one-carbon metabolism pathways on Edwardsiella ictaluri pathogenesis.

    Science.gov (United States)

    Dahal, N; Abdelhamed, H; Lu, J; Karsi, A; Lawrence, M L

    2014-02-21

    Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of catfish (ESC). We have shown recently that tricarboxylic acid cycle (TCA) and one-carbon (C1) metabolism are involved in E. ictaluri pathogenesis. However, the effect of multiple mutations in these pathways is unknown. Here, we report four novel E. ictaluri mutants carrying double gene mutations in TCA cycle (EiΔmdhΔsdhC, EiΔfrdAΔsdhC), C1 metabolism (EiΔglyAΔgcvP), and both TCA and C1 metabolism pathways (EiΔgcvPΔsdhC). In-frame gene deletions were constructed by allelic exchange and mutants' virulence and vaccine efficacy were evaluated using in vivo bioluminescence imaging (BLI) as well as end point mortality counts in catfish fingerlings. Results indicated that all the double gene mutants were attenuated compared to wild-type (wt) E. ictaluri. There was a 1.39-fold average reduction in bioluminescence, and hence bacterial numbers, from all the mutants except for EiΔfrdAΔsdhC at 144 h post-infection. Vaccination with mutants was very effective in protecting channel catfish against subsequent infection with virulent E. ictaluri 93-146 strain. In particular, immersion vaccination resulted in complete protection. Our results provide further evidence on the importance of TCA and C1 metabolism pathways in bacterial pathogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. The transferome of metabolic genes explored: analysis of the horizontal transfer of enzyme encoding genes in unicellular eukaryotes.

    Science.gov (United States)

    Whitaker, John W; McConkey, Glenn A; Westhead, David R

    2009-01-01

    Metabolic networks are responsible for many essential cellular processes, and exhibit a high level of evolutionary conservation from bacteria to eukaryotes. If genes encoding metabolic enzymes are horizontally transferred and are advantageous, they are likely to become fixed. Horizontal gene transfer (HGT) has played a key role in prokaryotic evolution and its importance in eukaryotes is increasingly evident. High levels of endosymbiotic gene transfer (EGT) accompanied the establishment of plastids and mitochondria, and more recent events have allowed further acquisition of bacterial genes. Here, we present the first comprehensive multi-species analysis of E/HGT of genes encoding metabolic enzymes from bacteria to unicellular eukaryotes. The phylogenetic trees of 2,257 metabolic enzymes were used to make E/HGT assertions in ten groups of unicellular eukaryotes, revealing the sources and metabolic processes of the transferred genes. Analyses revealed a preference for enzymes encoded by genes gained through horizontal and endosymbiotic transfers to be connected in the metabolic network. Enrichment in particular functional classes was particularly revealing: alongside plastid related processes and carbohydrate metabolism, this highlighted a number of pathways in eukaryotic parasites that are rich in enzymes encoded by transferred genes, and potentially key to pathogenicity. The plant parasites Phytophthora were discovered to have a potential pathway for lipopolysaccharide biosynthesis of E/HGT origin not seen before in eukaryotes outside the Plantae. The number of enzymes encoded by genes gained through E/HGT has been established, providing insight into functional gain during the evolution of unicellular eukaryotes. In eukaryotic parasites, genes encoding enzymes that have been gained through horizontal transfer may be attractive drug targets if they are part of processes not present in the host, or are significantly diverged from equivalent host enzymes.

  13. Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites

    Science.gov (United States)

    Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi

    2011-01-01

    Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a “one pot” suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using 13C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems. PMID:21825143

  14. The metabolic regulator CodY links L. monocytogenes metabolism to virulence by directly activating the virulence regulatory gene, prfA

    Science.gov (United States)

    Lobel, Lior; Sigal, Nadejda; Borovok, Ilya; Belitsky, Boris R.; Sonenshein, Abraham L.; Herskovits, Anat A.

    2015-01-01

    Summary Metabolic adaptations are critical to the ability of bacterial pathogens to grow within host cells and are normally preceded by sensing of host-specific metabolic signals, which in turn can influence the pathogen's virulence state. Previously, we reported that the intracellular bacterial pathogen Listeria monocytogenes responds to low availability of branched-chain amino acids (BCAA) within mammalian cells by up-regulating both BCAA biosynthesis and virulence genes. The induction of virulence genes required the BCAA-responsive transcription regulator, CodY, but the molecular mechanism governing this mode of regulation was unclear. In this report, we demonstrate that CodY directly binds the coding sequence of the L. monocytogenes master virulence activator gene, prfA, 15 nt downstream of its start codon, and that this binding results in up-regulation of prfA transcription specifically under low concentrations of BCAA. Mutating this site abolished CodY binding and reduced prfA transcription in macrophages, and attenuated bacterial virulence in mice. Notably, the mutated binding site did not alter prfA transcription or PrfA activity under other conditions that are known to activate PrfA, such as during growth in the presence of glucose-1-phosphate. This study highlights the tight crosstalk between L. monocytogenes metabolism and virulence' while revealing novel features of CodY-mediated regulation. PMID:25430920

  15. Transcriptomic Analysis Reveals the Metabolic Mechanism of L-Ascorbic Acid in Ziziphus jujuba Mill.

    Science.gov (United States)

    Zhang, Chunmei; Huang, Jian; Li, Xingang

    2016-01-01

    Chinese jujube (Ziziphus jujuba Mill.) is the most economically important member of the Rhamnaceae family and contains a high concentration of ascorbic acid (AsA). To explore the metabolic mechanism of AsA accumulation, we investigated the abundance of AsA in the fruit development stages, the leaf and flower of Z. jujuba cv Junzao, and the mature fruit of one type of wild jujube (Z. jujuba var. spinosa Hu, Yanchuan sour jujube). And the expression patterns of genes involved in AsA biosynthesis, degradation, and recycling were analyzed. The result showed that AsA biosynthesis during early fruit development (the enlargement stage) is the main reason for jujube high accumulation. The L-galactose pathway plays a predominant role in the biosynthesis of AsA during jujube fruit development, and the genes GMP1, GME1, GGP, and GaLDH involved in the determination of AsA concentration during fruit development and in different genotypes; the myo-inositol pathway along with the genes GME2 and GMP2 in the L-galactose pathway play a compensatory role in maintaining AsA accumulation during the ripening stage. These findings enhance our understanding of the molecular mechanism in regulating AsA accumulation for jujube. PMID:26913041

  16. Transcriptomic analysis reveals the metabolic mechanism of L-ascorbic acid in Ziziphus jujuba Mill.

    Directory of Open Access Journals (Sweden)

    Chunmei eZhang

    2016-02-01

    Full Text Available Chinese jujube (Ziziphus jujuba Mill. is the most economically important member of the Rhamnaceae family and contains a high concentration of ascorbic acid (AsA. To explore the metabolic mechanism of AsA accumulation, we investigated the abundance of AsA in the fruit development stages, the leaf and flower of Z. jujuba cv Junzao, and the mature fruit of one type of wild jujube (Z. jujuba var. spinosa Hu, Yanchuan sour jujube. And the expression patterns of genes involved in AsA biosynthesis, degradation and recycling were analyzed. The result showed that AsA biosynthesis during early fruit development (the enlargement stage is the main reason for jujube high accumulation. The L-galactose pathway plays a predominant role in the biosynthesis of AsA during jujube fruit development, and the genes GMP1, GME1, GGP, and GaLDH involved in the determination of AsA concentration during fruit development and in different genotypes; the myo-inositol pathway along with the genes GME2 and GMP2 in the L-galactose pathway play a compensatory role in maintaining AsA accumulation during the ripening stage. These findings enhance our understanding of the molecular mechanism in regulating AsA accumulation for jujube.

  17. Megaloblastic anaemia: Folic acid and vitamin B12 metabolism

    National Research Council Canada - National Science Library

    H.B. Castellanos-Sinco; C.O. Ramos-Peñafiel; A. Santoyo-Sánchez; J. Collazo-Jaloma; C. Martínez-Murillo; E. Montaño-Figueroa; A. Sinco-Ángeles

    2015-01-01

    .... An understanding of the metabolism of these vitamins will enable clinicians to make the best use and interpretation of laboratory studies and monitor therapeutic strategies, which consist mainly...

  18. Effect of Dietary Fatty Acids on Human Lipoprotein Metabolism: A Comprehensive Update

    Directory of Open Access Journals (Sweden)

    Esther M.M. Ooi

    2015-06-01

    Full Text Available Dyslipidemia is a major risk factor for cardiovascular disease (CVD. Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA consumption diminished hepatic triglyceride-rich lipoprotein (TRL secretion and enhanced TRL to low-density lipoprotein (LDL conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids.

  19. Fish oil and the pan-PPAR agonist tetradecylthioacetic acid affect the amino acid and carnitine metabolism in rats.

    Science.gov (United States)

    Bjørndal, Bodil; Brattelid, Trond; Strand, Elin; Vigerust, Natalya Filipchuk; Svingen, Gard Frodahl Tveitevåg; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf Kristian

    2013-01-01

    Peroxisome proliferator-activated receptors (PPARs) are important in the regulation of lipid and glucose metabolism. Recent studies have shown that PPARα-activation by WY 14,643 regulates the metabolism of amino acids. We investigated the effect of PPAR activation on plasma amino acid levels using two PPARα activators with different ligand binding properties, tetradecylthioacetic acid (TTA) and fish oil, where the pan-PPAR agonist TTA is a more potent ligand than omega-3 polyunsaturated fatty acids. In addition, plasma L-carnitine esters were investigated to reflect cellular fatty acid catabolism. Male Wistar rats (Rattus norvegicus) were fed a high-fat (25% w/w) diet including TTA (0.375%, w/w), fish oil (10%, w/w) or a combination of both. The rats were fed for 50 weeks, and although TTA and fish oil had hypotriglyceridemic effects in these animals, only TTA lowered the body weight gain compared to high fat control animals. Distinct dietary effects of fish oil and TTA were observed on plasma amino acid composition. Administration of TTA led to increased plasma levels of the majority of amino acids, except arginine and lysine, which were reduced. Fish oil however, increased plasma levels of only a few amino acids, and the combination showed an intermediate or TTA-dominated effect. On the other hand, TTA and fish oil additively reduced plasma levels of the L-carnitine precursor γ-butyrobetaine, as well as the carnitine esters acetylcarnitine, propionylcarnitine, valeryl/isovalerylcarnitine, and octanoylcarnitine. These data suggest that while both fish oil and TTA affect lipid metabolism, strong PPARα activation is required to obtain effects on amino acid plasma levels. TTA and fish oil may influence amino acid metabolism through different metabolic mechanisms.

  20. The impact of nutrients on clock genes and metabolism: their role for the prevention and treatment of metabolic diseases

    OpenAIRE

    Castillo Figueroa, Ana Lucía

    2017-01-01

    [eng] A number of recent studies in animals and humans have linked energy regulation and the circadian clock at the molecular, physiological and behavioral levels, concluding that disruption of clock genes results in metabolic dysregulation. Obesity and type 2 diabetes are associated with disruption of circadian rhythms. Strategies to prevent disturbances in circadian rhythms are critical in order to find potential targets for new therapies development and treatment for metabolic diseases. ...

  1. The impact of nutrients on clock genes and metabolism: their role for the prevention and treatment of metabolic diseases

    OpenAIRE

    Castillo Figueroa, Ana Lucía

    2017-01-01

    A number of recent studies in animals and humans have linked energy regulation and the circadian clock at the molecular, physiological and behavioral levels, concluding that disruption of clock genes results in metabolic dysregulation. Obesity and type 2 diabetes are associated with disruption of circadian rhythms. Strategies to prevent disturbances in circadian rhythms are critical in order to find potential targets for new therapies development and treatment for metabolic diseases. Potentia...

  2. Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver

    Directory of Open Access Journals (Sweden)

    Lai Peng

    2016-09-01

    Full Text Available The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation. Farnesoid X receptor (FXR is critical for bile acid and lipid homeostasis in liver. However, the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear. Hence, we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control (C57BL/6 mouse livers during development. Liver samples of male C57BL/6 and Fxr-null mice at 6 different ages from prenatal to adult were used. The Fxr-null showed an overall effect to diminish the “day-1 surge” of phase-I gene expression, including cytochrome P450s at neonatal ages. Among the 185 phase-I genes from 12 different families, 136 were expressed, and differential expression during development occurred in genes from all 12 phase-I families, including hydrolysis: carboxylesterase (Ces, paraoxonase (Pon, and epoxide hydrolase (Ephx; reduction: aldoketo reductase (Akr, quinone oxidoreductase (Nqo, and dihydropyrimidine dehydrogenase (Dpyd; and oxidation: alcohol dehydrogenase (Adh, aldehyde dehydrogenase (Aldh, flavin monooxygenases (Fmo, molybdenum hydroxylase (Aox and Xdh, cytochrome P450 (P450, and cytochrome P450 oxidoreductase (Por. The data also suggested new phase-I genes potentially targeted by FXR. These results revealed an important role of FXR in regulation of ontogeny of phase-I genes.

  3. Branched chain amino acids requirements and metabolism in pigs

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham

    2015-01-01

    by increasing SID Leu:Lys in the diet were plasma Phe, α-ketoisovaleric acid, creatine, Ile, 3-methyl-oxovaleric acid, Trp and urinary Ile, glutamate, choline, cytosine, 3-hydroxy-2-methyl-[S-(R,R)]-butanoic acid, acetyl-DL-valine, L-2-aminoadipic acid, 2-methylbutyrylglycine, Tyr, and L-ascorbic acid. Among...... the identified metabolites, those that could be linked to the animal growth performance were plasma glycocholic acid and taurocholic acid which were concluded as biomarkers of the optimum dietary Ile level. Plasma creatine, urinary 2-aminoadipic acid, ascorbic acid, and choline were identified as biomarkers......There is an interest to reduce the dietary crude protein (CP) level to promote the gut health of piglets, eliminate the environmental nitrogen load from intensive pig farming, and to reduce diet costs. This is possible by estimating individual amino acid (AA) requirements and by optimizing the diet...

  4. Mathematical modelling of microbes: metabolism, gene expression and growth

    Science.gov (United States)

    Cinquemani, Eugenio; Ropers, Delphine; Gouzé, Jean-Luc

    2017-01-01

    The growth of microorganisms involves the conversion of nutrients in the environment into biomass, mostly proteins and other macromolecules. This conversion is accomplished by networks of biochemical reactions cutting across cellular functions, such as metabolism, gene expression, transport and signalling. Mathematical modelling is a powerful tool for gaining an understanding of the functioning of this large and complex system and the role played by individual constituents and mechanisms. This requires models of microbial growth that provide an integrated view of the reaction networks and bridge the scale from individual reactions to the growth of a population. In this review, we derive a general framework for the kinetic modelling of microbial growth from basic hypotheses about the underlying reaction systems. Moreover, we show that several families of approximate models presented in the literature, notably flux balance models and coarse-grained whole-cell models, can be derived with the help of additional simplifying hypotheses. This perspective clearly brings out how apparently quite different modelling approaches are related on a deeper level, and suggests directions for further research. PMID:29187637

  5. [Percentage of uric acid calculus and its metabolic character in Dongjiang River valley].

    Science.gov (United States)

    Chong, Hong-Heng; An, Geng

    2009-02-15

    To study the percentage of uric acid calculus in uroliths and its metabolic character in Dongjiang River valley. To analyze the chemical composition of 290 urinary stones by infrared (IR) spectroscopy and study the ratio changes of uric acid calculus. Uric acid calculus patients and healthy people were studied. Personal characteristics, dietary habits were collected. Conditional logistic regression was used for data analysis and studied the dietary risk factors of uric acid calculus. Patients with uric acid calculus, calcium oxalate and those without urinary calculus were undergone metabolic evaluation analysis. The results of uric acid calculus patients compared to another two groups to analysis the relations between the formation of uric acid calculus and metabolism factors. Uric acid calculi were found in 53 cases (18.3%). The multiple logistic regression analysis suggested that low daily water intake, eating more salted and animal food, less vegetable were very closely associated with uric acid calculus. Comparing to calcium oxalate patients, the urine volume, the value of pH, urine calcium, urine oxalic acid were lower, but uric acid was higher than it. The value of pH, urine oxalic acid and citric acid were lower than them, but uric acid and urine calcium were higher than none urinary calculus peoples. Blood potassium and magnesium were lower than them. The percentage of uric acid stones had obvious advanced. Less daily water intake, eating salted food, eating more animal food, less vegetables and daily orange juice intake, eating sea food are the mainly dietary risk factors to the formation of uric acid calculus. Urine volume, the value of pH, citric acid, urine calcium, urine uric acid and the blood natrium, potassium, magnesium, calcium, uric acid have significant influence to the information of uric acid stones.

  6. Increased isobutanol production in Saccharomyces cerevisiae by overexpression of genes in valine metabolism

    DEFF Research Database (Denmark)

    Chen, Xiao; Nielsen, Kristian Fog; Borodina, Irina

    2011-01-01

    BACKGROUND: Isobutanol can be a better biofuel than ethanol due to its higher energy density and lower hygroscopicity. Furthermore, the branched-chain structure of isobutanol gives a higher octane number than the isomeric n-butanol. Saccharomyces cerevisiae was chosen as the production host because...... overexpression of biosynthetic genes ILV2, ILV3, and ILV5 in valine metabolism in anaerobic fermentation of glucose in mineral medium in S. cerevisiae. Isobutanol yield was further improved by twofold by the additional overexpression of BAT2, encoding the cytoplasmic branched-chain amino-acid aminotransferase....... Overexpression of ILV6, encoding the regulatory subunit of Ilv2, in the ILV2 ILV3 ILV5 overexpression strain decreased isobutanol production yield by threefold. In aerobic cultivations in shake flasks in mineral medium, the isobutanol yield of the ILV2 ILV3 ILV5 overexpression strain and the reference strain...

  7. Peptide and amino acid metabolism is controlled by an OmpR-family response regulator in Lactobacillus casei.

    Science.gov (United States)

    Alcántara, Cristina; Bäuerl, Christine; Revilla-Guarinos, Ainhoa; Pérez-Martínez, Gaspar; Monedero, Vicente; Zúñiga, Manuel

    2016-04-01

    A Lactobacillus casei BL23 strain defective in an OmpR-family response regulator encoded by LCABL_18980 (PrcR, RR11), showed enhanced proteolytic activity caused by overexpression of the gene encoding the proteinase PrtP. Transcriptomic analysis revealed that, in addition to prtP expression, PrcR regulates genes encoding peptide and amino acid transporters, intracellular peptidases and amino acid biosynthetic pathways, among others. Binding of PrcR to twelve promoter regions of both upregulated and downregulated genes, including its own promoter, was demonstrated by electrophoretic mobility shift assays showing that PrcR can act as a transcriptional repressor or activator. Phosphorylation of PrcR increased its DNA binding activity and this effect was abolished after replacement of the phosphorylatable residue Asp-52 by alanine. Comparison of the transcript levels in cells grown in the presence or absence of tryptone in the growth medium revealed that PrcR activity responded to the presence of a complex amino acid source in the growth medium. We conclude that the PrcR plays a major role in the control of the peptide and amino acid metabolism in L. casei BL23. Orthologous prcR genes are present in most members of the Lactobacillaceae and Leuconostocaceae families. We hypothesize that they play a similar role in these bacterial groups. © 2015 John Wiley & Sons Ltd.

  8. Transcriptome and Gene Ontology (GO) Enrichment Analysis Reveals Genes Involved in Biotin Metabolism That Affect L-Lysine Production in Corynebacterium glutamicum.

    Science.gov (United States)

    Kim, Hong-Il; Kim, Jong-Hyeon; Park, Young-Jin

    2016-03-09

    Corynebacterium glutamicum is widely used for amino acid production. In the present study, 543 genes showed a significant change in their mRNA expression levels in L-lysine-producing C. glutamicum ATCC21300 than that in the wild-type C. glutamicum ATCC13032. Among these 543 differentially expressed genes (DEGs), 28 genes were up- or downregulated. In addition, 454 DEGs were functionally enriched and categorized based on BLAST sequence homologies and gene ontology (GO) annotations using the Blast2GO software. Interestingly, NCgl0071 (bioB, encoding biotin synthase) was expressed at levels ~20-fold higher in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain. Five other genes involved in biotin metabolism or transport--NCgl2515 (bioA, encoding adenosylmethionine-8-amino-7-oxononanoate aminotransferase), NCgl2516 (bioD, encoding dithiobiotin synthetase), NCgl1883, NCgl1884, and NCgl1885--were also expressed at significantly higher levels in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain, which we determined using both next-generation RNA sequencing and quantitative real-time PCR analysis. When we disrupted the bioB gene in C. glutamicum ATCC21300, L-lysine production decreased by approximately 76%, and the three genes involved in biotin transport (NCgl1883, NCgl1884, and NCgl1885) were significantly downregulated. These results will be helpful to improve our understanding of C. glutamicum for industrial amino acid production.

  9. ELOVL6 Genetic Variation Is Related to Insulin Sensitivity: A New Candidate Gene in Energy Metabolism

    Science.gov (United States)

    Morcillo, Sonsoles; Martín-Núñez, Gracia María; Rojo-Martínez, Gemma; Almaraz, María Cruz; García-Escobar, Eva; Mansego, María Luisa; de Marco, Griselda; Chaves, Felipe J.; Soriguer, Federico

    2011-01-01

    Background The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1). Objective We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain. Design We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex. Results Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001). Conclusions Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study. PMID:21701577

  10. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

    Science.gov (United States)

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas D E; Rozen, Rima

    2015-03-01

    Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Folic acid-supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr(+/+) and Mthfr(+/-) mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr(+/-) mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr(+/-) livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr(+/-) mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot

  11. Gene expression patterns of invertase gene families and modulation of the inhibitor gene in tomato sucrose metabolism.

    Science.gov (United States)

    Zhang, Y L; Zhang, A H; Jiang, J

    2013-01-24

    Patterns of gene expression in the different types of sucrose metabolism in the tomato are highly variable and heritable. This genetic variation causes considerable functional differences. We examined the patterns of expression of invertase (Inv) gene families and an invertase inhibitor (INH) gene involved in elongating roots, hypocotyls, and fruit of the tomato (Lycopersicon esculentum cv. Micro-Tom and L. chmielewskii) through a real-time quantitative PCR analysis. We found that the Lin6 gene plays an important role in the vegetative growth stage. Lin5 and Lin7 did not express in Micro-Tom, but did express in L. chmielewskii. Overall relative expression levels of sucrose Inv gene families were significantly lower in L. chmielewskii during the reproductive growth stage than in Micro-Tom, being up to hundreds of times lower. It was not expressed in the dissepiment in L. chmielewskii. We suggest that differences in sucrose accumulation in tomato fruit is mainly due to differentially expressed invertase gene families at the later fruit growth stages.

  12. Inverse metabolic engineering based on transient acclimation of yeast improves acid-containing xylose fermentation and tolerance to formic and acetic acids.

    Science.gov (United States)

    Hasunuma, Tomohisa; Sakamoto, Takatoshi; Kondo, Akihiko

    2016-01-01

    Improving the production of ethanol from xylose is an important goal in metabolic engineering of Saccharomyces cerevisiae. Furthermore, S. cerevisiae must produce ethanol in the presence of weak acids (formate and acetate) generated during pre-treatment of lignocellulosic biomass. In this study, weak acid-containing xylose fermentation was significantly improved using cells that were acclimated to the weak acids during pre-cultivation. Transcriptome analyses showed that levels of transcripts for transcriptional/translational machinery-related genes (RTC3 and ANB1) were enhanced by formate and acetate acclimation. Recombinant yeast strains overexpressing RTC3 and ANB1 demonstrated improved ethanol production from xylose in the presence of the weak acids, along with improved tolerance to the acids. Novel metabolic engineering strategy based on the combination of short-term acclimation and system-wide analysis was developed, which can develop stress-tolerant strains in a short period of time, although conventional evolutionary engineering approach has required long periods of time to isolate inhibitor-adapted strains.

  13. Gene expression of regulatory enzymes involved in the intermediate metabolism of sheep subjected to feed restriction.

    Science.gov (United States)

    van Harten, S; Brito, R; Almeida, A M; Scanlon, T; Kilminster, T; Milton, J; Greeff, J; Oldham, C; Cardoso, L A

    2013-03-01

    The effect of feed restriction on gene expression of regulatory enzymes of intermediary metabolism was studied in two sheep breeds (Australian Merino and Dorper) subjected to two nutritional treatments: feed restriction (85% of daily maintenance requirements) and control (ad libitum feeding), during 42 days. The experimental animals (ram lambs) were divided into four groups, n = 5 (Australian Merino control (MC), Australian Merino Restriction (MR), Dorper control (DC) and Dorper Restriction (DR)). After the trial, animals were sacrificed and samples were taken from liver tissue to quantify glucose levels and gene expression of relevant intermediary metabolism enzymes (phosphofructokinase (PFK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, glucose-6-phosphatase, glycogen synthase (GS), fatty acid synthase (FAS), glutamate dehydrogenase (GDH) and carbamoyl phosphate synthase (CPS)) through real-time PCR. During the experimental period, the MR animals lost 12.6% in BW compared with 5.3% lost by the Dorper lambs. MC and DC rams gained, respectively, 8.8% and 14% during the same period. Within the Dorper breed, restricted feed animals revealed a significant decrease over controls in the transcription of PFK (1.95-fold) and PK (2.26-fold), both glycolytic enzymes. The gluconeogenesis showed no change in the feed restricted animals of both breeds. DR feed group presented a significant decrease over the homologous Merino sheep group on GS. In both experimental breeds, FAS mRNA expression was decreased in restricted feed groups. GDH expression was decreased only in the DR animals (1.84-fold) indicating a reduced catabolism of amino acids in these animals. Finally, CPS was significantly (P enzymes and hepatic glucose production of Dorper sheep to feed restriction concurring with the BW results in the experimental groups.

  14. Diet-gene interactions between dietary fat intake and common polymorphisms in determining lipid metabolism

    Directory of Open Access Journals (Sweden)

    Corella, Dolores

    2009-03-01

    Full Text Available Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolim-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 514C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C metabolism; the interaction between polyunsaturated fatty acids (PUFA and the 75G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the 1131TC in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken.Las recomendaciones dietéticas actuales referentes al consumo de grasas en la dieta han sido realizadas sin tener en cuenta las posibles diferencias genéticas de las personas que podrían ser las responsables de las diferentes respuestas interindividuales que frecuentemente se observan ante la misma dieta. La presencia de variabilidad genética ha sido puesta de manifiesto para todos los genes relacionados con el metabolismo lipídico, por lo que existe un ingente número de genes y de variantes genéticas para ser incluidas en los estudios sobre interacciones dieta-genotipo en el ámbito específico del consumo de grasas y aceites. Se revisarán algunos ejemplos sobre interacciones grasa

  15. Tissue-based metabolic labeling of polysialic acids in living primary hippocampal neurons

    National Research Council Canada - National Science Library

    Kyungtae Kang; Sunghoon Joo; Ji Yu Choi; Sujeong Geum; Seok-Pyo Hong; Seung-Yeul Lee; Yong Ho Kim; Seong-Min Kim; Myung-Han Yoon; Yoonkey Nam; Kyung-Bok Lee; Hee-Yoon Lee; Insung S. Choi

    2015-01-01

    ... to present N-azidoacetyl sialic acid to PSA-NCAM. Although significant neurotoxicity was observed in the conventional metabolic labeling that used the dissociated neuron cells, neurotoxicity disappeared in this modified strategy, allowing...

  16. Metabolic engineering of Ustilago trichophora TZ1 for improved malic acid production

    Directory of Open Access Journals (Sweden)

    Thiemo Zambanini

    2017-06-01

    These results open up a wide range of possibilities for further optimization, especially combinatorial metabolic engineering to increase the flux from pyruvate to malic acid and to reduce by-product formation.

  17. 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.

  18. How to Do It. Plant Eco-Physiology: Experiments on Crassulacean Acid Metabolism, Using Minimal Equipment.

    Science.gov (United States)

    Friend, Douglas J. C.

    1990-01-01

    Features of Crassulacean Acid Metabolism plants are presented. Investigations of a complex eco-physiological plant adaptation to the problems of growth in an arid environment are discussed. Materials and procedures for these investigations are described. (CW)

  19. Metabolic Syndrome, Alcohol Consumption and Genetic Factors Are Associated with Serum Uric Acid Concentration

    OpenAIRE

    Stibůrková, Blanka; Pavlíková, Markéta; Sokolová, Jitka; Kožich, Viktor

    2014-01-01

    Objective Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. Methods The cohort consisted of 589 healthy subjects aged 18–65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and ...

  20. Dietary fatty acids affecting hepatic metabolism and atherosclerosis - mechanisms unravelled using a proteomics approach

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Gutierrez, G.; Roos, B. de

    2009-07-01

    Dietary fatty acids play an important role in the aetiology of coronary heart disease. The effects of dietary fatty acids on lipoprotein metabolism are well described, but additional or alternative mechanisms relating to potential influence on coronary heart disease are not known. This review describes how proteomics techniques have been used to identify proteins that are differentially regulated by dietary fatty acids. Such proteins may reveal pathways by which dietary fatty acids influence disease risk. (Author) 40 refs.

  1. Plasma fatty acids and the risk of metabolic syndrome in ethnic Chinese adults in Taiwan

    Directory of Open Access Journals (Sweden)

    Hsu Hsiu-Ching

    2011-02-01

    Full Text Available Abstract Background Evidence of predictive power of various fatty acids on the risk of metabolic syndrome was scanty. We evaluated the role of various fatty acids, including saturated fat, monounsaturated fat, transfat, n-6 fatty acid, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, for the risk of the metabolic syndrome in Taiwan. Results A nested case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control subjects. For saturated fat, monounsaturated fat and transfat, the higher the concentration the higher the risk for metabolic syndrome: participants in the highest quintile had a 2.22-fold (95% confidence interval [CI], 1.66 to 2.97 higher risk of metabolic syndrome. In addition, the participants in higher EPA quintiles were less likely to have the risk of metabolic syndrome (adjusted risk, 0.46 [0.34 to 0.61] for the fifth quintile. Participants in the highest risk group (low EPA and high transfat had a 2.36-fold higher risk of metabolic syndrome (95% CI, 1.38 to 4.03, compared with those in the lowest risk group (high EPA and low transfat. For prediction power, the area under ROC curves increased from 0.926 in the baseline model to 0.928 after adding fatty acids. The net reclassification improvement for metabolic syndrome risk was substantial for saturated fat (2.1%, P = 0.05. Conclusions Plasma fatty acid components improved the prediction of the metabolic syndrome risk in Taiwan.

  2. Analysis of miRNAs and their target genes associated with lipid metabolism in duck liver.

    Science.gov (United States)

    He, Jun; Wang, Weiqun; Lu, Lizhi; Tian, Yong; Niu, Dong; Ren, Jindong; Dong, Liyan; Sun, Siwei; Zhao, Yan; Chen, Li; Shen, Jianliang; Li, Xiuhong

    2016-06-08

    Fat character is an important index in duck culture that linked to local flavor, feed cost and fat intake for costumers. Since the regulation networks in duck lipid metabolism had not been reported very clearly, we aimed to explore the potential miRNA-mRNA pairs and their regulatory roles in duck lipid metabolism. Here, Cherry-Valley ducks were selected and treated with/without 5% oil added in feed for 2 weeks, and then fat content determination was performed on. The data showed that the fat contents and the fatty acid ratios of C17:1 and C18:2 were up-regulated in livers of oil-added ducks, while the C12:0 ratio was down-regulated. Then 21 differential miRNAs, including 10 novel miRNAs, were obtain from the livers by sequencing, and 73 target genes involved in lipid metabolic processes of these miRNAs were found, which constituted 316 miRNA-mRNA pairs. Two miRNA-mRNA pairs including one novel miRNA and one known miRNA, N-miR-1