16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium.

Science.gov (United States)

Lee, Byung Chul; Kim, Dong Hyun; Lee, Iljung; Choe, Yearn Seong; Chi, Dae Yoon; Lee, Kyung-Han; Choi, Yong; Kim, Byung-Tae

2008-06-26

We synthesized 16-cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid (99mTc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.3% decay-corrected yield by a double ligand transfer reaction between the ferrocene adduct of methyl hexadecanoate ( 2) and Na99mTcO 4 in the presence of Cr(CO)6 and CrCl3, followed by hydrolysis of the methyl ester group. Radiotracer 1 was found to be chemically stable (99% at 6 h) when incubated in human serum. A tissue distribution study in mice showed that high radioactivity accumulated in heart (9.03%ID/g at 1 min and 5.41%ID/g at 5 min postinjection) with rapid clearance and that heart to blood uptake ratios increased with time (2.13 at 5 min and 3.76 at 30 min postinjection). Metabolite analysis of the heart tissues using a simple extraction method showed that 99mTc-CpTT-4-oxo-butyric acid was detected as the major radioactive metabolite by HPLC, suggesting that 1 is metabolized to 99mTc-CpTT-4-oxo-butyric acid via beta-oxidation in myocardium.

The Recently Identified Isoleucine Conjugate of cis-12-Oxo-Phytodienoic Acid Is Partially Active in cis-12-Oxo-Phytodienoic Acid-Specific Gene Expression of Arabidopsis thaliana

Czech Academy of Sciences Publication Activity Database

Arnold, M.D.; Gruber, C.; Floková, Kristýna; Miersch, Otto; Strnad, Miroslav; Novák, Ondřej; Wasternack, Claus; Hause, B.

2016-01-01

Roč. 11, č. 9 (2016), e0162829 E-ISSN 1932-6203 R&D Projects: GA ČR GA14-34792S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ALLENE-OXIDE-CYCLASE * 12-OXO-PHYTODIENOIC ACID * JASMONIC ACID Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines.

Science.gov (United States)

Bjedov, Srđan; Jakimov, Dimitar; Pilipović, Ana; Poša, Mihalj; Sakač, Marija

2017-04-01

Bile acid derivatives with modifications in side chain and modifications on steroid skeleton were synthetized and their antitumor activity against five human cancer cell lines was investigated. Modifications in side chain include amid group, formed in reaction with 2-amino-2-methylpropanol, and 4,4-dimethyloxazoline group, obtained after cyclization of amides. In the steroid skeleton oxo groups were introduced in position 7 (2, 2a, 2b) and 7,12 (3, 3a, 3b). Ethylidene groups were introduced regio- and stereoselectively on C-7, and/or without stereoselectivity on C-3 by Wittig reaction. By combination of these modifications, a series of 19 bile acid derivatives were synthesized. Compounds containing both C-7 ethylidene and C-12 carbonyl groups (6, 6a, 6b) shown very good antitumor activity with IC 50 amide or oxazoline group has positive effect on cytotoxicity. Different molecular descriptors were determined in silico and after principal component analysis was found that molecular descriptor BLTF96 can be used for fast assessment of experimental cytotoxicity of bile acid derivatives. Copyright © 2017 Elsevier Inc. All rights reserved.

Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

Directory of Open Access Journals (Sweden)

Young-il Kim

Full Text Available Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA, which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA, which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.

Hybrid conducting polymer materials incorporating poly-oxo-metalates for extraction of actinides; Materiaux polymeres conducteurs hybrides incorporant des polyoxometallates pour l'extraction d'actinides

Energy Technology Data Exchange (ETDEWEB)

Racimor, D

2003-09-15

The preparation and characterization of hybrid conducting polymers incorporating poly-oxo-metalates for extracting actinides is discussed. A study of the coordination of various lanthanide cations (Ce(III), Ce(IV), Nd(III)) by the mono-vacant poly-oxo-metalate {alpha}{sub 2}-[P{sub 2}W{sub 17}O{sub 61}]{sup 10-} showed significant differences according to the cation.. Various {alpha}-A-[PW{sub 9}O{sub 34}(RPO){sub 2}]{sup 5-} hybrids were synthesized and their affinity for actinides or lanthanides was demonstrated through complexation. The first hybrid poly-oxo-metallic lanthanide complexes were then synthesized, as was the first hybrid functionalized with a pyrrole group. The electro-polymerization conditions of this pyrrole remain still to be optimized. Poly-pyrrole materials incorporating {alpha}{sub 2}-[P{sub 2}W{sub 17}O{sub 61}]{sup 10-} or its neodymium or cerium complexes as doping agents proved to be the first conducting polymer incorporating poly-oxo-metalates capable of extracting plutonium from nitric acid. (author)

Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

Science.gov (United States)

Hertz, Rachel; Kalderon, Bella; Byk, Tamara; Berman, Ina; Za'tara, Ghadeer; Mayer, Raphael; Bar-Tana, Jacob

2005-07-01

Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

Solution structures of lipoyl domains of the 2-oxo acid dehydrogenase complexes from Azotobacter vinelandii : implications for molecular recognition

NARCIS (Netherlands)

Berg, A.

1997-01-01

The 2-oxo acid dehydrogenase complexes are large multienzyme complexes that catalyse the irreversible oxidative decarboxylation of a specific 2-oxo acid to the corresponding acyl-CoA derivative. The pyruvate dehydrogenase complex (PDHC) converts the product of the glycolysis, pyruvate, to

[Perissodactyla: the primary structure of hemoglobins from the lowland tapir (Tapirus terrestris): glutamic acid in position 2 of the beta chains].

Science.gov (United States)

Mazur, G; Braunitzer, G

1984-09-01

The hemoglobins from a lowland tapir (Tapirus terrestris) were analysed and the complete primary structure is described. The globin chains were separated on CM cellulose column in 8M urea and the amino-acid sequences were determined in the liquid phase sequenator. The results show that globin consists of two alpha chains (alpha I and alpha II) and beta major and beta minor components. The alpha chains differ only at one position: alpha I contains aspartic acid and alpha II glycine. The beta chains are heterogeneous: aspartic and glutamic acid were found at position beta 21 and beta 73 of the beta major components and asparagine and serine at position beta 139. In the beta minor components four positions were found with more than one amino acid, namely beta 2, beta 4, beta 6 and beta 56. The sequences are compared with those of man, horse and rhinoceros. Four residues of horse methemoglobin, which are involved in the alpha 1 beta 1 contacts are substituted in tapir hemoglobins. In the alpha chains: alpha 107(G14)Ser----Val, alpha 111-(G18) Val----Leu, alpha 115(GH3) Asn----Asp or Gly; in the beta chains: beta 116(G18) Arg----Gln. The amino acid at beta 2 of the major components is glutamic acid while glutamine and histidine are found in the minor components. Although glutamic acid, a binding site for ATP, does not interact with 2,3-bisphosphoglycerate, glutamine and histidine in the minor components are responsible for the slight effect of 2,3-bisphosphoglycerate on tapir hemoglobin.

Positioning of the carboxamide side chain in 11-oxo-11H-indeno[1,2-b]quinolinecarboxamide anticancer agents: effects on cytotoxicity.

Science.gov (United States)

Deady, L W; Desneves, J; Kaye, A J; Finlay, G J; Baguley, B C; Denny, W A

2001-02-01

A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked cationic side chain at various positions on the chromophore was studied to determine structure-activity relationships between cytotoxicity and the position of the side chain. The compounds were prepared by Pfitzinger synthesis from an appropriate isatin and 1-indanone, followed by various oxidative steps, to generate the required carboxylic acids. The 4- and 6-carboxamides (with the side chain on a terminal ring, off the short axis of the chromophore) were effective cytotoxins. The dimeric 4- and 6-linked analogues were considerably more cytotoxic than the parent monomers, but had broadly similar activities. In contrast, analogues with side chains at the 8-position (on a terminal ring but off the long axis of the chromophore) or 10-position (off the short axis of the chromophore but in a central ring) were drastically less effective. The 4,10- and 6,10-biscarboxamides had activities between those of the corresponding parent monocarboxamides. The first of these showed good activity against advanced subcutaneous colon 38 tumours in mice.

Chain length dependence of the helix orientation in Langmuir-Blodgett monolayers of alpha-helical diblock copolypeptides

NARCIS (Netherlands)

Nguyen, Le-Thu T.; Ardana, Aditya; Vorenkamp, Eltjo J.; ten Brinke, Gerrit; Schouten, Arend J.

2010-01-01

The effect of chain length on the helix orientation of alpha-helical diblock copolypeptides in Langmuir and Langmuir-Blodgett monolayers is reported for the first time. Amphiphilic diblock copolypeptides (PLGA-b-PMLGSLGs) of poly(alpha-L-glutamic acid) (PLGA) and

Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma.

Science.gov (United States)

Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

2014-12-01

Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. © 2014 The British Pharmacological Society.

Determination of branched chain amino acids, methionine, phenylalanine, tyrosine and alpha-keto acids in plasma and dried blood samples using HPLC with fluorescence detection.

Science.gov (United States)

Kand'ár, Roman; Záková, Pavla; Jirosová, Jana; Sladká, Michaela

2009-01-01

The determination of branched chain amino acids [BCAA; valine (Val), leucine (Leu), isoleucine (Ile)], alpha-keto acids derived from BCAA [BCKA; alpha-ketoisovaleric acid (KIV), alpha-ketoisocaproic acid (KIC), alpha-ketomethylvaleric acid (KMV)], methionine (Met), phenylalanine (Phe) and tyrosine (Tyr) is currently the most reliable approach for the diagnosis of maple syrup urine disease (MSUD), hypermethioninemia, phenylketonuria (PKU) and tyrosinemia. The aim of this study was to develop rapid and simple HPLC methods for measurement of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples. Samples of peripheral venous blood with EDTA as anticoagulant were obtained from a group of healthy blood donors (n=70, 35 females, 27-41 years of age and 35 males, 28-43 years of age). Blood-spot samples from a group of newborns (n=80, 40 girls and 40 boys 3-5 days of age) were collected onto #903 Specimen Collection Paper and allowed to dry for at least 24 h before analysis. Prior to separation, the amino acids (AA) were derivatized with o-phthaldialdehyde (OPA) and BCKA with o-phenylenediamine (OPD). Reverse phase column chromatography (LiChroCart 125-4 Purospher RP-18e, 5 microm) was used for separation and fluorescence detection used to monitoring of effluent. For AA analysis, 25 mmol/L sodium hydrogenphosphate-methanol (90:10, v/v), pH 6.5+/-0.1 was used as mobile phase A and 100% methanol was used as mobile phase B. Measurement of BCKA used a mixture of methanol and deionized water (55:45, v/v) as mobile phase A and mobile phase B consisted of 100% methanol. Analytical performance of these methods was satisfactory for the determination of all AA and BCKA. The intra-assay and inter-assay coefficients of variation were below 10% and recovery ranged from 90%-110%. We have developed simple, rapid and selective HPLC methods with fluorescence detection for the determination of BCAA, Met, Phe, Tyr and BCKA in plasma and dried blood samples.

Nucleation-growth of salicylic acid-oxoTiO{sub 2} colloids synthesized by sol-gel processing

Energy Technology Data Exchange (ETDEWEB)

Tieng, S.; Jia, Z. [Laboratoire des Sciences des Procédés et des Matériaux, CNRS, Université Paris 13, Sorbonne Paris Cité, 99 avenue J.-B. Clément, 93430 Villetaneuse (France); Subra-Paternault, P. [Laboratoire de Chimie et Biologie des Membranes et Nanoobjets, CBMN – UMR 5248, Bâtiment, 14B, Allée Geoffroy Saint Hilaire, 33600 Pessac (France); Kanaev, A. [Laboratoire des Sciences des Procédés et des Matériaux, CNRS, Université Paris 13, Sorbonne Paris Cité, 99 avenue J.-B. Clément, 93430 Villetaneuse (France); Chhor, K., E-mail: khay.chhor@lspm.cnrs.fr [Laboratoire des Sciences des Procédés et des Matériaux, CNRS, Université Paris 13, Sorbonne Paris Cité, 99 avenue J.-B. Clément, 93430 Villetaneuse (France)

2014-12-15

In this work, the preparation of hybrid oxo-TiO{sub 2} nanoparticles modified by salicylic acid (SA) is reported. The size-selected TiO{sub 2} nanoparticles were synthesized in a sol-gel reactor with rapid micromixing of reagents and binding of SA molecules occurs at the nucleation stage. UV-visible absorption, Raman spectroscopy and Light scattering measurements evidence the formation of a SA–oxo-TiO{sub 2} charge-transfer complex. In particularly, the C=O vibration mode of SA shifts to lower frequencies upon complexation while the C-O vibration modes of both carboxylate and phenolic groups retain their position. The absence of C-O shift comes from two effects that cancel each other, i.e. the hardening of this mode related to the C=O mode changes and its softening due to the replacement of hydrogen in COH group by Ti atoms. Kinetic studies of the oxo-TiO{sub 2} nanoparticles nucleation and growth in presence of SA show that the acidic ligand at the nanoparticle surface acts as an attractor for another oxo-TiO{sub 2} nanoparticle leading to polycondensation. This mechanism is responsible for the acceleration of the nanoparticle aggregation kinetics and shortening of the induction time. The hybrid nanoparticles are stable at pH ≤ 7.7 and release SA molecules at pH ≥ 8.5. - Highlights: • Hybrid oxo-TiO{sub 2} nanoparticles modified by salicylic acid (SA) are prepared. • The synthesis is achieved during the nucleation stage of sol-gel process. • The formation of SA–oxo-TiO{sub 2} charge-transfer complex is evidenced. • Mechanism responsible for the acceleration of the nanoparticle aggregation kinetics is proposed. • SA-TiO{sub 2} nanoparticles are stable at pH ≤ 7.7 and release SA molecules at pH ≥ 8.5.

Retention data of bile acids and their oxo derivatives in characterization of pharmacokinetic properties and in silico ADME modeling.

Science.gov (United States)

Trifunović, Jovana; Borčić, Vladan; Vukmirović, Saša; Kon, Svetlana Goločorbin; Mikov, Momir

2016-09-20

Information on ADME properties of examined bile acids and their oxo derivatives are scarce, although the interest for bile acids and their use in nanochemistry and macromolecular chemistry is increasing. The purpose of this research was to evaluate the lipophilicity, a crucial physicochemical parameter for describing ADME properties of selected bile acids and their oxo derivatives, and to compare two approaches: experimentally determined hydrophobicity parameters and calculated logP values. Commercially available bile acids - deoxycholic, chenodeoxycholic, hyodeoxycholic and ursodeoxycholic acid were used to synthesize oxo derivatives. Lipophilicity was evaluated in two solvent systems: toluene/ethanol and toluene/butanol. Retention parameters were acquired by normal-phase TLC. The correlations between calculated logP values obtained using five different software and experimentally determined hydrophobicity parameters (RM(0)(tol/eth), RM(0)(tol/but), b(tol/eth) and b(tol/but)) were examined. Correlation analysis confirmed significant dependence between experimental RM(0) values and software calculated parameters. Results suggest satisfactory intestinal absorption after oral administration for all of the examined compounds as well as low volumes of distribution, and high affinity for binding with plasma proteins. Penetration through blood-brain barrier and skin is not satisfactory. All of the examined compounds show high affinity for binding with G-protein coupled receptors and consequently inhibition of ionic channels. Results also suggest possible binding with nuclear receptors. Established lipophilicity testing model of studied compounds showed excellent predictive ability and might represent significant tool in development of relations between chromatographic behavior and ADME properties. Compounds 3α-hydroxy-7,12-dioxo-5β-cholanoic and 12α-hydroxy-3,7-dioxo-5β-cholanoic acid might be the most suitable candidates for further development studies (satisfactory

Long-chain polyunsaturated fatty acids in maternal and infant nutrition

NARCIS (Netherlands)

Muskiet, Frits A. J.; van Goor, Saskia A.; Kuipers, Remko S.; Velzing-Aarts, Francien V.; Smit, Ella N.; Bouwstra, Hylco; Dijck-Brouwer, D. A. Janneke; Boersma, E. Rudy; Hadders-Algra, Mijna

Homo sapiens has evolved on a diet rich in alpha-linolenic acid and long chain polyunsaturated fatty acids (LCP). We have, however, gradually changed our diet from about 10,000 years ago and accelerated this change from about 100 to 200 years ago. The many dietary changes, including lower intake of

Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

Energy Technology Data Exchange (ETDEWEB)

May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

1987-06-01

Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

Identification of a novel bile acid in swans, tree ducks, and geese: 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.

Science.gov (United States)

Kakiyama, Genta; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio; Hagey, Lee R; Schteingart, Claudio D; Hofmann, Alan F

2006-07-01

By HPLC, a taurine-conjugated bile acid with a retention time different from that of taurocholate was found to be present in the bile of the black-necked swan, Cygnus melanocoryphus. The bile acid was isolated and its structure, established by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The compound was shown to have chromatographic and spectroscopic properties that were identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the subfamily Anserinae (swans and geese) but not in other subfamilies in the Anatidae family. It was also not present in species from the other two families of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic acid is a new primary bile acid that is present in the biliary bile acids of swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic acid.

Evolution of the biosynthesis of the branched-chain amino acids

Science.gov (United States)

Keefe, Anthony D.; Lazcano, Antonio; Miller, Stanley L.

1995-01-01

The origins of the biosynthetic pathways for the branched-chain amino acids cannot be understood in terms of the backwards development of the present acetolactate pathway because it contains unstable intermediates. We propose that the first biosynthesis of the branched-chain amino acids was by the reductive carboxylation of short branched chain fatty acids giving keto acids which were then transaminated. Similar reaction sequences mediated by nonspecific enzymes would produce serine and threomine from the abundant prebiotic compounds glycolic and lactic acids. The aromatic amino acids may also have first been synthesized in this way, e.g. tryptophan from indole acetic acid. The next step would have been the biosynthesis of leucine from alpha-ketoisovalerc acid. The acetolactate pathway developed subsequently. The first version of the Krebs cycle, which was used for amino acid biosynthesis, would have been assembled by making use fo the reductive carboxylation and leucine biosynthesis enzymes, and completed with the development of a single new enzyme, succinate dehydrogenase. This evolutionary scheme suggests that there may be limitations to inferring the origins of metabolism by a simple back extrapolation of current pathways.

Construction and characterization of the alpha form of a cardiac myosin heavy chain cDNA clone and its developmental expression in the Syrian hamster.

OpenAIRE

Liew, C C; Jandreski, M A

1986-01-01

A cDNA clone, pVHC1, was isolated from a Syrian hamster heart cDNA library and was compared to the rat alpha (pCMHC21) and beta (pCMHC5) ventricular myosin heavy chain cDNA clones. The DNA sequence and amino acid sequence deducted from the DNA show more homology with pCMHC21 than pCMHC5. This indicates that pVHC1 is an alpha ventricular myosin heavy chain cDNA clone. However, even though pVHC1 shows a high degree of nucleotide and amino acid conservation with the rat myosin heavy chain sequen...

Physiological covalent regulation of rat liver branched-chain alpha-ketoacid dehydrogenase

International Nuclear Information System (INIS)

Harris, R.A.; Powell, S.M.; Paxton, R.; Gillim, S.E.; Nagae, H.

1985-01-01

A radiochemical assay was developed for measuring branched-chain alpha-ketoacid dehydrogenase activity of Triton X-100 extracts of freeze-clamped rat liver. The proportion of active (dephosphorylated) enzyme was determined by measuring enzyme activities before and after activation of the complex with a broad-specificity phosphoprotein phosphatase. Hepatic branched-chain alpha-ketoacid dehydrogenase activity in normal male Wistar rats was 97% active but decreased to 33% active after 2 days on low-protein (8%) diet and to 13% active after 4 days on the same diet. Restricting protein intake of lean and obese female Zucker rats also caused inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex. Essentially all of the enzyme was in the active state in rats maintained for 14 days on either 30 or 50% protein diets. This was also the case for rats maintained on a commercial chow diet (minimum 23% protein). However, maintaining rats on 20, 8, and 0% protein diets decreased the percentage of the active form of the enzyme to 58, 10, and 7% of the total, respectively. Fasting of chow-fed rats for 48 h had no effect on the activity state of hepatic branched-chain alpha-ketoacid dehydrogenase, i.e., 93% of the enzyme remained in the active state compared to 97% for chow-fed rats. However, hepatic enzyme of rats maintained on 8% protein diet was 10% active before starvation and 83% active after 2 days of starvation. Thus, dietary protein deficiency results in inactivation of hepatic branched-chain alpha-ketoacid dehydrogenase complex, presumably as a consequence of low hepatic levels of branched-chain alpha-ketoacids

A concise synthesis of the potent inflammatory mediator 5-oxo-ETE

DEFF Research Database (Denmark)

Tyagi, Rahul; Shimpukade, Bharat; Blättermann, Stefanie

2012-01-01

A concise and practical method for synthesis of the potent inflammatory mediator 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE, 1) from arachidonic acid in four steps and 70% overall yield is reported. Stability studies indicate that 1 can be safely handled without rigorous precautions...

Overproduction of alpha chains provides a proton-insensitive component to the bluefish hemoglobin system.

Science.gov (United States)

Bonaventura, Celia; Godette, Gerald; Stevens, Robert; Brenowitz, Michael; Henkens, Robert

2005-12-09

Expression of alpha and beta chains and their post-translational assembly into alpha(2)beta(2) tetramers is fundamental to the formation and function of most vertebrate hemoglobins. There is a strong evolutionary bias that favors expression of equal amounts of the two types of chains, because cooperativity, pH sensitivity, and anionic control of function occurs only for the alpha(2)beta(2) tetramers. Remarkably, an over-production of alpha chains, as in the pathological condition known as beta thalassemia in humans, is adaptive rather than pathological in the bluefish hemoglobin system. The thalassemia of the bluefish is a novel means of providing for oxygen uptake and delivery when low pH conditions incapacitate the highly pH-sensitive Root effect hemoglobins of the fish. Although fish often have pH-insensitive along with highly pH-sensitive hemoglobins, having pH-insensitive alpha chain monomers in circulation is an unusual structural variation. The role of bluefish alpha chains in oxygen transport is enabled by their remarkably lower oxygen affinity relative to human alpha chains. This is the first reported case of a thalassemic condition that is maintained in a species as an adaptive advantage.

Epitope mapping of the alpha-chain of the insulin-like growth factor I receptor using antipeptide antibodies.

Science.gov (United States)

Delafontaine, P; Ku, L; Ververis, J J; Cohen, C; Runge, M S; Alexander, R W

1994-12-01

Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells (VSMC). The IGF I receptor (IGF IR) is a heterotetramer composed of two cross-linked extracellular alpha-chains and two membrane-spanning beta-chains that contain a tyrosine-kinase domain. It has a high degree of sequence similarity to the insulin receptor (IR), and the putative ligand-specific binding site has been localized to a cysteine-rich region (CRR) of the alpha-chain. To obtain insights into antigenic determinants of the IGF IR, we raised a panel of site-specific polyclonal antibodies against short peptide sequences N-terminal to and within the CRR. Several antibodies raised against linear epitopes within the CRR bound to solubilized and native rat and human IGF IR by ELISA, did not cross-react with IR, but unexpectedly failed to inhibit 125I-IGF I binding. A polyclonal antibody directed against a 48-amino acid synthetic peptide, corresponding to a region of the CRR postulated to be essential for ligand binding, failed to react with either solubilized, reduced or intact IGF IR. Three antibodies specific for the N-terminus of the alpha-chain reacted with solubilized and native IGF IR. One of these, RAB 6, directed against amino acids 38-44 of the IGF IR, inhibited 125I-IGF I binding to rat aortic smooth muscle cells (RASM) and to IGF IR/3T3 cells (overexpressing human IGF IR) by up to 45%. Immunohistochemical analysis revealed strong IGF IR staining in the medial smooth muscle cell layer of rat aorta. These findings are consistent with a model wherein conformational epitopes within the CRR and linear epitopes within the N-terminus of the alpha-chain contribute to the IGF I binding pocket. These antibodies should provide a valuable tool to study structure-function relationships and in vivo regulation of the IGF IR.

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Furumoto, Hidehiro; Nanthirudjanar, Tharnath [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kume, Toshiaki; Izumi, Yasuhiko [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Simoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Park, Si-Bum [Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Hirata, Takashi [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Faculty of Rehabilitation, Shijonawategakuen University, 5-11-10, Hojo, Daitou-shi, Osaka 574-0011 (Japan); Sugawara, Tatsuya, E-mail: sugawara@kais.kyoto-u.ac.jp [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan)

2016-04-01

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

International Nuclear Information System (INIS)

Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

2016-01-01

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

Influence of dietary long-chain n-3 fatty acids from menhaden fish oil on plasma concentrations of alpha-tocopherol in geriatric beagles.

Science.gov (United States)

Hall, Jean A; Tooley, Katie A; Gradin, Joseph L; Jewell, Dennis E; Wander, Rosemary C

2002-01-01

To determine effects of dietary n-3 fatty acids from Menhaden fish oil on plasma alpha-tocopherol concentrations in Beagles. 32 female Beagles. For 82 days, dogs were fed diets that contained 1 of 2 ratios of n-6:n-3 fatty acids (40:1 [low n-3] and 1.4:1 [high n-3]) and 1 of 3 concentrations of all-rac-alpha-tocopheryl acetate (low, 17 mg/kg of diet; medium, 101 mg/kg; and high, 447 mg/kg) in a 2 X 3 factorial study. Diets high in n-3 fatty acids significantly increased total content of n-3 fatty acids in plasma (17.0 g/100 g of fatty acids), compared with low n-3 diets (2.02 g/100 g of fatty acids). Mean +/- SEM plasma concentration of cholesterol was significantly lower in dogs consuming high n-3 diets (4.59 +/- 0.48 mmol/L), compared with dogs consuming low n-3 diets (5.71 +/- 0.48 mmol/L). A significant interaction existed between the ratio for n-6 and n-3 fatty acids and amount of alpha-tocopheryl acetate in the diet (plasma alpha-tocopherol concentration expressed on a molar basis), because the plasma concentration of alpha-toco-pherol was higher in dogs consuming low n-3 diets, compared with those consuming high n-3 diets, at the 2 higher amounts of dietary alpha-tocopheryl acetate. Plasma alpha-tocopherol concentration expressed relative to total lipid content did not reveal effects of dietary n-3 fatty acids on concentration of alpha-tocopherol. Plasma alpha-tocopherol concentration is not dependent on dietary ratio of n-6 and n-3 fatty acids when alpha-tocopherol concentration is expressed relative to the total lipid content of plasma.

Does alpha 1-acid glycoprotein act as a non-functional receptor for alpha 1-adrenergic antagonists?

Science.gov (United States)

Qin, M; Oie, S

1994-11-01

The ability of a variety of alpha 1-acid glycoproteins (AAG) to affect the intrinsic activity of the alpha 1-adrenergic antagonist prazosin was studied in rabbit aortic strip preparations. From these studies, the activity of AAG appears to be linked to their ability to bind the antagonist. However, a capability to bind prazosin was not the only requirement for this effect. The removal of sialic acid and partial removal of the galactose and mannose residues by periodate oxidation of human AAG all but eliminated the ability of AAG to affect the intrinsic pharmacologic activity of prazosin, although the binding of prazosin was not significantly affected. The presence of bovine AAG, a protein that has a low ability to bind prazosin, reduced the effect of human AAG on prazosin activity. Based upon these results, we propose that AAG is able to bind in the vicinity of the alpha 1-adrenoceptors, therefore extending the binding region for antagonists in such a way as to decrease the ability of the antagonist to interact with the receptor. The carbohydrate side-chains are important for the binding of AAG in the region of the adrenoceptor.

Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry

International Nuclear Information System (INIS)

Hofmann, U.; Seefried, S.; Meese, C.O.; Mettang, T.; Huebel, E.K.; Kuhlmann, U.

1990-01-01

Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man

10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis.

Science.gov (United States)

Goto, Tsuyoshi; Kim, Young-Il; Furuzono, Tomoya; Takahashi, Nobuyuki; Yamakuni, Kanae; Yang, Ha-Eun; Li, Yongjia; Ohue, Ryuji; Nomura, Wataru; Sugawara, Tatsuya; Yu, Rina; Kitamura, Nahoko; Park, Si-Bum; Kishino, Shigenobu; Ogawa, Jun; Kawada, Teruo

2015-04-17

Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increased adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Chain-modified radioiodinated fatty acids

International Nuclear Information System (INIS)

Otto, C.A.

1987-01-01

Several carbon chain manipulations have been studied in terms of their effects on myocardial activity levels and residence time. The manipulations examined included: chain length, chain branching, chain unsaturation, and carbon-iodine bond stabilization. It was found that chain length affects myocardial activity levels for both straight-chain alkyl acids and branched chain alkyl and aryl acids. Similar results have been reported for the straight-chain aryl acids. Generally, the longer chain lengths correlated with higher myocardial activity levels and longer residence times. This behavior is attributed to storage as triglycerides. Branched chain acids are designed to be anti-metabolites but only the aryl β-methyl acids possessed the expected time course of constant or very slowly decreasing activity levels. The alkyl β-methyl acids underwent rapid deiodination - a process apparently independent of β-oxidation. Inhibition of β-oxidation by incorporation of carbon-carbon double and triple bonds was studied. Deiodination of ω-iodo alkyl fatty acids prevented an assessment of suicide inhibition using an unsaturated alkynoic acid. Stabilization of the carbon-iodine bond by attachment of iodine to a vinylic or aryl carbon was studied. The low myocardial values and high blood values observed for an eleven carbon ω-iodo vinylic fatty acid were not encouraging but ω-iodo aryl fatty acids appear to avoid the problems of rapid deiodination. (Auth.)

Clofibric acid stimulates branched-chain amino acid catabolism by three mechanisms.

Science.gov (United States)

Kobayashi, Rumi; Murakami, Taro; Obayashi, Mariko; Nakai, Naoya; Jaskiewicz, Jerzy; Fujiwara, Yoko; Shimomura, Yoshiharu; Harris, Robert A

2002-11-15

Clofibrate promotes catabolism of branched-chain amino acids by increasing the activity of the branched-chain alpha-keto acid dehydrogenase [BCKDH] complex. Depending upon the sex of the rats, nutritional state, and tissue being studied, clofibrate can affect BCKDH complex activity by three different mechanisms. First, by directly inhibiting BCKDH kinase activity, clofibrate can increase the proportion of the BCKDH complex in the active, dephosphorylated state. This occurs in situations in which the BCKDH complex is largely inactive due to phosphorylation, e.g., in the skeletal muscle of chow-fed rats or in the liver of female rats late in the light cycle. Second, by increasing the levels at which the enzyme components of the BCKDH complex are expressed, clofibrate can increase the total enzymatic activity of the BCKDH complex. This is readily demonstrated in livers of rats fed a low-protein diet, a nutritional condition that induces a decrease in the level of expression of the BCKDH complex. Third, by decreasing the amount of BCKDH kinase expressed and therefore its activity, clofibrate induces an increase in the percentage of the BCKDH complex in the active, dephosphorylated state. This occurs in the livers of rats fed a low-protein diet, a nutritional condition that causes inactivation of the BCKDH complex due to upregulation of the amount of BCKDH kinase. WY-14,643, which, like clofibric acid, is a ligand for the peroxisome-proliferator-activated receptor alpha [PPARalpha], does not directly inhibit BCKDH kinase but produces the same long-term effects as clofibrate on expression of the BCKDH complex and its kinase. Thus, clofibrate is unique in its capacity to stimulate BCAA oxidation through inhibition of BCKDH kinase activity, whereas PPARalpha activators in general promote BCAA oxidation by increasing expression of components of the BCKDH complex and decreasing expression of the BCKDH kinase.

Single-Step Access to Long-Chain α,ω-Dicarboxylic Acids by Isomerizing Hydroxycarbonylation of Unsaturated Fatty Acids

KAUST Repository

Goldbach, Verena

2016-11-09

Dicarboxylic acids are compounds of high value, but to date long-chain alpha,omega-dicarboxylic acids have been difficult to access in a direct way. Unsaturated fatty acids are ideal starting materials with their molecular structure of long methylene sequences and a carboxylate functionality, in addition to a double bond that offers itself for functionalization. Within this paper, we established a direct access to alpha,omega-dicarboxylic acids by combining isomerization and selective terminal carbonylation of the internal double bond with water as a nucleophile on unsaturated fatty acids. We identified the key elements of this reaction: a homogeneous reaction mixture ensuring sufficient contact between all reactants and a catalyst system allowing for activation of the Pd precursor under aqueous conditions. Experiments under pressure reactor conditions with [(dtbpx)Pd(OTf)(2)] as catalyst precursor revealed the importance of nucleophile and reactant concentrations and the addition of the diprotonated diphosphine ligand (dtbpxH(2))(OTf)(2) to achieve turnover numbers >120. A variety of unsaturated fatty acids, including a triglyceride, were converted to valuable long-chain dicarboxylic acids with high turnover numbers and selectivities for the linear product of >90%. We unraveled the activation pathway of the Pd-II precursor, which proceeds via a reductive elimination step forming a Pd species and oxidative addition of the diprotonated diphosphine ligand, resulting in the formation of the catalytically active Pd hydride species. Theoretical calculations identified the hydrolysis as the rate-determining step. A low nucleophile concentration in the reaction mixture in combination with this high energetic barrier limits the potential of this reaction. In conclusion, water can be utilized as a nucleophile in isomerizing functionalization reactions and gives access to long-chain dicarboxylic acids from a variety of unsaturated substrates. The activity of the catalytic

Degradation of oxo-biodegradable plastic by Pleurotus ostreatus.

Science.gov (United States)

da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Nunes, Mateus Dias; da Silva, Marliane de Cássia Soares; Kasuya, Maria Catarina Megumi

2013-01-01

Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ultraviolet light (UV) or heat can lead to breakage of the polymer chains in the plastic, and the resulting compounds are easily degraded by microorganisms. However, few studies have characterized the microbial degradation of oxo-biodegradable plastics. In this study, we tested the capability of Pleurotus ostreatus to degrade oxo-biodegradable (D2W) plastic without prior physical treatment, such as exposure to UV or thermal heating. After 45 d of incubation in substrate-containing plastic bags, the oxo-biodegradable plastic, which is commonly used in supermarkets, developed cracks and small holes in the plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen bonds. These alterations may be due to laccase activity. Furthermore, we observed the degradation of the dye found in these bags as well as mushroom formation. Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms using this plastic as substrate.

Degradation of oxo-biodegradable plastic by Pleurotus ostreatus.

Directory of Open Access Journals (Sweden)

José Maria Rodrigues da Luz

Full Text Available Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ultraviolet light (UV or heat can lead to breakage of the polymer chains in the plastic, and the resulting compounds are easily degraded by microorganisms. However, few studies have characterized the microbial degradation of oxo-biodegradable plastics. In this study, we tested the capability of Pleurotus ostreatus to degrade oxo-biodegradable (D2W plastic without prior physical treatment, such as exposure to UV or thermal heating. After 45 d of incubation in substrate-containing plastic bags, the oxo-biodegradable plastic, which is commonly used in supermarkets, developed cracks and small holes in the plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen bonds. These alterations may be due to laccase activity. Furthermore, we observed the degradation of the dye found in these bags as well as mushroom formation. Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms using this plastic as substrate.

Degradation of Oxo-Biodegradable Plastic by Pleurotus ostreatus

Science.gov (United States)

da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Nunes, Mateus Dias; da Silva, Marliane de Cássia Soares; Kasuya, Maria Catarina Megumi

2013-01-01

Growing concerns regarding the impact of the accumulation of plastic waste over several decades on the environmental have led to the development of biodegradable plastic. These plastics can be degraded by microorganisms and absorbed by the environment and are therefore gaining public support as a possible alternative to petroleum-derived plastics. Among the developed biodegradable plastics, oxo-biodegradable polymers have been used to produce plastic bags. Exposure of this waste plastic to ultraviolet light (UV) or heat can lead to breakage of the polymer chains in the plastic, and the resulting compounds are easily degraded by microorganisms. However, few studies have characterized the microbial degradation of oxo-biodegradable plastics. In this study, we tested the capability of Pleurotus ostreatus to degrade oxo-biodegradable (D2W) plastic without prior physical treatment, such as exposure to UV or thermal heating. After 45 d of incubation in substrate-containing plastic bags, the oxo-biodegradable plastic, which is commonly used in supermarkets, developed cracks and small holes in the plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen bonds. These alterations may be due to laccase activity. Furthermore, we observed the degradation of the dye found in these bags as well as mushroom formation. Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms using this plastic as substrate. PMID:23967057

Alpha Hydroxy Acids

Science.gov (United States)

... or tenderness (8), chemical burns (6), and increased sunburn (3). The frequency of such reports for skin ... bear a statement that conveys the following information: Sunburn Alert: This product contains an alpha hydroxy acid ( ...

10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

Energy Technology Data Exchange (ETDEWEB)

Goto, Tsuyoshi, E-mail: tgoto@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University (Japan); Kim, Young-Il; Furuzono, Tomoya [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University (Japan); Yamakuni, Kanae; Yang, Ha-Eun; Li, Yongjia [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Ohue, Ryuji [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University (Japan); Nomura, Wataru [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Sugawara, Tatsuya [Laboratory of Marine Bioproducts Technology, Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502 (Japan); Yu, Rina [Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749 (Korea, Republic of); Kitamura, Nahoko [Laboratory of Fermentation Physiology and Applied Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502 (Japan); and others

2015-04-17

Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increased adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. - Highlights: • Most LA-derived fatty acids from gut lactic acid bacteria potently activated PPARα. • Among tested fatty acids, KetoA and KetoC significantly activated PPARγ. • KetoA induced adipocyte differentiation via the activation of PPARγ. • KetoA enhanced adiponectin production and glucose uptake during adipogenesis.

10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

International Nuclear Information System (INIS)

Goto, Tsuyoshi; Kim, Young-Il; Furuzono, Tomoya; Takahashi, Nobuyuki; Yamakuni, Kanae; Yang, Ha-Eun; Li, Yongjia; Ohue, Ryuji; Nomura, Wataru; Sugawara, Tatsuya; Yu, Rina; Kitamura, Nahoko

2015-01-01

Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increased adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. - Highlights: • Most LA-derived fatty acids from gut lactic acid bacteria potently activated PPARα. • Among tested fatty acids, KetoA and KetoC significantly activated PPARγ. • KetoA induced adipocyte differentiation via the activation of PPARγ. • KetoA enhanced adiponectin production and glucose uptake during adipogenesis

The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4{alpha}

Energy Technology Data Exchange (ETDEWEB)

Klapper, Maja [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Boehme, Mike [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Nitz, Inke [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Doering, Frank [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany)

2007-04-27

The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4{alpha} (HNF-4{alpha}), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4{alpha} binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4{alpha} by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4{alpha}, that are both candidate genes for diabetes type 2, may be a powerful approach.

Terminal Gold-Oxo Complexes

Energy Technology Data Exchange (ETDEWEB)

Cao, R.; Anderson, T.M.; Piccoli, P.M.B.; Schultz, A.J.; Koetzle, T.F.; Geletii, Y.V.; Slonkina, E.; Hedman, B.; Hodgson, K.O.; Hardcastle, K.I.; Fang, X.; Kirk, M.L.; Knottenbelt, S.; Kogerler, P.; Musaev, D.G.; Morokuma, K.; Takahashi, M.; Hill, C.L.; /Emory U. /Argonne /SLAC, SSRL /New Mexico U. /Iowa State U. /Toho U.

2007-10-19

In contradiction to current bonding paradigms, two terminal Au-oxo molecular complexes have been synthesized by reaction of AuCl{sub 3} with metal oxide-cluster ligands that model redox-active metal oxide surfaces. Use of K{sub 10}[{alpha}{sub 2}-P{sub 2}W{sub 17}O{sub 61}] x 20H{sub 2}O and K{sub 2}WO{sub 4} (forming the [A-PW{sub 9}O{sub 34}]{sup 9-} ligand in situ) produces K{sub 15}H{sub 2}[Au(O)(OH{sub 2})P{sub 2}W{sub 18}O{sub 68}] x 25H{sub 2}O (1); use of K{sub 10}[P{sub 2}W{sub 20}O{sub 70}(OH{sub 2}){sub 2}] x 22H{sub 2}O (3) produces K{sub 7}H{sub 2}[Au(O)(OH{sub 2})P{sub 2}W{sub 20}O{sub 70}(OH{sub 2}){sub 2}] x 27H{sub 2}O (2). Complex 1 crystallizes in orthorhombic Fddd, with a = 28.594(4) Angstroms, b = 31.866(4) Angstroms, c = 38.241(5) Angstroms, V = 34844(7) Angstroms{sup 3}, Z = 16 (final R = 0.0540), and complex 2 crystallizes in hexagonal P6(3)/mmc, with a = 16.1730(9) Angstroms, b = 16.1730(9) Angstroms, c = 19.7659(15) Angstroms, V = 4477.4(5) Angstroms{sup 3}, Z = 2 (final R = 0.0634). The polyanion unit in 1 is disorder-free. Very short ({approx}1.76 Angstroms) Au-oxo distances are established by both X-ray and 30 K neutron diffraction studies, and the latter confirms oxo and trans aqua (H2O) ligands on Au. Seven findings clarify that Au and not W is present in the Au-oxo position in 1 and 2. Five lines of evidence are consistent with the presence of d8 Au(III) centers that are stabilized by the flanking polytungstate ligands in both 1 and 2: redox titrations, electrochemical measurements, 17 K optical spectra, Au L2 edge X-ray absorption spectroscopy, and Au-oxo bond distances. Variable-temperature magnetic susceptibility data for crystalline 1 and 2 establish that both solids are diamagnetic, and {sup 31}P and {sup 17}O NMR spectroscopy confirm that both remain diamagnetic in solution. Both complexes have been further characterized by FT-IR, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and other techniques.

α-Oxo-Ketenimines from Isocyanides and α-Haloketones: Synthesis and Divergent Reactivity.

Science.gov (United States)

Mamboury, Mathias; Wang, Qian; Zhu, Jieping

2017-09-18

The palladium-catalyzed reaction of α-haloketones with isocyanides afforded α-oxo-ketenimines through β-hydride elimination of the β-oxo-imidoyl palladium intermediates. Reaction of these relatively stable α-oxo-ketenimines with nucleophiles such as hydrazines, hydrazoic acid, amines, and Grignard reagent afforded pyrazoles, tetrazole, β-keto amidines, and enaminone, respectively, with high chemoselectivity. Whereas amines attack exclusively on the ketenimine functions, the formal [3+2] cycloaddition between N-monosubstituted hydrazines and α-oxo-ketenimines was initiated by nucleophilic addition to the carbonyl group. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery of an imidazopyridine-containing 1,4-benzodiazepine nonpeptide vitronectin receptor (alpha v beta 3) antagonist with efficacy in a restenosis model.

Science.gov (United States)

Keenan, R M; Lago, M A; Miller, W H; Ali, F E; Cousins, R D; Hall, L B; Hwang, S M; Jakas, D R; Kwon, C; Louden, C; Nguyen, T T; Ohlstein, E H; Rieman, D J; Ross, S T; Samanen, J M; Smith, B R; Stadel, J; Takata, D T; Vickery, L; Yuan, C C; Yue, T L

1998-11-17

In the 3-oxo-1,4-benzodiazepine-2-acetic acid series of vitronectin receptor (alpha v beta 3) antagonists, a compound containing an imidazopyridine arginine mimetic was discovered which had sufficient potency and i.v. pharmacokinetics for demonstration of efficacy in a rat restenosis model.

Conformationally constrained dipeptide surrogates with aromatic side-chains: synthesis of 4-aryl indolizidin-9-one amino acids by conjugate addition to a common alpha,omega-diaminoazelate enone intermediate.

Science.gov (United States)

Cluzeau, Jérôme; Lubell, William D

2004-03-05

Four methyl 9-oxo-8-(N-(Boc)-amino)-4-phenyl-1-azabicyclo[4.3.0]nonane carboxylates (11, 4-Ph-I(9)aa-OMe) were synthesized from (2S,8S,5E)-di-tert-butyl-4-oxo-5-ene-2,8-bis[N-(PhF)amino]azelate [(5E)-7, PhF = 9-(9-phenylfluorenyl)] via a seven-step process featuring a conjugate addition/reductive amination/lactam cyclization sequence. Various nucleophiles were used in the conjugate addition reactions on enone (5E)-7 as a general route for making alpha,omega-diaminoazelates possessing different substituents in good yield albeit low diastereoselectivity except in the case of aryl Grignard reagents (9/1 to 15/1 drs). 6-Phenylazelates (6S)-8d and (6R)-8d were separated by chromatography and diastereoselective precipitation and independently transformed into 4-Ph-I(9)aa-OMe. From (6S)-8d, (2S,4R,6R,8S)-4-Ph-I(9)aa-OMe 11 was prepared selectively in 51% yield. Reductive amination of (6R)-8d provided the desired pipecolates 9 along with desamino compound 10, which was minimized by performing the hydrogenation in the presence of ammonium acetate. Subsequent ester exchange, lactam cyclization, and amine protection provided three products (2R,4S,6S,8R)-, (2R,4S,6S,8S)-, and (2S,4S,6R,8S)-4-Ph-I(9)aa-OMe 11 in 10, 6, and 6% yields, respectively, from (6R)-8d. Ester hydrolysis of (2S,4R,6R,8S)-11 furnished 4-phenyl indolizidin-9-one N-(Boc)amino acid 3 as a novel constrained Ala-Phe dipeptide surrogate for studying conformation-activity relationships of biologically active peptides.

Resting state electroencephalographic correlates with red cell long-chain fatty acids, memory performance and age in adolescent boys with attention deficit hyperactivity disorder.

Science.gov (United States)

Sumich, Alexander; Matsudaira, Toshiko; Gow, Rachel V; Ibrahimovic, Almira; Ghebremeskel, Kebreab; Crawford, Michael; Taylor, Eric

2009-12-01

Abnormal fatty acid status has been implicated in the aetiology of attention deficit hyperactivity disorder (ADHD). Delayed maturation in ADHD may result in raised frontal low frequency (theta) electroencephalographic activity (EEG) and a reduction in posterior high frequency (beta, alpha) activity. The current study used sequential linear regression to investigate the association between age, resting-state EEG and levels of long-chain polyunsaturated omega-3 and omega-6 fatty acids in red blood cells in 46 adolescent boys with ADHD symptoms. Docosahexaenoic acid (DHA) levels were positively associated with fast frequency activity: alpha during eyes-open and beta during eyes-closed conditions. Frontal theta activity during both eyes-open and eyes-closed conditions was inversely associated with age and positively associated with eicosapentaenoic acid (EPA) levels. Alpha activity correlated positively with performance on fluency for categories (semantic memory). Theta activity correlated inversely with performance on delayed (25 min) verbal memory (recall + recognition/2). No associations were observed between long-chain omega-6 and EEG measures. Results support differential associations for DHA and EPA with fast and slow EEG activity respectively. Results support EEG activity as an objective biomarker of neural function associated with long-chain omega-3 fatty acids in ADHD.

Purification of 2-oxo acid dehydrogenase multienzyme complexes from ox heart by a new method.

OpenAIRE

Stanley, C J; Perham, R N

1980-01-01

A new method is described that allows the parallel purification of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multienzyme complexes from ox heart without the need for prior isolation of mitochondria. All the assayable activity of the 2-oxo acid dehydrogenase complexes in the disrupted tissue is made soluble by the inclusion of non-ionic detergents such as Triton X-100 or Tween-80 in the buffer used for the initial extraction of the enzyme complexes. The yields of the pyruvate...

Primary structure of the hemoglobin alpha-chain of rose-ringed parakeet (Psittacula krameri).

Science.gov (United States)

Islam, A; Beg, O U; Persson, B; Zaidi, Z H; Jörnvall, H

1988-10-01

The structure of the hemoglobin alpha-chain of Rose-ringed Parakeet was determined by sequence degradations of the intact subunit, the CNBr fragments, and peptides obtained by digestion with staphylococcal Glu-specific protease and trypsin. Using this analysis, the complete alpha-chain structure of 21 avian species is known, permitting comparisons of the protein structure and of avian relationships. The structure exhibits differences from previously established avian alpha-chains at a total of 61 positions, five of which have residues unique to those of the parakeet (Ser-12, Gly-65, Ser-67, Ala-121, and Leu-134). The analysis defines hemoglobin variation within an additional avian order (Psittaciformes), demonstrates distant patterns for evaluation of relationships within other avian orders, and lends support to taxonomic conclusions from molecular data.

Effect of preterm formula with and without long-chain polyunsaturated fatty acids on the urinary excretion of F2-isoprostanes and 8-epi-prostaglandin F2alpha.

Science.gov (United States)

Stier, C; Schweer, H; Jelinek, J; Watzer, B; Seyberth, H W; Leonhardt, A

2001-02-01

The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on the endogenous formation of F2-isoprostanes and 8-epi-prostaglandin (PG) F2alpha as possible markers of lipid peroxidation in preterm infants during their first weeks of life. In a prospective, randomized, double-blind study, infants received either formula enriched with LCP (n = 8), standard preterm formula (n = 7), or (expressed) breast milk (n = 8). Urine was sampled at study entry and after the study period of 3 weeks. The formation of F2-isoprostanes and 8-epi-PGF2alpha was evaluated by measuring the urinary excretion by gas chromatography-mass spectrometry. No differences in the urinary excretion of F2-isoprostanes and 8-epi-PGF2alpha were observed at the end of the study period. This result suggests that supplementation of a preterm formula with LCP for a period of 3 weeks does not stimulate lipid peroxidation in preterm infants.

Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

Directory of Open Access Journals (Sweden)

Somoza Veronika

2009-02-01

Full Text Available Abstract Background Conversion of linoleic acid (LA and alpha-linolenic acid (ALA to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA- and alpha-linolenic acid ([13C]ALA-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D and delta-6 desaturase (D6D, peroxisome proliferator-activated receptor alpha (PPARα and sterol regulatory element binding protein 1c (SREBP-1c. Mitogen-activated protein kinase kinase 1 (MEK1 and mitogen-activated protein kinase kinase kinase 1 (MEKK1 were also examined. Results Maximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

Metabolism of methylphenidate in dog and rat

International Nuclear Information System (INIS)

Egger, H.; Bartlett, F.; Dreyfuss, R.; Karliner, J.

1981-01-01

The urinary metabolites of methylphenidate in the dog and rat were investigated. After oral administration of 14C-labeled methylphenidate, approximately 86% and 63% of the dose was recovered in the urine of the dog and rat, respectively. Less than 1% of the dose was excreted as unchanged drug. Metabolism involved oxidation, hydrolysis, and conjugation processes. The primary hydrolytic product was alpha-phenyl-2-piperidineacetic acid (24%, dog; 35-40%, rat). The primary metabolites of oxidation were methyl 6-oxo-alpha-phenyl-2-piperidineacetate (3%, dog; 1.5%, rat) and the glucuronide of alpha-(p-hydroxyphenyl)-2-piperidineacetic acid (10%, rat). The former also underwent extensive biotransformation, including: 1) hydrolysis to the lactam acid (27%, dog; 7-10%, rat) and subsequent carboxylic acid O-glucuronidation (15%, dog); or 2) hydroxylation at the 5-position (1%, dog; 2%, rat) and subsequent hydrolysis (4%, dog; 15-17%, rat); or 3) 5-O-glucuronidation (12%, dog). Additional minor metabolites from methyl-6-oxo-alpha-phenyl-2-piperidineacetate were the phenolic O-glucuronide of methyl alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetate (1%, dog), and the 4-O-glucuronide of methyl 4-hydroxy-6-oxo-alpha-phenyl-2-piperidineacetate (1%, dog), and the taurine amide conjugate of alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetic acid (1%, dog). Additional products from methylphenidate conjugation included methyl 1-carbamoyl-alpha-phenyl-2-piperidineacetate (1%, dog or rat) and its carboxylic acid hydrolysis product (1%, rat). The chirality of the major metabolites isolated from dog urine showed that metabolism was partially stereoselective in all investigated cases, except in the formation of alpha-phenyl-2-piperidineacetic acid

Alpha-decay chains of superheavy nuclei 292-296118

Science.gov (United States)

Singh, U. K.; Kumawat, M.; Saxena, G.; Kaushik, M.; Jain, S. K.

2018-05-01

We have employed relativistic mean-field plus BCS (RMF+BCS) approach for the study of even-even superheavy nuclei with Z = 118 which is the last and recent observed element in the periodic chart so far. Our study includes binding energies, Qα values, alpha-decay half-lives and spontaneous decay half-lives along with comparison of available experimental data and the results of FRDM calculations. We find an excellent match with the only known decay chain of 294118 for Z = 118 so far and predict decay chain of 292118 and 296118 in consistency with known experimental decay chains and FRDM results. These results may provide a very helpful insight to conduct experiments for realizing the presence of nuclei with Z = 118.

Stability study on an anti-cancer drug 4-(3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl-4-oxo-2-butenoic acid (CLEFMA using a stability-indicating HPLC method

Directory of Open Access Journals (Sweden)

Dhawal Raghuvanshi

2017-02-01

Full Text Available CLEFMA, 4-(3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl-4-oxo-2-butenoic acid, is a new chemical entity with anti-cancer and anti-inflammatory activities. Here, we report its stability in solution against stress conditions of exposure to acid/base, light, oxidant, high temperature, and plasma. The identity of the degradation products was ascertained by mass and proton nuclear magnetic resonance spectroscopy. To facilitate this study, we developed and validated a reverse phase high performance liquid chromatography method for detection of CLEFMA and its degradation. The method was linear over a range of 1–100 µg/mL; the accuracy and precision were within acceptable limits; it was stability-indicating as it successfully separated cis-/trans-isomers of CLEFMA as well as its degradation product. The major degradation product was produced from amide hydrolysis at maleic acid functionality caused by an acidic buffer, oxidant (3% hydrogen peroxide, or temperature stress (40–60 °C. The log k-pH profile showed that CLEFMA was most stable at neutral pH. In accelerated stability study we found that the shelf-life (T90% of CLEFMA at 25 °C and 4 °C was 45 days and 220 days, respectively. Upon exposure to UV-light (365 nm, the normally prevalent trans-CLEFMA attained cis-configuration. This isomerization also involved the maleic acid moiety. CLEFMA was stable in plasma from which it could be efficiently extracted by an acetonitrile precipitation method. These results indicate that CLEFMA is sensitive to hydrolytic cleavage at its maleic acid moiety, and it is recommended that its samples should be stored under refrigerated and light-free conditions, and under inert environment.

OxymaPure/DIC: An Efficient Reagent for the Synthesis of a Novel Series of 4-[2-(2-Acetylaminophenyl-2-oxo-acetylamino] Benzoyl Amino Acid Ester Derivatives

Directory of Open Access Journals (Sweden)

Ayman El-Faham

2013-11-01

Full Text Available OxymaPure (ethyl 2-cyano-2-(hydroxyiminoacetate was tested as an additive for use in the carbodiimide (DIC approach for the synthesis of a novel series of α-ketoamide derivatives (4-[2-(2-acetylaminophenyl-2-oxo-acetylamino]benzoyl amino acid ester derivatives. OxymaPure showed clear superiority to HOBt/DIC or carbodiimide alone in terms of purity and yield. The title compounds were synthesized via the ring opening of N-acylisatin. First, N-acetylisatin was reacted with 4-aminobenzoic acid under conventional heating as well as microwave irradiation to afford 4-(2-(2-acetamidophenyl-2-oxoacetamidobenzoic acid. This α-ketoamide was coupled to different amino acid esters using OxymaPure/DIC as a coupling reagent to afford 4-[2-(2-acetylaminophenyl-2-oxo-acetylamino]benzoyl amino acid ester derivatives in excellent yield and purity. The synthesized compounds were characterized using FT-IR, NMR, and elemental analysis.

Production of 3-Oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic Acid in the Fungus Aspergillus oryzae: A Step Towards Heterologous Production of Pyrethrins in Fungi.

Science.gov (United States)

Mohamed, Maged E; Pahirulzaman, Khomaizon A K; Lazarus, Colin M

2016-03-01

Pyrethrins are natural insecticides, which accumulate to high concentrations in pyrethrum (Chrysanthemum cinerariaefolium) flowers. Synthetic pyrethroids are more stable, more efficacious and cheaper, but contemporary requirements for safe and environmentally friendly pesticides encourage a return to the use of natural pyrethrins, and this would be favoured by development of an efficient route to their production by microbial fermentation. The biosynthesis of pyrethrins involves ester linkage between an acid moiety (chrysanthemoyl or pyrethroyl, synthesised via the mevalonic acid pathway from glucose), and an alcohol (pyrethrolone). Pyrethrolone is generated from 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid, which originates from α-linolenic acid via the jasmonic acid biosynthetic cascade. The first four genes in this cascade, encoding lipoxygenase 2, allene-oxide synthase, allene-oxide cyclase 2 and 12-oxophytodienoic acid reductase 3, were amplified from an Arabidopsis thaliana cDNA library, cloned in a purpose-built fungal multigene expression vector and expressed in Aspergillus oryzae. HPLC-MS analysis of the transgenic fungus homogenate gave good evidence for the presence of 3-oxo-2-(2'-pentenyl)-cyclopentane-1-octanoic acid.

Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent

NARCIS (Netherlands)

Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Martini, I A; Muskiet, F A

Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and

Engaging the Terminal: Promoting Halogen Bonding Interactions with Uranyl Oxo Atoms.

Science.gov (United States)

Carter, Korey P; Kalaj, Mark; Surbella, Robert G; Ducati, Lucas C; Autschbach, Jochen; Cahill, Christopher L

2017-11-02

Engaging the nominally terminal oxo atoms of the linear uranyl (UO 2 2+ ) cation in non-covalent interactions represents both a significant challenge and opportunity within the field of actinide hybrid materials. An approach has been developed for promoting oxo atom participation in a range of non-covalent interactions, through judicious choice of electron donating equatorial ligands and appropriately polarizable halogen-donor atoms. As such, a family of uranyl hybrid materials was generated based on a combination of 2,5-dihalobenzoic acid and aromatic, chelating N-donor ligands. Delineation of criteria for oxo participation in halogen bonding interactions has been achieved by preparing materials containing 2,5-dichloro- (25diClBA) and 2,5-dibromobenzoic acid (25diBrBA) coupled with 2,2'-bipyridine (bipy) (1 and 2), 1,10-phenanthroline (phen) (3-5), 2,2':6',2''-terpyridine (terpy) (6-8), or 4'-chloro-2,2':6',2''-terpyridine (Cl-terpy) (9-10), which have been characterized through single crystal X-ray diffraction, Raman, Infrared (IR), and luminescence spectroscopy, as well as through density functional calculations of electrostatic potentials. Looking comprehensively, these results are compared with recently published analogues featuring 2,5-diiodobenzoic acid which indicate that although inclusion of a capping ligand in the uranyl first coordination sphere is important, it is the polarizability of the selected halogen atom that ultimately drives halogen bonding interactions with the uranyl oxo atoms. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

Directory of Open Access Journals (Sweden)

Hiroshi Honda

Full Text Available The alpha-linolenic acid (ALA-diacylglycerol (DAG oil is an edible oil enriched with DAG (>80% and ALA (>50%. Although DAG oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of DAG. Therefore, the purpose of this study was to evaluate the genotoxicity of ALA-DAG oil using standard genotoxicity tests in accordance with the OECD guidelines. ALA-DAG oil showed negative results in the bacterial reverse mutation test (Ames test and in vitro micronucleus test in cultured Chinese hamster lung cells with and without metabolic activation, and in the in vivo bone marrow micronucleus test in mice. Our results did not show any genotoxicity, suggesting that the fatty acid composition had no deleterious effects. We conclude that ALA-DAG oil had no genotoxicity concerns under the testing conditions. Keywords: Alpha-linolenic acid-rich diacylglycerol, Diacylglycerol, Alpha-linolenic acid, Fatty acid composition, Genotoxicity

Detailed dimethylacetal and fatty acid composition of rumen content from lambs fed lucerne or concentrate supplemented with soybean oil.

Science.gov (United States)

Alves, Susana P; Santos-Silva, José; Cabrita, Ana R J; Fonseca, António J M; Bessa, Rui J B

2013-01-01

Lipid metabolism in the rumen is responsible for the complex fatty acid profile of rumen outflow compared with the dietary fatty acid composition, contributing to the lipid profile of ruminant products. A method for the detailed dimethylacetal and fatty acid analysis of rumen contents was developed and applied to rumen content collected from lambs fed lucerne or concentrate based diets supplemented with soybean oil. The methodological approach developed consisted on a basic/acid direct transesterification followed by thin-layer chromatography to isolate fatty acid methyl esters from dimethylacetal, oxo- fatty acid and fatty acid dimethylesters. The dimethylacetal composition was quite similar to the fatty acid composition, presenting even-, odd- and branched-chain structures. Total and individual odd- and branched-chain dimethylacetals were mostly affected by basal diet. The presence of 18:1 dimethylacetals indicates that biohydrogenation intermediates might be incorporated in structural microbial lipids. Moreover, medium-chain fatty acid dimethylesters were identified for the first time in the rumen content despite their concentration being relatively low. The fatty acids containing 18 carbon-chain lengths comprise the majority of the fatty acids present in the rumen content, most of them being biohydrogenation intermediates of 18:2n-6 and 18:3n-3. Additionally, three oxo- fatty acids were identified in rumen samples, and 16-O-18:0 might be produced during biohydrogenation of the 18:3n-3.

Red-excitation resonance Raman analysis of the nu(Fe=O) mode of ferryl-oxo hemoproteins.

Science.gov (United States)

Ikemura, Kenichiro; Mukai, Masahiro; Shimada, Hideo; Tsukihara, Tomitake; Yamaguchi, Satoru; Shinzawa-Itoh, Kyoko; Yoshikawa, Shinya; Ogura, Takashi

2008-11-05

The Raman excitation profile of the nuFe O mode of horseradish peroxidase compound II exhibits a maximum at 580 nm. This maximum is located within an absorption band with a shoulder assignable to an oxygen-to-iron charge transfer band on the longer wavelength side of the alpha-band. Resonance Raman bands of the nuFe O mode of various ferryl-oxo type hemoproteins measured at 590 nm excitation indicate that many hemoproteins in the ferryl-oxo state have an oxygen-to-iron charge transfer band in the visible region. Since this red-excited resonance Raman technique causes much less photochemical damage in the proteins relative to blue-excited resonance Raman spectroscopy, it produces a higher signal-to-noise ratio and thus represents a powerful tool for investigations of ferryl-oxo intermediates of hemoproteins.

New insights into thorium and uranium oxo-arsenic (III/V) and oxo-phosphates (V) crystal chemistry

International Nuclear Information System (INIS)

Yu, Na

2015-01-01

The fundamental chemistry of actinides is of great interest owing to the diverse number of valence states and complex coordination chemistry of the actinides. The phases based on actinides and oxo-salt fragments have been under thorough investigation in the last decades. These compounds can be widely found in nature and they affect the migration process of actinides in nature. A better understanding of the fundamental coordination chemistry of actinide compounds with oxo-salts of group V elements is not only important for understanding the actinides behavior within the migration process but can also be used to understand actinide properties in phosphate ceramics. Concerning the radioactive issues, the less radioactive early actinides (i.e. U, Th) can be taken as modeling elements to study the crystal chemistry of the transuranic elements (Np, Pu) without the major handling problems. This can be done as Th(IV) has a very similar coordination chemistry with An(IV) and U(VI) can be chosen as a modeling element for transuranic elements in higher valence states. Therefore, a systematic research on the actinides (U, Th) bearing phases with tetrahedral oxo-anions such as phosphates and arsenates have been performed in this work. High temperature (HT) solid state reaction, High pressure high temperature (HP-HT) solid state reaction and the hydrothermal method were the methods of choice for synthesizing actinide bearing oxo-arsenic(III/V) and oxo- phosphorus(V) phases in the past three years. As a result, numerous novel compounds containing actinides were obtained. The structures of all compounds were determined using single crystal X-ray diffraction data. Raman spectroscopy, EDS, DSC and high temperature powder X-ray diffraction (HT-PXRD) measurements were implemented to characterize the chemical and physical properties of the obtained compounds. The core of this dissertation is a fundamental study of the crystal chemistry of actinides (Th, U) oxo-arsenic (III/V) and oxo

Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

Science.gov (United States)

Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

2007-01-01

Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

DEFF Research Database (Denmark)

Teisner, B; Rasmussen, H B; Højrup, P

1992-01-01

-PAGE analysis gave an M(r) = 27 kDa under reducing and non-reducing conditions for both forms, whereas the exact M(r) determined by mass spectrometry was 14,343 +/- 3 Da. FA2 was N-terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity...... with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans. Udgivelsesdato: 1992-Dec...

Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid.

Science.gov (United States)

Lu, Yingnian; Wu, Kefeng; Li, Li; He, Yuhui; Cui, Liao; Liang, Nianci; Mu, Bozhong

2013-01-01

The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (henceforth referred to as 5F), to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG)-400 (2:1, w/w). The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route.

New insights into thorium and uranium oxo-arsenic (III/V) and oxo-phosphates (V) crystal chemistry

Energy Technology Data Exchange (ETDEWEB)

Yu, Na

2015-12-11

The fundamental chemistry of actinides is of great interest owing to the diverse number of valence states and complex coordination chemistry of the actinides. The phases based on actinides and oxo-salt fragments have been under thorough investigation in the last decades. These compounds can be widely found in nature and they affect the migration process of actinides in nature. A better understanding of the fundamental coordination chemistry of actinide compounds with oxo-salts of group V elements is not only important for understanding the actinides behavior within the migration process but can also be used to understand actinide properties in phosphate ceramics. Concerning the radioactive issues, the less radioactive early actinides (i.e. U, Th) can be taken as modeling elements to study the crystal chemistry of the transuranic elements (Np, Pu) without the major handling problems. This can be done as Th(IV) has a very similar coordination chemistry with An(IV) and U(VI) can be chosen as a modeling element for transuranic elements in higher valence states. Therefore, a systematic research on the actinides (U, Th) bearing phases with tetrahedral oxo-anions such as phosphates and arsenates have been performed in this work. High temperature (HT) solid state reaction, High pressure high temperature (HP-HT) solid state reaction and the hydrothermal method were the methods of choice for synthesizing actinide bearing oxo-arsenic(III/V) and oxo- phosphorus(V) phases in the past three years. As a result, numerous novel compounds containing actinides were obtained. The structures of all compounds were determined using single crystal X-ray diffraction data. Raman spectroscopy, EDS, DSC and high temperature powder X-ray diffraction (HT-PXRD) measurements were implemented to characterize the chemical and physical properties of the obtained compounds. The core of this dissertation is a fundamental study of the crystal chemistry of actinides (Th, U) oxo-arsenic (III/V) and oxo

Dimerization of A-[alpha]-[SiNb3W9O40]7- by pH-controlled formation of individual Nb−µ-O−Nb linkages

Science.gov (United States)

Gyu-Shik Kim; Huadong Zeng; Wade A. Neiwert; Jennifer J. Cowan; Donald VanDerveer; Craig L. Hill; Ira A. Weinstock

2003-01-01

The reversible, stepwise formation of individual Nb−µ-O−Nb linkages during acid condensation of 2 equiv of A-[alpha]-[SiNb3W9O40]7- (1) to the tri-µ-oxo-bridged structure A-[alpha]-[Si2Nb6W18O77]8- (4) is demonstrated by a combination of X-ray crystallography and variable-pD solution 183W and 29Si NMR spectroscopy. Addition of DCl to a pD 8.4...

Biotransformation of cannabidiol in mice. Identification of new acid metabolites.

Science.gov (United States)

Martin, B R; Harvey, D J; Paton, W D

1977-01-01

The in vivo metabolism of cannabidiol (CBD) was investigated in mice. Following the ip administration of CBD to mice, livers were removed and metabolites were extracted with ethyl acetate prior to partial purification on Sephadex LH-20 columns. Fractions from the columns were converted into trimethylsilyl, d9-trimethylsilyl, and methylester-trimethylsilyl derivatives for analysis by gas-liquid chromatography-mass spectrometry. In addition, metabolites containing carboxylic acid and ketone functional groups were reduced to alcohols with lithium aluminum deuteride before trimethylsilation. A total of 22 metabolites were characterized, 14 of which had not been reported previously. The metabolites could be categorized as follows: monohydroxylated (N=2), dihydroxylated (N=3), CBD-7-oic acid, side chain hydroxy-GBD-7-oic acids (N=3), side-chain acids (N=3), 7-hydroxy-side-chain acids (N=4), 6-oxo-side-chain acids (N=3) and glucuronide conjugates (N=3). The most significant biotransformations were glucuronide conjugation and, to a lesser extent, formation of CBD-7-oic acid.

A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids

OpenAIRE

Zheng, Xiaojiao; Qiu, Yunping; Zhong, Wei; Baxter, Sarah; Su, Mingming; Li, Qiong; Xie, Guoxiang; Ore, Brandon M.; Qiao, Shanlei; Spencer, Melanie D.; Zeisel, Steven H.; Zhou, Zhanxiang; Zhao, Aihua; Jia, Wei

2013-01-01

Research in obesity and metabolic disorders that involve intestinal microbiota demands reliable methods for the precise measurement of the short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) concentration. Here, we report a rapid method of simultaneously determining SCFAs and BCAAs in biological samples using propyl chloroformate (PCF) derivatization followed by gas chromatography mass spectrometry (GC-MS) analysis. A one-step derivatization using 100 µL of PCF in a reactio...

Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells.

Science.gov (United States)

Lu, Gang; Sun, Haipeng; She, Pengxiang; Youn, Ji-Youn; Warburton, Sarah; Ping, Peipei; Vondriska, Thomas M; Cai, Hua; Lynch, Christopher J; Wang, Yibin

2009-06-01

The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibition of the branched-chain-alpha-ketoacid dehydrogenase (BCKD) complex, the rate-limiting step in their metabolism. BCKD is inhibited by phosphorylation of its E1alpha subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates. Loss of PP2Cm completely abolished substrate-induced E1alpha dephosphorylation both in vitro and in vivo. PP2Cm-deficient mice exhibited BCAA catabolic defects and a metabolic phenotype similar to the intermittent or intermediate types of human maple syrup urine disease (MSUD), a hereditary disorder caused by defects in BCKD activity. These results indicate that PP2Cm is the endogenous BCKD phosphatase required for nutrient-mediated regulation of BCKD activity and suggest that defects in PP2Cm may be responsible for a subset of human MSUD.

A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia

International Nuclear Information System (INIS)

Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y.

1989-01-01

The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with [ 3 H]N-ethylmaleimide. This pool of soluble alpha chains was 0.067 ± 0.017% of hemoglobin in blood of normal adult, 0.11 ± 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using [ 3 H]N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress.

Science.gov (United States)

Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

2016-04-01

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. Copyright © 2016. Published by Elsevier Inc.

Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

Science.gov (United States)

Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

2001-05-01

The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

The synthesis of taurine-conjugated bile acids and bile acid sulfates labeled with {sup 14}C or {sup 3}H in the taurine moiety

Energy Technology Data Exchange (ETDEWEB)

Jie Zhang; Griffiths, W.J.; Sjoevall, Jan [Karolinska Inst., Medical Biochemistry and Biophysics Dept., Stockholm (Sweden)

1997-02-01

Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7{alpha}-hydroxy-3-oxo-{Delta}{sup 4} or 3{beta}, 7{alpha}-dihydroxy-{Delta}{sup 5} structures. Taurine labeled with {sup 14}C or {sup 3}H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with {sup 14}C- or {sup 3}H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%. (author).

40 CFR 180.1281 - S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6... Exemptions From Tolerances § 180.1281 S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2... from the requirement of a tolerance is established for residues of S-Abscisic Acid in or on all food...

Peptide design using alpha,beta-dehydro amino acids: from beta-turns to helical hairpins.

Science.gov (United States)

Mathur, Puniti; Ramakumar, S; Chauhan, V S

2004-01-01

Incorporation of alpha,beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded conformations: beta-turns in short peptides and 3(10)-helices in larger ones. A few exceptions-namely, alpha-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi) approximately (-60 degrees, -30 degrees ), (-60 degrees, 150 degrees ), (80 degrees, 0 degrees ) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing DeltaPhe zippers and helix-turn-helix motifs. DeltaPhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C--H.O==C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of multicentered interactions namely, a donor in aromatic C--H.pi and C--H.O==C and an acceptor in a CH(3).pi interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures. Copyright 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

Hydrogen/deuterium exchange of cross-linkable alpha-amino acid derivatives in deuterated triflic acid

OpenAIRE

Wang, Lei; Murai, Yuta; Yoshida, Takuma; Okamoto, Masashi; Masuda, Katsuyoshi; Sakihama, Yasuko; Hashidoko, Yasuyuki; Hatanaka, Yasumaru; Hashimoto, Makoto

2014-01-01

In this paper we report here a hydrogen/deuterium exchange (H/D exchange) of cross-linkable alpha-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD). H/D exchange with TfOD was easily applied to o-catechol containing phenylalanine (DOPA) within an hour. A partial H/D exchange was observed for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives. N-Acetyl-protected natural aromatic alpha-amino acids (Tyr and Trp) were more effective in H/D exchange than unprotect...

Branched-chain amino acids for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Koretz, R L; Kjaergard, L L

2003-01-01

Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be caused by a decreased plasma ratio of branched-chain amino acids (BCAA) to aromatic amino acids. Treatment with BCAA may therefore have a beneficial effect on patients with hepatic encephalopathy....

Primary structure of the hemoglobin beta-chain of rose-ringed parakeet (Psittacula krameri).

Science.gov (United States)

Islam, A; Persson, B; Zaidi, Z H; Jörnvall, H

1989-08-01

The primary structure of Rose-ringed Parakeet hemoglobin beta-chain was established, completing the analysis of this hemoglobin. Comparison with other avian beta-chains show variations smaller than those for the corresponding alpha-chains. There are 11 amino acid exchanges in relationship to the only other characterized psittaciform beta-chain, and a total of 35 positions are affected by differences among all avian beta-chains analyzed (versus 61 for the alpha-chains). At three positions, the Psittacula beta-chain has residues unique to this species. Three alpha 1 beta 1 contacts are modified, by substitutions at positions beta 51, beta 116, and beta 125.

Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

Energy Technology Data Exchange (ETDEWEB)

Kimura, Rino [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Murota, Kaeko [Department of Life Science, School of Science and Engineering, Kinki University, Osaka 770-8503 (Japan); Yamada, Yuko [Laboratory of Physiological Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Moriyama, Tatsuya [Department of Applied Cell Biology, Graduate School of Agriculture, Kinki University, Nara 631-8505 (Japan); Goto, Tsuyoshi; Kawada, Teruo [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

2011-06-24

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and

Human beta 2 chain of laminin (formerly S chain): cDNA cloning, chromosomal localization, and expression in carcinomas

DEFF Research Database (Denmark)

Wewer, U M; Gerecke, D R; Durkin, M E

1994-01-01

or other known laminin genes. Immunostaining showed that the beta 2 chain is localized to the smooth muscle basement membranes of the arteries, while the homologous beta 1 chain is confined to the subendothelial basement membranes. The beta 2 chain was found in the basement membranes of ovarian carcinomas......Overlapping cDNA clones that encode the full-length human laminin beta 2 chain, formerly called the S chain, were isolated. The cDNA of 5680 nt contains a 5391-nt open reading frame encoding 1797 amino acids. At the amino terminus is a 32-amino-acid signal peptide that is followed by the mature...... beta 2 chain polypeptide of 1765 amino acids with a calculated molecular mass of 192,389 Da. The human beta 2 chain is predicted to have all of the seven structural domains typical of the beta chains of laminin, including the short cysteine-rich alpha region. The amino acid sequence of human beta 2...

Synthesis of 1-Methyl-3-oxo-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic Acid Methyl Ester

Directory of Open Access Journals (Sweden)

Gil Valdo José da Silva

2005-11-01

Full Text Available A simple and efficient method for the preparation of 1-methyl-3-oxo-7- oxabicyclo[2.2.1]hept-5-en-2-carboxylic acid methyl ester (1 is described. The first step is a highly regioselective Diels-Alder reaction between 2-methylfuran and methyl-3-bromo- propiolate. A remarkably difficult ketal hydrolysis reaction was effected by treatment with HCl, a simple reagent that was shown to be more efficient, in this case, than commonly used more elaborate methods.

HB KURDISTAN [ALPHA-47(CE5)ASP-]TYR], A NEW ALPHA-CHAIN VARIANT IN COMBINATION WITH BETA-THALASSEMIA

NARCIS (Netherlands)

GIORDANO, PC; HARTEVELD, CL; STRENG, H; Oosterwijk, Jan; HEISTER, JGAM; AMONS, R; BERNINI, LF

1994-01-01

We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological investigation of eight individuals have shown that the a variant is associated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map

Molecular Basis of Prodrug Activation by Human Valacyclovirase, an [alpha]-Amino Acid Ester Hydrolase

Energy Technology Data Exchange (ETDEWEB)

Lai, Longsheng; Xu, Zhaohui; Zhou, Jiahai; Lee, Kyung-Dall; Amidon, Gordon L. (Michigan)

2008-07-08

Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of {alpha}-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific {alpha}-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.

Axolotl hemoglobin: cDNA-derived amino acid sequences of two alpha globins and a beta globin from an adult Ambystoma mexicanum.

Science.gov (United States)

Shishikura, Fumio; Takeuchi, Hiro-aki; Nagai, Takatoshi

2005-11-01

Erythrocytes of the adult axolotl, Ambystoma mexicanum, have multiple hemoglobins. We separated and purified two kinds of hemoglobin, termed major hemoglobin (Hb M) and minor hemoglobin (Hb m), from a five-year-old male by hydrophobic interaction column chromatography on Alkyl Superose. The hemoglobins have two distinct alpha type globin polypeptides (alphaM and alpham) and a common beta globin polypeptide, all of which were purified in FPLC on a reversed-phase column after S-pyridylethylation. The complete amino acid sequences of the three globin chains were determined separately using nucleotide sequencing with the assistance of protein sequencing. The mature globin molecules were composed of 141 amino acid residues for alphaM globin, 143 for alpham globin and 146 for beta globin. Comparing primary structures of the five kinds of axolotl globins, including two previously established alpha type globins from the same species, with other known globins of amphibians and representatives of other vertebrates, we constructed phylogenetic trees for amphibian hemoglobins and tetrapod hemoglobins. The molecular trees indicated that alphaM, alpham, beta and the previously known alpha major globin were adult types of globins and the other known alpha globin was a larval type. The existence of two to four more globins in the axolotl erythrocyte is predicted.

Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

Energy Technology Data Exchange (ETDEWEB)

Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

2011-04-22

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

Heavy Chain Diseases

Science.gov (United States)

... of heavy chain produced: Alpha Gamma Mu Alpha Heavy Chain Disease Alpha heavy chain disease (IgA heavy ... the disease or lead to a remission. Gamma Heavy Chain Disease Gamma heavy chain disease (IgG heavy ...

Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.

Science.gov (United States)

Liang, T; Liao, S

1992-01-01

Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells. PMID:1637346

Improved zeolite regeneration processes for preparing saturated branched-chain fatty acids

Science.gov (United States)

Ferrierite zeolite solid is an excellent catalyst for the skeletal isomerization of unsaturated linear-chain fatty acids (i.e., oleic acid) to unsaturated branched-chain fatty acids (i.e., iso-oleic acid) follow by hydrogenation to give saturated branched-chain fatty acids (i.e., isostearic acid). ...

Towards control of aggregational behaviour of alpha-lactalbumin at acidic pH.

Science.gov (United States)

Pedersen, Jane B; Fojan, Peter; Sorensen, John; Petersen, Steffen B

2006-07-01

alpha-Lactalbumin (alpha-La) undergoes considerable structural changes upon loss of bound Ca2+ at acidic pH, leaving alpha-La in a molten globule structure. Using fluorescence the present work provides more insight into the structural transition of alpha-La at acidic pH leading to protein aggregation, most likely caused by a combination of hydrophobic and electrostatic interactions. The rate of aggregation is determined by the protein concentration and temperature applied. Availability of Ca2+ stabilises the protein, and thus prevent aggregation at pH values as low as pH 2.9. In contrast, presence of Cu2+ induces a destabilisation of the protein, which can be explained by a binding to the Zn2+ binding site in alpha-La, possibly resulting in structural alterations of the protein. In general, presence of anions destabilize alpha-La at pH values below pI, with SO4(2-) exhibiting the strongest effect on the protein stability, thus correlating well with the Hofmeister series. At more acidic pH values far from pI, alpha-La becomes more stable towards ion induced aggregation, since higher ion activity is required to efficiently screen the charges on the protein surface. The results presented in this paper provide detailed knowledge on the external parameters leading to aggregation of alpha-La at acidic pH, thus permitting rational design of the aggregation process.

Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes.

Directory of Open Access Journals (Sweden)

Scott B Crown

Full Text Available The branched chain amino acids (BCAA valine, leucine and isoleucine have been implicated in a number of diseases including obesity, insulin resistance, and type 2 diabetes mellitus, although the mechanisms are still poorly understood. Adipose tissue plays an important role in BCAA homeostasis by actively metabolizing circulating BCAA. In this work, we have investigated the link between BCAA catabolism and fatty acid synthesis in 3T3-L1 adipocytes using parallel 13C-labeling experiments, mass spectrometry and model-based isotopomer data analysis. Specifically, we performed parallel labeling experiments with four fully 13C-labeled tracers, [U-13C]valine, [U-13C]leucine, [U-13C]isoleucine and [U-13C]glutamine. We measured mass isotopomer distributions of fatty acids and intracellular metabolites by GC-MS and analyzed the data using the isotopomer spectral analysis (ISA framework. We demonstrate that 3T3-L1 adipocytes accumulate significant amounts of even chain length (C14:0, C16:0 and C18:0 and odd chain length (C15:0 and C17:0 fatty acids under standard cell culture conditions. Using a novel GC-MS method, we demonstrate that propionyl-CoA acts as the primer on fatty acid synthase for the production of odd chain fatty acids. BCAA contributed significantly to the production of all fatty acids. Leucine and isoleucine contributed at least 25% to lipogenic acetyl-CoA pool, and valine and isoleucine contributed 100% to lipogenic propionyl-CoA pool. Our results further suggest that low activity of methylmalonyl-CoA mutase and mass action kinetics of propionyl-CoA on fatty acid synthase result in high rates of odd chain fatty acid synthesis in 3T3-L1 cells. Overall, this work provides important new insights into the connection between BCAA catabolism and fatty acid synthesis in adipocytes and underscores the high capacity of adipocytes for metabolizing BCAA.

Stereospecific enzymatic transformation of alpha-ketoglutarate to (2S,3R)-3-methyl glutamate during acidic lipopeptide biosynthesis.

Science.gov (United States)

Mahlert, Christoph; Kopp, Florian; Thirlway, Jenny; Micklefield, Jason; Marahiel, Mohamed A

2007-10-03

The acidic lipopeptides, including the calcium-dependent antibiotics (CDA), daptomycin, and A54145, are important macrocyclic peptide natural products produced by Streptomyces species. All three compounds contain a 3-methyl glutamate (3-MeGlu) as the penultimate C-terminal residue, which is important for bioactivity. Here, biochemical in vitro reconstitution of the 3-MeGlu biosynthetic pathway is presented, using exclusively enzymes from the CDA producer Streptomyces coelicolor. It is shown that the predicted 3-MeGlu methyltransferase GlmT and its homologues DptI from the daptomycin producer Streptomyces roseosporus and LptI from the A54145 producer Streptomyces fradiae do not methylate free glutamic acid, PCP-bound glutamate, or Glu-containing CDA in vitro. Instead, GlmT, DptI, and LptI are S-adenosyl methionine (SAM)-dependent alpha-ketoglutarate methyltransferases that catalyze the stereospecific methylation of alpha-ketoglutarate (alphaKG) leading to (3R)-3-methyl-2-oxoglutarate. Subsequent enzyme screening identified the branched chain amino acid transaminase IlvE (SCO5523) as an efficient catalyst for the transformation of (3R)-3-methyl-2-oxoglutarate into (2S,3R)-3-MeGlu. Comparison of reversed-phase HPLC retention time of dabsylated 3-MeGlu generated by the coupled enzymatic reaction with dabsylated synthetic standards confirmed complete stereocontrol during enzymatic catalysis. This stereospecific two-step conversion of alphaKG to (2S,3R)-3-MeGlu completes our understanding of the biosynthesis and incorporation of beta-methylated amino acids into the nonribosomal lipopeptides. Finally, understanding this pathway may provide new possibilities for the production of modified peptides in engineered microbes.

Diving behaviour and haemoglobin function: the primary structure of the alpha- and beta-chains of the sea turtle (Caretta caretta) and its functional implications.

Science.gov (United States)

Petruzzelli, R; Aureli, G; Lania, A; Galtieri, A; Desideri, A; Giardina, B

1996-06-15

The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

Palladium-Catalyzed alpha-Arylation of Tetramic Acids

DEFF Research Database (Denmark)

Storgaard, Morten; Dorwald, F. Z.; Peschke, B.

2009-01-01

A mild, racemization-free, palladium-Catalyzed alpha-arylation of tetramic acids (2,4-pyrrolidinediones) has been developed. Various amino acid-derived tetramic acids were cleanly arylated by treatment with 2 mol % of Pd(OAc)(2), 4 mol % of a sterically demanding biaryl phosphine, 2.3 equiv of K2CO...... no effect on their reactivity: both electron-rich and electron-poor aryl chlorides and bromides or triflates led to good yields. Ortho-substituted aryl halides and heteroaryl halides, however, did not undergo the title reaction....

Side Chain Cyclized Aromatic Amino Acids

DEFF Research Database (Denmark)

Van der Poorten, Olivier; Knuhtsen, Astrid; Sejer Pedersen, Daniel

2016-01-01

Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute...... the peptide pharmacophore is equally important. Control of χ-space utilizes conformationally constrained amino acids that favor, disfavor, or exclude the gauche (-), the gauche (+), or the trans conformation. In this review we focus on cyclic aromatic amino acids in which the side chain is connected...... to the peptide backbone to provide control of χ(1)- and χ(2)-space. The manifold applications for cyclized analogues of the aromatic amino acids Phe, Tyr, Trp, and His within peptide medicinal chemistry are showcased herein with examples of enzyme inhibitors and ligands for G protein-coupled receptors....

PROCESS FOR HYDROGENOLYSIS OF ALPHA-HYDROXY ESTERS OR ACIDS USING A HETEROGENEOUS CATALYST

DEFF Research Database (Denmark)

2017-01-01

The present invention relates to a method for hydrogenolysis of alpha-hydroxy esters or acids, comprising reacting the alpha-hydroxy ester or acid in the presence of a heterogeneous catalyst. The present invention also relates to a method for producing propionic acid ester, and the use of any...

Importance of medium chain fatty acids in animal nutrition

Science.gov (United States)

Baltić, B.; Starčević, M.; Đorđević, J.; Mrdović, B.; Marković, R.

2017-09-01

Fats in animal and human nutrition are a common subject of research. These studies most often pay attention to particular fat groups (saturated, unsaturated, polyunsaturated fats or fats grouped by the length of their fatty acid chains into short, medium or long chain fatty acids). Medium chain fatty acids (MCFAs) have two main sources: milk and coconut oil. To date, research has shown these acids have positive effects on health, production, feed digestibility and lower body and muscle fats in broilers and swine. MCFAs possess antibacterial, anticoccidial and antiviral effects. Also, it has been proven that these acids act synergistically if they are used together with organic acids, essential oils, or probiotics. Nowadays, commercial MCFA products are available for use in animal nutrition as feed additives.

Attachment of di- and tricarboxylic acids to the starting structure of kukersite kerogen

Energy Technology Data Exchange (ETDEWEB)

Pobul, L; Mannik, A

1974-01-01

Oxidation of the kerogen of kukersite by alkaline permanganate at 50/sup 0/C gave a product containing straight-chain dicarboxylic acids (up to 80%), among which C/sub 4/-C/sub 10/ acids predominated (over 70%). Tricarboxylic acids (15 to 20%) and ..cap alpha..-methyl dicarboxylic acids (4 to 10%) were present. Straight-chain monocarboxylic acids, their isomers, and phenyl derivatives contributed less than 1%. Probably, ..cap alpha..-methyl dicarboxylic and tricarboxylic acids were original structural units of the kerogen. Similar oxidations of Baltic shale indicated that kerogens of different combustible shales differ in chemical composition, but the content of polymers of fatty acids was characteristic. Oxidation of the polymeric acids gave straight-chain mono- and dicarboxylic acids.

Synthesis, screening and QSAR studies of 3-benzoyl-2-oxo/thioxo-1 ...

African Journals Online (AJOL)

5-Acyl-6-methyl-4-substituted-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidines (A) were synthesized by cyclocondensation reaction between appropriate aldehyde, acetoacetate and urea/thiourea in presence of aluminium chloride and hydrochloric acid which upon treatment with benzoyl chloride in presence of pyridine in ...

Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria.

Science.gov (United States)

Doden, Heidi; Sallam, Lina A; Devendran, Saravanan; Ly, Lindsey; Doden, Greta; Daniel, Steven L; Alves, João M P; Ridlon, Jason M

2018-05-15

Bile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacterium Clostridium leptum ; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such as Clostridium scindens , Clostridium hylemonae , and Clostridium hiranonis Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread among Firmicutes , Actinobacteria in the Coriobacteriaceae family, and human gut Archaea IMPORTANCE 12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteria C. scindens , C. hiranonis , and C. hylemonae Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In

Topochemical approach to efficiently produce main-chain poly(bile acid)s with high molecular weights.

Science.gov (United States)

Li, Weina; Li, Xuesong; Zhu, Wei; Li, Changxu; Xu, Dan; Ju, Yong; Li, Guangtao

2011-07-21

Based on a topochemical approach, a strategy for efficiently producing main-chain poly(bile acid)s in the solid state was developed. This strategy allows for facile and scalable synthesis of main-chain poly(bile acid)s not only with high molecular weights, but also with quantitative conversions and yields.

Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid

Directory of Open Access Journals (Sweden)

Lu Y

2013-05-01

Full Text Available Yingnian Lu,1,2 Kefeng Wu,2 Li Li,2 Yuhui He,2 Liao Cui,2 Nianci Liang,2 Bozhong Mu11Department of Chemistry, East China University of Science and Technology, Shanghai, 2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang, People’s Republic of ChinaAbstract: The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11a-hydroxy-15-oxo-kaur-16-en-19-oic- acid (henceforth referred to as 5F, to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG-400 (2:1, w/w. The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route.Keywords: antitumor, diterpenoid, microemulsion, pharmacokinetics, toxicity

Enantioselective synthesis of alpha,beta-disubstituted-beta-amino acids.

Science.gov (United States)

Sibi, Mukund P; Prabagaran, Narayanasamy; Ghorpade, Sandeep G; Jasperse, Craig P

2003-10-01

Highly diastereoselective and enantioselective addition of N-benzylhydroxylamine to imides 17 and 20-30 produces alpha,beta-trans-disubstituted N-benzylisoxazolidinones 19 and 31-41. These reactions proceed in 60-96% ee with 93-99% de's using 5 mol % of Mg(NTf2)2 and ligand 18. The product isoxazolidinones can be hydrogenolyzed directly to provide alpha,beta-disubstituted-beta-amino acids.

12-Oxo-Phytodienoic Acid Accumulation during Seed Development Represses Seed Germination in Arabidopsis[C][W][OA

Science.gov (United States)

Dave, Anuja; Hernández, M. Luisa; He, Zhesi; Andriotis, Vasilios M.E.; Vaistij, Fabián E.; Larson, Tony R.; Graham, Ian A.

2011-01-01

Arabidopsis thaliana COMATOSE (CTS) encodes an ABC transporter involved in peroxisomal import of substrates for β-oxidation. Various cts alleles and mutants disrupted in steps of peroxisomal β-oxidation have previously been reported to exhibit a severe block on seed germination. Oxylipin analysis on cts, acyl CoA oxidase1 acyl CoA oxidase2 (acx1 acx2), and keto acyl thiolase2 dry seeds revealed that they contain elevated levels of 12-oxo-phytodienoic acid (OPDA), jasmonic acid (JA), and JA-Ile. Oxylipin and transcriptomic analysis showed that accumulation of these oxylipins occurs during late seed maturation in cts. Analysis of double mutants generated by crossing cts with mutants in the JA biosynthesis pathway indicate that OPDA, rather than JA or JA-Ile, contributes to the block on germination in cts seeds. We found that OPDA was more effective at inhibiting wild-type germination than was JA and that this effect was independent of CORONATINE INSENSITIVE1 but was synergistic with abscisic acid (ABA). Consistent with this, OPDA treatment increased ABA INSENSITIVE5 protein abundance in a manner that parallels the inhibitory effect of OPDA and OPDA+ABA on seed germination. These results demonstrate that OPDA acts along with ABA to regulate seed germination in Arabidopsis. PMID:21335376

Catabolism of leucine to branched-chain fatty acids in Staphylococcus xylosus

DEFF Research Database (Denmark)

Beck, Hans Christian; Hansen, A M; Lauritsen, F R

2004-01-01

Staphylococcus xylosus is an important starter culture in the production of flavours from the branched-chain amino acids leucine, valine and isoleucine in fermented meat products. The sensorially most important flavour compounds are the branched-chain aldehydes and acids derived from the correspo......Staphylococcus xylosus is an important starter culture in the production of flavours from the branched-chain amino acids leucine, valine and isoleucine in fermented meat products. The sensorially most important flavour compounds are the branched-chain aldehydes and acids derived from...

Phytanic acid alpha-oxidation: decarboxylation of 2-hydroxyphytanoyl-CoA to pristanic acid in human liver

NARCIS (Netherlands)

Verhoeven, N. M.; Wanders, R. J.; Schor, D. S.; Jansen, G. A.; Jakobs, C.

1997-01-01

The degradation of the first intermediate in the alpha-oxidation of phytanic acid, 2-hydroxyphytanoyl-CoA, was investigated. Human liver homogenates were incubated with 2-hydroxyphytanoyl-CoA or 2-hydroxyphytanic acid, after which formation of 2-ketophytanic acid and pristanic acid were studied.

A Catalase-related Hemoprotein in Coral Is Specialized for Synthesis of Short-chain Aldehydes

Science.gov (United States)

Teder, Tarvi; Lõhelaid, Helike; Boeglin, William E.; Calcutt, Wade M.; Brash, Alan R.; Samel, Nigulas

2015-01-01

In corals a catalase-lipoxygenase fusion protein transforms arachidonic acid to the allene oxide 8R,9-epoxy-5,9,11,14-eicosatetraenoic acid from which arise cyclopentenones such as the prostanoid-related clavulones. Recently we cloned two catalase-lipoxygenase fusion protein genes (a and b) from the coral Capnella imbricata, form a being an allene oxide synthase and form b giving uncharacterized polar products (Lõhelaid, H., Teder, T., Tõldsepp, K., Ekins, M., and Samel, N. (2014) PloS ONE 9, e89215). Here, using HPLC-UV, LC-MS, and NMR methods, we identify a novel activity of fusion protein b, establishing its role in cleaving the lipoxygenase product 8R-hydroperoxy-eicosatetraenoic acid into the short-chain aldehydes (5Z)-8-oxo-octenoic acid and (3Z,6Z)-dodecadienal; these primary products readily isomerize in an aqueous medium to the corresponding 6E- and 2E,6Z derivatives. This type of enzymatic cleavage, splitting the carbon chain within the conjugated diene of the hydroperoxide substrate, is known only in plant cytochrome P450 hydroperoxide lyases. In mechanistic studies using 18O-labeled substrate and incubations in H218O, we established synthesis of the C8-oxo acid and C12 aldehyde with the retention of the hydroperoxy oxygens, consistent with synthesis of a short-lived hemiacetal intermediate that breaks down spontaneously into the two aldehydes. Taken together with our initial studies indicating differing gene regulation of the allene oxide synthase and the newly identified catalase-related hydroperoxide lyase and given the role of aldehydes in plant defense, this work uncovers a potential pathway in coral stress signaling and a novel enzymatic activity in the animal kingdom. PMID:26100625

BstXI RFLP in the human inter-alpha-trypsin inhibitor light chain gene

Energy Technology Data Exchange (ETDEWEB)

Leveillard, T; Bourguignon, J; Sesbouee, R; Hanauer, A; Salier, J P; Diarra-Mehrpour, M; Martin, J P

1988-03-25

The 1.2 kb EcoRI/SmaI fragment of lambdaHuLITI2 was used as probe. lambdaHuLITI2 is a full length cDNA clone coding for human inter-alpha-trypsin inhibitor light chain isolated from immunochemical screening of a lambdagt11 library. Its sequence coding for HI-30 and alpha-1-microglobulin is in agreement. BstXI identifies five invariant bands at 5.0 kb, 2.3 kb, 1.5 kb, 1.1 kb, and 0.7 kb and a diallelic polymorphism with DNA fragments at 2.0 kb or 1.7 kb.

Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids.

Science.gov (United States)

Annavarapu, Srinivas; Nanda, Vikas

2009-09-22

Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Propensities for amino acids to occur in contiguous alpha(L) helices correlate with published thermodynamic scales for incorporation of D-amino acids into alpha(R) helices. Two backbone rules for terminating a left-handed helix are found: an alpha(R) conformation is disfavored at the amino terminus, and a beta(R) conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to alpha(L) helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. By examining left-handed alpha-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed alpha-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds.

Inhibition of gastrin-stimulated gastric acid secretion by medium-chain triglycerides and long-chain triglycerides in healthy young men.

NARCIS (Netherlands)

Maas, M.I.M.; Hopman, W.P.M.; Katan, M.B.; Jansen, J.B.M.J.

1996-01-01

Long-chain triglycerides inhibit gastric acid secretion, but the effect of medium-chain triglycerides in humans is unknown. We compared the effects of intraduodenally perfused saline, medium-chain and long-chain triglycerides on gastrin-stimulated gastric acid secretion and cholecystokinin release.

Studies of iso-alpha-acids : analysis, purification, and stability.

NARCIS (Netherlands)

Khatib, Alfi

2006-01-01

The female cones of hop (Humulus lupulus L.) are added to beer, providing taste and flavour and contributing to the stability of foam. The main constituents of hop related to these properties are generically known as alpha-acids. During the brewing process, these acids are isomerized, resulting in

Mixed micelles of 7,12-dioxolithocholic acid and selected hydrophobic bile acids: interaction parameter, partition coefficient of nitrazepam and mixed micelles haemolytic potential.

Science.gov (United States)

Poša, Mihalj; Tepavčević, Vesna

2011-09-01

The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative β values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential. Copyright © 2011 Elsevier B.V. All rights reserved.

Visualisation of abscisic acid and 12-oxo-phytodienoic acid in immature Phaseolus vulgaris L. seeds using desorption electrospray ionisation-imaging mass spectrometry

Science.gov (United States)

Enomoto, Hirofumi; Sensu, Takuya; Sato, Kei; Sato, Futoshi; Paxton, Thanai; Yumoto, Emi; Miyamoto, Koji; Asahina, Masashi; Yokota, Takao; Yamane, Hisakazu

2017-02-01

The plant hormone abscisic acid (ABA) and the jasmonic acid related-compound 12-oxo-phytodienoic acid (OPDA) play crucial roles in seed development, dormancy, and germination. However, a lack of suitable techniques for visualising plant hormones has restricted the investigation of their biological mechanisms. In the present study, desorption electrospray ionisation-imaging mass spectrometry (DESI-IMS), a powerful tool for visualising metabolites in biological tissues, was used to visualise ABA and OPDA in immature Phaseolus vulgaris L. seed sections. The mass spectra, peak values and chemical formulae obtained from the analysis of seed sections were consistent with those determined for ABA and OPDA standards, as were the precursor and major fragment ions observed in tandem mass spectrometry (MS/MS) imaging. Furthermore, the precursor and fragment ion images showed similar distribution patterns. In addition, the localisation of ABA and OPDA using DESI-IMS was confirmed using liquid chromatography-MS/MS (LC-MS/MS). The results indicated that ABA was mainly distributed in the radical and cotyledon of the embryo, whereas OPDA was distributed exclusively in external structures, such as the hilum and seed coat. The present study is the first to report the visualisation of plant hormones using IMS, and demonstrates that DESI-IMS is a promising technique for future plant hormone research.

Electrochemically Generated cis-Carboxylato-Coordinated Iron(IV) Oxo Acid-Base Congeners as Promiscuous Oxidants of Water Pollutants

DEFF Research Database (Denmark)

de Sousa, David P; Miller, Christopher J; Chang, Yingyue

2017-01-01

The nonheme iron(IV) oxo complex [FeIV(O)(tpenaH)]2+ and its conjugate base [FeIV(O)(tpena)]+ [tpena- = N,N,N'-tris(2-pyridylmethyl)ethylenediamine-N'-acetate] have been prepared electrochemically in water by bulk electrolysis of solutions prepared from [FeIII2(μ-O)(tpenaH)2](ClO4)4 at potentials...... of the electrochemically generated iron(IV) oxo complexes, in terms of the broad range of substrates examined, represents an important step toward the goal of cost-effective electrocatalytic water purification....

Impact of Branched-Chain Amino Acid Catabolism on Fatty Acid and Alkene Biosynthesis in Micrococcus luteus.

Science.gov (United States)

Surger, Maximilian J; Angelov, Angel; Stier, Philipp; Übelacker, Maria; Liebl, Wolfgang

2018-01-01

Micrococcus luteus naturally produces alkenes, unsaturated aliphatic hydrocarbons, and represents a promising host to produce hydrocarbons as constituents of biofuels and lubricants. In this work, we identify the genes for key enzymes of the branched-chain amino acid catabolism in M. luteus , whose first metabolic steps lead also to the formation of primer molecules for branched-chain fatty acid and olefin biosynthesis, and demonstrate how these genes can be used to manipulate the production of specific olefins in this organism. We constructed mutants of several gene candidates involved in the branched-chain amino acid metabolism or its regulation and investigated the resulting changes in the cellular fatty acid and olefin profiles by GC/MS. The gene cluster encoding the components of the branched-chain α-keto acid dehydrogenase (BCKD) complex was identified by deletion and promoter exchange mutagenesis. Overexpression of the BCKD gene cluster resulted in about threefold increased olefin production whereas deletion of the cluster led to a drastic reduction in branched-chain fatty acid content and a complete loss of olefin production. The specificities of the acyl-CoA dehydrogenases of the branched amino acid degradation pathways were deduced from the fatty acid and olefin profiles of the respective deletion mutant strains. In addition, growth experiments with branched amino acids as the only nitrogen source were carried out with the mutants in order to confirm our annotations. Both the deletion mutant of the BCKD complex, responsible for the further degradation of all three branched-chain amino acids, as well as the deletion mutant of the proposed isovaleryl-CoA dehydrogenase (specific for leucine degradation) were not able to grow on leucine in contrast to the parental strain. In conclusion, our experiments allow the unambigous assignment of specific functions to the genes for key enzymes of the branched-chain amino acid metabolism of M. luteus . We also show how

The metabolism of phytanic acid and pristanic acid in man: a review

NARCIS (Netherlands)

Verhoeven, N. M.; Wanders, R. J.; Poll-The, B. T.; Saudubray, J. M.; Jakobs, C.

1998-01-01

The branched-chain fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this fatty acid in the human body is preceded by activation to phytanoyl-CoA and starts with one cycle of alpha-oxidation. Intermediates in this pathway are

Structural requirement of carboxyl-terminal globular domains of laminin alpha 3 chain for promotion of rapid cell adhesion and migration by laminin-5.

Science.gov (United States)

Hirosaki, T; Mizushima, H; Tsubota, Y; Moriyama, K; Miyazaki, K

2000-07-21

The basement membrane protein laminin-5, a heterotrimer of laminin alpha3, beta3, and gamma2 chains, potently promotes cellular adhesion and motility. It has been supposed that the carboxyl-terminal globular region of the alpha3 chain consisting of five distinct domains (G1 to G5) is important for its interaction with integrins. To clarify the function of each G domain, we transfected cDNAs for the full-length (wild type (WT)) and five deletion derivatives (DeltaGs) of the alpha3 chain into human fibrosarcoma cell line HT1080, which expressed and secreted the laminin beta3 and gamma2 chains but not the alpha3 chain. The transfectants with the alpha3 chain cDNAs lacking G5 (DeltaG(5)), G4-5 (DeltaG(4-5)), G3-5 (DeltaG(3-5)), and G2-5 (DeltaG(2-5)) secreted laminin-5 variants at levels comparable to that with WT cDNA. However, the transfectant with the cDNA without any G domains (DeltaG(1-5)) secreted little laminin-5, suggesting that the G domains are essential for the efficient assembly and secretion of the heterotrimer alpha3beta3gamma2. The transfectants with WT, DeltaG(5), and DeltaG(4-5) cDNAs survived in serum-free medium longer than those with DeltaG(3-5), DeltaG(2-5), and DeltaG(1-5) cDNAs. The transfectants with WT, DeltaG(5), and DeltaG(4-5) cDNAs secreted apparently the same size of laminin-5, which lacked G4 and G5 due to proteolytic cleavage between G3 and G4, and these laminin-5 forms potently promoted integrin alpha(3)beta(1)-dependent cell adhesion and migration. However, the laminin-5 forms of DeltaG(3-5) and DeltaG(2-5) hardly promoted the cell adhesion and motility. These findings demonstrate that the G3 domain, but not the G4 and G5 domains, of the alpha3 chain is essential for the potent promotion of cell adhesion and motility by laminin-5.

Inhibition of telomerase by linear-chain fatty acids: a structural analysis.

Science.gov (United States)

Oda, Masako; Ueno, Takamasa; Kasai, Nobuyuki; Takahashi, Hirotada; Yoshida, Hiromi; Sugawara, Fumio; Sakaguchi, Kengo; Hayashi, Hideya; Mizushina, Yoshiyuki

2002-01-01

In the present study, we have found that mono-unsaturated linear-chain fatty acids in the cis configuration with C(18) hydrocarbon chains (i.e. oleic acid) strongly inhibited the activity of human telomerase in a cell-free enzymic assay, with an IC(50) value of 8.6 microM. Interestingly, fatty acids with hydrocarbon chain lengths below 16 or above 20 carbons substantially decreased the potency of inhibition of telomerase. Moreover, the cis-mono-unsaturated C(18) linear-chain fatty acid oleic acid was the strongest inhibitor of all the fatty acids tested. A kinetic study revealed that oleic acid competitively inhibited the activity of telomerase ( K (i)=3.06 microM) with respect to the telomerase substrate primer. The energy-minimized three-dimensional structure of the linear-chain fatty acid was calculated and modelled. A molecule width of 11.53-14.26 A (where 1 A=0.1 nm) in the C(16) to C(20) fatty acid structure was suggested to be important for telomerase inhibition. The three-dimensional structure of the telomerase active site (i.e. the substrate primer-binding site) appears to have a pocket that could bind oleic acid, with the pocket being 8.50 A long and 12.80 A wide. PMID:12121150

Cis-12-oxo-phytodienoic acid stimulates rice defense response to a piercing-sucking insect.

Science.gov (United States)

Guo, Hui-Min; Li, Hai-Chao; Zhou, Shi-Rong; Xue, Hong-Wei; Miao, Xue-Xia

2014-11-01

The brown planthopper (BPH, Nilaparvata lugens) is a destructive, monophagous, piercing-sucking insect pest of rice. Previous studies indicated that jasmonic acid (JA) positively regulates rice defense against chewing insect pests but negatively regulates it against the piercing-sucking insect of BPH. We here demonstrated that overexpression of allene oxide cyclase (AOC) but not OPR3 (cis-12-oxo-phytodienoic acid (OPDA) reductase 3, an enzyme adjacent to AOC in the JA synthetic pathway) significantly increased rice resistance to BPH, mainly by reducing the feeding activity and survival rate. Further analysis revealed that plant response to BPH under AOC overexpression was independent of the JA pathway and that significantly higher OPDA levels stimulated rice resistance to BPH. Microarray analysis identified multiple candidate resistance-related genes under AOC overexpression. OPDA treatment stimulated the resistance of radish seedlings to green peach aphid Myzus persicae, another piercing-sucking insect. These results imply that rice resistance to chewing insects and to sucking insects can be enhanced simultaneously through AOC-mediated increases of JA and OPDA and provide direct evidence of the potential application of OPDA in stimulating plant defense responses to piercing-sucking insect pests in agriculture. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

Synthesis of 14C-labeled 3-{[1-ethoxycarbonyl-3-phenyl-(1S)-propyl]amino}-2,3,4,5-tetrahydro-2-oxo -1H-1-(3S)-benzazepine-1-acetic acid hydrochloride ([14C]CGS 14824A)

International Nuclear Information System (INIS)

Chaudhuri, N.K.; Patera, R.; Markus, B.; Mingsang Sung

1987-01-01

The title compound, CGS 14824A, was synthesized with a 14 C-label in the azepine ring in 14 steps starting with 1-bromo-3-phenylpropane (1) and K 14 CN in an overall yield of 1.31%. The reaction of 1 with K 14 CN yielded the nitrile 2 which upon hydrolysis followed by ring closure gave α-tetralone-1- 14 C (4). Bromination of 4 followed by oxime formation gave the bromo oxime 5, which upon Beckmann rearrangement by acid treatment yielded the ring expansion product 6. The bromine atom of 6 was then replaced by an azido group, and an acetic ester side chain was introduced at the nitrogen atom. Catalytic reduction of the azido compound 8 gave a mixture of epimeric amino esters which was resolved by salt formation with L-tartaric acid. The negatively rotating isomer was then reacted with 4-phenyl-2-oxo-butanoate in presence of sodium cyanoborohydride to give a mixture of diastereoisomers which were separated as their benzyl esters by chromatography. The major isomer was then converted to labeled CGS 14824A. (author)

Electron transport chains of lactic acid bacteria

NARCIS (Netherlands)

Brooijmans, R.J.W.

2008-01-01

Lactic acid bacteria are generally considered facultative anaerobic obligate fermentative bacteria. They are unable to synthesize heme. Some lactic acid bacteria are unable to form menaquinone as well. Both these components are cofactors of respiratory (electron transport) chains of prokaryotic

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program.

Science.gov (United States)

Silva, Marcilene Rezende; Sendin, Shimene Mascarenhas; Araujo, Isabela Couto de Oliveira; Pimentel, Fernanda Silva; Viana, Marcos Borato

2013-01-01

To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. β(S) allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. THE FOLLOWING ALPHA CHAIN VARIANTS WERE FOUND: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

VITAMIN C, VITAMIN A AND ALPHA HYDROXY ACID IN BENGKOANG (Pachyrhizus Erosus

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Ardian Widyatmoko

2016-04-01

Full Text Available Bengkoang or Pachyrhizus erosus has been used as a traditional cosmetic material since many years ago. Until now, many cosmetic preparations using bengkoang as a main material have been produced by cosmetic industries, mainly for skin care, whitening and sunscreen preparation. However, content of vitamin A, vitamin C and alpha hydroxyl acid has not been discovered yet. These compounds are essential in skin care process because of their activities in cell regeneration, antioxidant as well as peeling of dead skin cell layer. The aim of this research is to provide information about the content of three compounds in bengkoang. Vitamin A has been analysed by spectrophotometer, vitamin C analysed using titration method and alpha hydroxyl acid analysed using gas chromatography. The result showed that concentrations of vitamin A and vitamin C are 179.21 ± 8.19 ppm and 0.31 ± 0.06 %, respectively. Meanwhile the content of alpha hydroxyl acid was 0.80 ± 0.01% (measured as glycolic acid.

alpha-Crystallin A sequences of Alligator mississippiensis and the lizard Tupinambis teguixin: molecular evolution and reptilian phylogeny.

Science.gov (United States)

de Jong, W W; Zweers, A; Versteeg, M; Dessauer, H C; Goodman, M

1985-11-01

The amino acid sequences of the eye lens protein alpha-crystallin A from many mammalian and avian species, two frog species, and a dogfish have provided detailed information about the molecular evolution of this protein and allowed some useful inferences about phylogenetic relationships among these species. We now have isolated and sequenced the alpha-crystallins of the American alligator and the common tegu lizard. The reptilian alpha A chains appear to have evolved as slowly as those of other vertebrates, i.e., at two to three amino acid replacements per 100 residues in 100 Myr. The lack of charged replacements and the general types and distribution of replacements also are similar to those in other vertebrate alpha A chains. Maximum-parsimony analyses of the total data set of 67 vertebrate alpha A sequences support the monophyletic origin of alligator, tegu, and birds and favor the grouping of crocodilians and birds as surviving sister groups in the subclass Archosauria.

Medium-chain fatty acids undergo elongation before β-oxidation in fibroblasts

International Nuclear Information System (INIS)

Jones, Patricia M.; Butt, Yasmeen; Messmer, Bette; Boriak, Richard; Bennett, Michael J.

2006-01-01

Although mitochondrial fatty acid β-oxidation (FAO) is considered to be well understood, further elucidation of the pathway continues through evaluation of patients with FAO defects. The FAO pathway can be examined by measuring the 3-hydroxy-fatty acid (3-OHFA) intermediates. We present a unique finding in the study of this pathway: the addition of medium-chain fatty acids to the culture media of fibroblasts results in generation of 3-OHFAs which are two carbons longer than the precursor substrate. Cultured skin fibroblasts from normal and LCHAD-deficient individuals were grown in media supplemented with various chain-length fatty acids. The cell-free medium was analyzed for 3-OHFAs by stable-isotope dilution gas-chromatography/mass-spectrometry. Our finding suggests that a novel carbon chain-length elongation process precedes the oxidation of medium-chain fatty acids. This previously undescribed metabolic step may have important implications for the metabolism of medium-chain triglycerides, components in the dietary treatment of a number of disorders

Branched-Chain Amino Acids

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Matteo Ghiringhelli

2015-07-01

Full Text Available Our study is focused on evaluation and use of the most effective and correct nutrients. In particular, our attention is directed to the role of certain amino acids in cachectic patients. During parenteral nutrition in humans, physician already associates in the PN-bags different formulations including amino acids, lipids and glucose solutions or essential amino acids solution alone or exclusively branched-chain amino acids (BCAA. Studies investigated the effects of dietary BCAA ingestion on different diseases and conditions such as obesity and metabolic disorders, liver disease, muscle atrophy, cancer, impaired immunity or injuries (surgery, trauma, burns, and sepsis. BCAAs have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. Oral or parenteral administration of these three amino acids will allow us to evaluate the real efficacy of these compounds during a therapy to treat malnutrition in subjects unable to feed themselves.

Human carbonyl reductase 1 participating in intestinal first-pass drug metabolism is inhibited by fatty acids and acyl-CoAs.

Science.gov (United States)

Hara, Akira; Endo, Satoshi; Matsunaga, Toshiyuki; El-Kabbani, Ossama; Miura, Takeshi; Nishinaka, Toru; Terada, Tomoyuki

2017-08-15

Human carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily, reduces a variety of carbonyl compounds including endogenous isatin, prostaglandin E 2 and 4-oxo-2-nonenal. It is also a major non-cytochrome P450 enzyme in the phase I metabolism of carbonyl-containing drugs, and is highly expressed in the intestine. In this study, we found that long-chain fatty acids and their CoA ester derivatives inhibit CBR1. Among saturated fatty acids, myristic, palmitic and stearic acids were inhibitory, and stearic acid was the most potent (IC 50 9µM). Unsaturated fatty acids (oleic, elaidic, γ-linolenic and docosahexaenoic acids) and acyl-CoAs (palmitoyl-, stearoyl- and oleoyl-CoAs) were more potent inhibitors (IC 50 1.0-2.5µM), and showed high inhibitory selectivity to CBR1 over its isozyme CBR3 and other SDR superfamily enzymes (DCXR and DHRS4) with CBR activity. The inhibition by these fatty acids and acyl-CoAs was competitive with respect to the substrate, showing the K i values of 0.49-1.2µM. Site-directed mutagenesis of the substrate-binding residues of CBR1 suggested that the interactions between the fatty acyl chain and the enzyme's Met141 and Trp229 are important for the inhibitory selectivity. We also examined CBR1 inhibition by oleic acid in cellular levels: The fatty acid effectively inhibited CBR1-mediated 4-oxo-2-nonenal metabolism in colon cancer DLD1 cells and increased sensitivity to doxorubicin in the drug-resistant gastric cancer MKN45 cells that highly express CBR1. The results suggest a possible new food-drug interaction through inhibition of CBR1-mediated intestinal first-pass drug metabolism by dietary fatty acids. Copyright © 2017 Elsevier Inc. All rights reserved.

Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein

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Dorota Rowczenio

2017-05-01

Discussion: We report 6 novel mutations in the FGA gene: 5 were associated with renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to light-chain amyloid deposits discovered in a patient with a plasma cell dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis corroborated by genetic analysis and adequate typing using combined immunohistochemistry and laser microdissection and mass spectrometry is valuable to avoid misdiagnosis, especially when a family history of amyloidosis is absent.

2 : 2 Fe(III): ligand and "adamantane core" 4 : 2 Fe(III): ligand (hydr)oxo complexes of an acyclic ditopic ligand

DEFF Research Database (Denmark)

Ghiladi, Morten; Larsen, Frank B.; McKenzie, Christine J.

2005-01-01

A bis-hydroxo-bridged diiron(III) complex and a bis-mu-oxo-bis-mu-hydroxo-bridged tetrairon( III) complex are isolated from the reaction of 2,6-bis((N, N'-bis-(2-picolyl) amino) methyl)-4-tert-butylphenol (Hbpbp) with iron perchlorate in acidic and neutral solutions respectively. The X-ray struct......A bis-hydroxo-bridged diiron(III) complex and a bis-mu-oxo-bis-mu-hydroxo-bridged tetrairon( III) complex are isolated from the reaction of 2,6-bis((N, N'-bis-(2-picolyl) amino) methyl)-4-tert-butylphenol (Hbpbp) with iron perchlorate in acidic and neutral solutions respectively. The X...

De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

Science.gov (United States)

Tucci, Sara; Behringer, Sidney; Spiekerkoetter, Ute

2015-11-01

An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing. © 2015 FEBS.

A thermogravimetric analysis (TGA) method developed for estimating the stoichiometric ratio of solid-state {alpha}-cyclodextrin-based inclusion complexes

Energy Technology Data Exchange (ETDEWEB)

Bai, Yuxiang; Wang, Jinpeng; Bashari, Mohanad; Hu, Xiuting [The State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122 (China); Feng, Tao [School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418 (China); Xu, Xueming [The State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122 (China); Jin, Zhengyu, E-mail: jinlab2008@yahoo.com [The State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122 (China); Tian, Yaoqi, E-mail: yqtian@jiangnan.edu.cn [The State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122 (China)

2012-08-10

Highlights: Black-Right-Pointing-Pointer We develop a TGA method for the measurement of the stoichiometric ratio. Black-Right-Pointing-Pointer A series of formulas are deduced to calculate the stoichiometric ratio. Black-Right-Pointing-Pointer Four {alpha}-CD-based inclusion complexes were successfully prepared. Black-Right-Pointing-Pointer The developed method is applicable. - Abstract: An approach mainly based on thermogravimetric analysis (TGA) was developed to evaluate the stoichiometric ratio (SR, guest to host) of the guest-{alpha}-cyclodextrin (Guest-{alpha}-CD) inclusion complexes (4-cresol-{alpha}-CD, benzyl alcohol-{alpha}-CD, ferrocene-{alpha}-CD and decanoic acid-{alpha}-CD). The present data obtained from Fourier transform-infrared (FT-IR) spectroscopy showed that all the {alpha}-CD-based inclusion complexes were successfully prepared in a solid-state form. The stoichiometric ratios of {alpha}-CD to the relative guests (4-cresol, benzyl alcohol, ferrocene and decanoic acid) determined by the developed method were 1:1, 1:2, 2:1 and 1:2, respectively. These SR data were well demonstrated by the previously reported X-ray diffraction (XRD) method and the NMR confirmatory experiments, except the SR of decanoic acid with a larger size and longer chain was not consistent. It is, therefore, suggested that the TGA-based method is applicable to follow the stoichiometric ratio of the polycrystalline {alpha}-CD-based inclusion complexes with smaller and shorter chain guests.

Appearance and cellular distribution of lectin-like receptors for alpha 1-acid glycoprotein in the developing rat testis

DEFF Research Database (Denmark)

Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

1996-01-01

A histochemical avidin-biotin technique with three different alpha 1-acid glycoprotein glycoforms showed pronounced alterations in the cellular localization of two alpha 1-acid glycoprotein lectin-like receptors during cell differentiation in the developing rat testis. The binding of alpha 1-acid...

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

Directory of Open Access Journals (Sweden)

Marcilene Rezende Silva

2013-01-01

Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

A polymorphic variant in the human electron transfer flavoprotein alpha-chain (alpha-T171) displays decreased thermal stability and is overrepresented in very-long-chain acyl-CoA dehydrogenase-deficient patients with mild childhood presentation

DEFF Research Database (Denmark)

Bross, P; Pedersen, P; Nyholm, M

1999-01-01

The consequences of two amino acid polymorphisms of human electron transfer flavoprotein (alpha-T/I171 in the alpha-subunit and beta-M/T154 in the beta-subunit) on the thermal stability of the enzyme are described. The alpha-T171 variant displayed a significantly decreased thermal stability, wher....... This is compatible with a negative modulating effect of the less-stable alpha-T171 ETF variant in this group of VLCAD patients that harbor missense mutations in at least one allele and therefore potentially display residual levels of VLCAD enzyme activity. Udgivelsesdato: 1999-Jun...

Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men.

Science.gov (United States)

Rosell, Magdalena S; Lloyd-Wright, Zouë; Appleby, Paul N; Sanders, Thomas A B; Allen, Naomi E; Key, Timothy J

2005-08-01

Plasma concentrations of long-chain n-3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha-linolenic acid (18:3n-3; ALA). The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from 20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. The proportions of plasma long-chain n-3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.

Insufficient intake of alpha-linolenic fatty acid (18:3n-3 during pregnancy and associated factors

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Letícia Garcia VASCONCELOS

Full Text Available ABSTRACT Objective: To analyze alpha-linolenic fatty acid intake in two cohorts of pregnant women, and to identify factors associated with alpha-linolenic acid intake. Methods: This is a cohort study involving pregnant women with low obstetric risk (N=353 in public health system from a municipality of São Paulo state, Brazil. In each trimester, two 24-hour food recalls were collected. Descriptive analyses of dietary lipid profiles were performed, followed by a multiple comparison test. According to the trimester of pregnancy, differences were assessed using the mean difference test. To evaluate the adequacy of linoleic fatty acid and alpha-linolenic acid intake, the adequate intake test was used. The association between alpha-linolenic acid intake adequacy and maternal characteristics was investigated using a binary logistic regression model. Results: Total lipids intake and the percentage contribution to dietary energy met recommended levels. One-third of the diets demonstrated a lower than daily recommended intake of alpha-linolenic acid. Overweight pregnant women were twice as likely to have inadequate alpha-linolenic acid intake. Pregnant women from a more disadvantaged socioeconomic situation had greater risks of inadequate intake. Conclusion: Over-intake of lipids is not problematic, but quality is an issue, with one third of the pregnant women and their fetuses exposed to adverse effects due to low intake of omega-3 fatty acids, indicating important nutritional vulnerability in this population.

Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha

International Nuclear Information System (INIS)

Whiteheart, S.W.; Shenbagamurthi, P.; Chen, L.; Cotter, R.J.; Hart, G.W.

1989-01-01

Elongation Factor 1 alpha (EF-1 alpha), an important eukaryotic translation factor, transports charged aminoacyl-tRNA from the cytosol to the ribosomes during poly-peptide synthesis. Metabolic radiolabeling with [ 3 H] ethanolamine shows that, in all cells examined, EF-1 alpha is the major radiolabeled protein. Radiolabeled EF-1 alpha has an apparent Mr = 53,000 and a basic isoelectric point. It is cytosolic and does not contain N-linked oligosaccharides. Trypsin digestion of murine EF-1 alpha generated two major [ 3 H]ethanolamine-labeled peptides. Three peptides were sequenced and were identical to two distinct regions of the human EF-1 alpha protein. Blank sequencing cycles coinciding with glutamic acid in the human cDNA-derived sequence were also found to release [ 3 H]ethanolamine, and compositional analysis of these peptides confirmed the presence of glutamic acid. Dansylation analysis demonstrates that the amine group of the ethanolamine is blocked. These results indicate that EF-1 alpha is posttranslationally modified by the covalent attachment of ethanolamine via an amide bond to at least two specific glutamic acid residues (Glu-301 and Glu-374). The hydroxyl group of the attached ethanolamine was shown by mass spectrometry and compositional analysis, to be further modified by the addition of a phosphoglycerol unit. This novel posttranslational modification may represent an important alteration of EF-1 alpha, comparable to the regulatory effects of posttranslational methylation of EF-1 alpha lysine residues

Zeolites relieves inhibitory stress from high concentrations of long chain fatty acids.

Science.gov (United States)

Nordell, Erik; Hansson, Anna B; Karlsson, Martin

2013-12-01

Protein and fat rich slaughterhouse waste is a very attractive waste stream for the production of biogas because of the high biochemical methane potential of the substrate. The material has however some drawbacks as the sole material for biogas production due to the production of several process disturbing metabolites such as ammonia, sulfides and long chain fatty acids. We can in this work present results that show that zeolites have the potential to relieve inhibitory stress from the presence of long chain fatty acids. Moreover, the results strongly indicate that it is mainly acetic acid consumers that are most negatively affected by long chain fatty acids and that the mechanism of stress relief is an adsorption of long chain fatty acids to the zeolites. In addition to this, it is shown that the effect is immediate and that only a small amount of zeolites is necessary to cancel the inhibitory effect of long chain fatty acids. Copyright © 2013 Elsevier Ltd. All rights reserved.

Beta-alanine/alpha-ketoglutarate aminotransferase for 3-hydroxypropionic acid production

Science.gov (United States)

Jessen, Holly Jean [Chanhassen, MN; Liao, Hans H [Eden Prairie, MN; Gort, Steven John [Apple Valley, MN; Selifonova, Olga V [Plymouth, MN

2011-10-04

The present disclosure provides novel beta-alanine/alpha ketoglutarate aminotransferase nucleic acid and protein sequences having increased biological activity. Also provided are cells containing such enzymes, as well as methods of their use, for example to produce malonyl semialdehyde and downstream products thereof, such as 3-hydroxypropionic acid and derivatives thereof.

Rhenium(V) oxo complexes relevant to technetium renal imaging agents derived from mercaptoacetylglycylglycylaminobenzoic acid isomers. Structural and molecular mechanics studies

International Nuclear Information System (INIS)

Hansen, L.; Taylor, A. Jr; Marzilli, L.G.; Cini, R.

1992-01-01

The synthesis and characterization of three rhenium(V) oxo complexes derived from isomers of mercaptoacetylglycylglycylaminobenzoic acid (MAG 2 -ABAH 5 ) are reported. The isomers were synthesized from o-, m- and p-aminobenzoic acid and differed in the position of the terminal carboxyl group. The anions of 8-10, [ReO(MAG 2 -*ABAH)] - (* = para (8), meta (9), ortho (10)), contained the tetraanionic form of the ligands with the carboxyl group protonated. Compounds 8,9, and 10 were synthesized by exchange reactions of ReOCl 3 (Me 2 SO)(Ph 3 P) under moderate conditions and were isolated as [Ph 4 P] + , [Bu 4 N] + , and [Ph 4 P] + salts, respectively. The structures of 8 and 10 were determined by X-ray diffraction methods; except for the location of the carboxyl group, the structures are similar. The coordination geometry is pseudo square pyramidal, with nitrogen and sulfur donor atoms forming a square base and the oxo ligand at the apex. The orientation of the carboxyl group in 10 is anti to the Re double-bond O group. Since the carboxyl groups are protonated in 8 and 10 and in other relevant structures from this class of radiopharmaceuticals including [Ph 4 As][TcO(MAG 3 H)] (MAG 3 H = tetraanionic form of mercaptoacetyltriglycine), the authors developed molecular mechanics parameters that allowed them to calculate the structures of 8, 10, and [TcO(MAG 3 H)] - . They then extended the calculations to all three isomeric complexes in their deprotonated forms and to [TcO(MAG 3 )] 2- in order to approximate their solution phase structures. They conclude that the [TcO(MAG 3 )] 2- species is conformationally flexible, and they have made an initial assessment of structures vs renal clearance

Polymerase chain reaction system using magnetic beads for analyzing a sample that includes nucleic acid

Science.gov (United States)

Nasarabadi, Shanavaz [Livermore, CA

2011-01-11

A polymerase chain reaction system for analyzing a sample containing nucleic acid includes providing magnetic beads; providing a flow channel having a polymerase chain reaction chamber, a pre polymerase chain reaction magnet position adjacent the polymerase chain reaction chamber, and a post pre polymerase magnet position adjacent the polymerase chain reaction chamber. The nucleic acid is bound to the magnetic beads. The magnetic beads with the nucleic acid flow to the pre polymerase chain reaction magnet position in the flow channel. The magnetic beads and the nucleic acid are washed with ethanol. The nucleic acid in the polymerase chain reaction chamber is amplified. The magnetic beads and the nucleic acid are separated into a waste stream containing the magnetic beads and a post polymerase chain reaction mix containing the nucleic acid. The reaction mix containing the nucleic acid flows to an analysis unit in the channel for analysis.

Secretion of alpha 2-plasmin inhibitor is impaired by amino acid deletion in a small region of the molecule.

Science.gov (United States)

Toyota, S; Hirosawa, S; Aoki, N

1994-02-01

Alpha 2-plasmin inhibitor (alpha 2PI) deficiency Okinawa results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of the deletion of Glu137 in the amino acid sequence of alpha 2PI. To examine the effects of replacing the amino acid occupying position 137 or deleting its neighboring amino acid on alpha 2PI secretion, we used oligonucleotide-directed mutagenesis of alpha 2PI cDNA to change the codon specifying Glu137 or delete a codon specifying its neighboring amino acid. The effects were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of media from transiently transfected COS-7 cells. Replacement of Glu137 with an amino acid other than Cys had little effect on alpha 2PI secretion. In contrast, deletion of an amino acid in a region spanning a sequence of less than 30 amino acids including positions 127 and 137 severely impaired the secretion. The results suggest that structural integrity of the region, rather than its component amino acids, is important for the intracellular transport and secretion of alpha 2PI.

Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as peroxisome proliferator-activated receptor alpha agonists.

Science.gov (United States)

Giampietro, Letizia; Ammazzalorso, Alessandra; Giancristofaro, Antonella; Lannutti, Fabio; Bettoni, Giancarlo; De Filippis, Barbara; Fantacuzzi, Marialuigia; Maccallini, Cristina; Petruzzelli, Michele; Morgano, Annalisa; Moschetta, Antonio; Amoroso, Rosa

2009-10-22

A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human peroxisome proliferator-activated receptor alpha (PPARalpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor alpha were screened for activity against the PPARgamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.

The Use of 4-(3,4-Dichlorophenyl-4-Oxo-2-(4-Antipyrinyl-Butanoic Acid in the Preparation of Some New Heterocyclic Compounds With Expected Biological Activity

Directory of Open Access Journals (Sweden)

M. Shafik

2003-03-01

Full Text Available Reaction of 4-oxo-4-(3,4-dichlorophenyl-2-butenoic acid (1 with antipyrin (2 gave the corresponding butanoic acid 3. Reaction of 3 with hydrazines gave the pyridazinone derivatives 5a,b. Compounds 5a,b were used to prepare the corresponding dithio derivatives. Reaction of 5a with POCl3 unexpectedly gave the chloropyridazine derivative 7, which is used to prepare the corresponding thio derivative. The hitherto unknown reactions of this chloro derivative with 2-amino-3-carbethoxy-4,5-dimethylthiophene and 2-amino-3-carbethoxy tetrahydrobenzothiophene have now been described. The behaviour of the chloro derivative toward hydrazine hydrate, sodium azide and anthranilic acid was also studied. Some of the new compounds showed antimicrobial and antifungal activities .

5-Methyl-4-oxo-4,6-dihydro-3H-pyridazino[4,5-b]carbazole-1-carbonitrile

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Norbert Haider

2010-02-01

Full Text Available The title compound was prepared in excellent yield from 5-methyl-4-oxo-4,6-dihydro-3H-pyridazino[4,5-b]carbazole-1-carbaldehyde by treatment with hydroxylamine hydrochloride in formic acid without isolation of the intermediate oxime.

Effect of alpha 2-adrenoceptor agonists on gastric pepsin and acid secretion in the rat.

Science.gov (United States)

Tazi-Saad, K.; Chariot, J.; Del Tacca, M.; Rozé, C.

1992-01-01

1. The purpose of the present study was to analyze the effects of the alpha 2-adrenoceptor agonists clonidine, guanabenz, detomidine and medetomidine on pepsin secretion in conscious rats provided with gastric chronic fistula and to compare this with acid secretion. 2. Basal interdigestive gastric secretion, which is mainly neurally driven in the rat, and the secretion directly stimulated by the two main stimulants of chief cells, cholecystokinin octapeptide (CCK8) and methacholine, were studied. 3. Basal secretion of pepsin and acid was inhibited by all four drugs with comparable EC50S. 4. CCK-stimulated pepsin and acid secretion was less sensitive than basal pepsin and acid secretion to alpha 2-adrenoceptor inhibition. 5. Methacholine-stimulated pepsin and acid secretion was not changed by clonidine and guanabenz; methacholine-stimulated acid was even marginally increased by clonidine. 6. These results do not favour the presence of alpha 2-receptors on chief cells in the rat stomach. They rather suggest that pepsin inhibition by alpha 2-adrenoceptor agonists is indirect and due to central or peripheral inhibition of the discharge of nerve fibres activating pepsin secretion. PMID:1356566

An NMR and ab initio quantum chemical study of acid-base equilibria for conformationally constrained acidic alpha-amino acids in aqueous solution

DEFF Research Database (Denmark)

Nielsen, Peter Aadal; Jaroszewski, Jerzy W.; Norrby, Per-Ola

2001-01-01

The protonation states of a series of piperidinedicarboxylic acids (PDAs), which are conformationally constrained acidic alpha -amino acids, have been studied by C-13 NMR titration in water. The resulting data have been correlated with theoretical results obtained by HF/6-31+G* calculations using...

Oxo-group-14-element bond formation in binuclear uranium(V) pacman complexes

International Nuclear Information System (INIS)

Jones, Guy M.; Arnold, Polly L.; Love, Jason B.

2013-01-01

Simple and versatile routes to the functionalization of uranyl-derived U"V-oxo groups are presented. The oxo-lithiated, binuclear uranium(V)-oxo complexes [{(py)_3LiOUO}_2(L)] and [{(py)_3LiOUO}(OUOSiMe_3)(L)] were prepared by the direct combination of the uranyl(VI) silylamide ''ate'' complex [Li(py)_2][(OUO)(N'')_3](N''=N(SiMe_3)_2) with the polypyrrolic macrocycle H_4L or the mononuclear uranyl (VI) Pacman complex [UO_2(py)(H_2L)], respectively. These oxo-metalated complexes display distinct U-O single and multiple bonding patterns and an axial/equatorial arrangement of oxo ligands. Their ready availability allows the direct functionalization of the uranyl oxo group leading to the binuclear uranium(V) oxo-stannylated complexes [{(R_3Sn)OUO}_2(L)] (R=nBu, Ph), which represent rare examples of mixed uranium/tin complexes. Also, uranium-oxo-group exchange occurred in reactions with [TiCl(OiPr)_3] to form U-O-C bonds [{(py)_3LiOUO}(OUOiPr)(L)] and [(iPrOUO)_2(L)]. Overall, these represent the first family of uranium(V) complexes that are oxo-functionalised by Group 14 elements. (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA): results from the alpha omega trial

NARCIS (Netherlands)

Brouwer, Ingeborg A.; Geleijnse, Johanna M.; Klaasen, Veronique M.; Smit, Liesbeth A.; Giltay, Erik J.; de Goede, Janette; Heijboer, Annemieke C.; Kromhout, Daan; Katan, Martijn B.

2013-01-01

Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of

Growth-Environment Dependent Modulation of Staphylococcus aureus Branched-Chain to Straight-Chain Fatty Acid Ratio and Incorporation of Unsaturated Fatty Acids.

Science.gov (United States)

Sen, Suranjana; Sirobhushanam, Sirisha; Johnson, Seth R; Song, Yang; Tefft, Ryan; Gatto, Craig; Wilkinson, Brian J

2016-01-01

The fatty acid composition of membrane glycerolipids is a major determinant of Staphylococcus aureus membrane biophysical properties that impacts key factors in cell physiology including susceptibility to membrane active antimicrobials, pathogenesis, and response to environmental stress. The fatty acids of S. aureus are considered to be a mixture of branched-chain fatty acids (BCFAs), which increase membrane fluidity, and straight-chain fatty acids (SCFAs) that decrease it. The balance of BCFAs and SCFAs in USA300 strain JE2 and strain SH1000 was affected considerably by differences in the conventional laboratory medium in which the strains were grown with media such as Mueller-Hinton broth and Luria broth resulting in high BCFAs and low SCFAs, whereas growth in Tryptic Soy Broth and Brain-Heart Infusion broth led to reduction in BCFAs and an increase in SCFAs. Straight-chain unsaturated fatty acids (SCUFAs) were not detected. However, when S. aureus was grown ex vivo in serum, the fatty acid composition was radically different with SCUFAs, which increase membrane fluidity, making up a substantial proportion of the total (37%) and BCFAs (>36%) making up the rest. Staphyloxanthin, an additional major membrane lipid component unique to S. aureus, tended to be greater in content in cells with high BCFAs or SCUFAs. Cells with high staphyloxanthin content had a lower membrane fluidity that was attributed to increased production of staphyloxanthin. S. aureus saves energy and carbon by utilizing host fatty acids for part of its total fatty acids when growing in serum, which may impact biophysical properties and pathogenesis given the role of SCUFAs in virulence. The nutritional environment in which S. aureus is grown in vitro or in vivo in an infection is likely to be a major determinant of membrane fatty acid composition.

The associations between serum adiponectin, leptin, C-reactive protein, insulin, and serum long-chain omega-3 fatty acids in Labrador Retrievers

Directory of Open Access Journals (Sweden)

Streeter RM

2015-04-01

Full Text Available Renee M Streeter,1 Angela M Struble,1 Sabine Mann,2 Daryl V Nydam,2 John E Bauer,3 Marta G Castelhano,1 Rory J Todhunter,1 Bethany P Cummings,4 Joseph J Wakshlag11Department of Clinical Sciences, 2Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA; 3Department of Clinical Sciences, Texas A&M University, College Station, TX, USA; 4Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USAAbstract: Obesity has been associated with an increased inflammatory response and insulin resistance due to adipose tissue–derived adipokines and increases in C-reactive protein (CRP. Dogs appear to be similar to other species with the exception of adiponectin, which might not be affected by obesity status. Serum long-chain polyunsaturated fatty acid concentrations have been positively and negatively associated with serum adipokines. The aim of the study was to examine the relationship between leptin, CRP, adiponectin, and insulin to body condition score (BCS and to the long-chain omega-3 fatty acids in serum lipoproteins, including alpha-linolenic acid, eicosapentaenoic acid (EPA, docosapentanenoic acid (DPA, and docosahexaenoic acid (DHA as a reflection of dietary omega-3 status in the Labrador Retriever. Seventy-seven Labrador Retrievers were evaluated for BCS, percent fasting serum lipoprotein fatty acid concentrations, as well as serum leptin, adiponectin, insulin, and CRP. A multivariable general linear regression model was constructed to examine the association between the dependent variables leptin, CRP, adiponectin, and insulin and the predictor variables of BCS, age, and sex, as well as concentrations of alpha-linolenic acid, EPA, DHA, and DPA. Adiponectin concentration was positively associated with age (P<0.0008, EPA (P=0.027 and negatively associated with DHA (P=0.008. Leptin concentration was positively associated with an increased DHA (P=0.009, BCS (P

The remarkable stability of chimeric, sialic acid-derived alpha/delta-peptides in human blood plasma.

Science.gov (United States)

Saludes, Jonel P; Natarajan, Arutselvan; DeNardo, Sally J; Gervay-Hague, Jacquelyn

2010-05-01

Peptides are labile toward proteolytic enzymes, and structural modifications are often required to prolong their metabolic half-life and increase resistance. One modification is the incorporation of non-alpha-amino acids into the peptide to deter recognition by hydrolytic enzymes. We previously reported the synthesis of chimeric alpha/delta-peptides from glutamic acids (Glu) and the sialic acid derivative Neu2en. Conformational analyses revealed these constructs adopt secondary structures in water and may serve as conformational surrogates of polysialic acid. Polysialic acid is a tumor-associated polysaccharide and is correlated with cancer metastasis. Soluble polysialic acid is rapidly cleared from the blood limiting its potential for vaccine development. One motivation in developing structural surrogates of polysialic acid was to create constructs with increased bioavailability. Here, we report plasma stability profiles of Glu/Neu2en alpha/delta-peptides. DOTA was conjugated at the peptide N-termini by solid phase peptide synthesis, radiolabeled with (111)In, incubated in human blood plasma at 37 degrees C, and their degradation patterns monitored by cellulose acetate electrophoresis and radioactivity counting. Results indicate that these peptides exhibit a long half-life that is two- to three-orders of magnitude higher than natural alpha-peptides. These findings provide a viable platform for the synthesis of plasma stable, sialic acid-derived peptides that may find pharmaceutical application.

Straight and branched-chain fatty acids in preorbital glands of sika deer, Cervus nippon.

Science.gov (United States)

Wood, William F

2004-02-01

Using GC-MS analysis, 11 major volatile compounds were found in the preorbital gland secretion from a female sika deer, Cervus nippon. These compounds are the C14 through C18 straight-chain fatty acids, (ZZ)-9,12-octadecadienoic acid, 12-methyltridecanoic acid, 13-methyltetradecanoic acid, 14-methylpentadecanoic acid, 14-methylhexadecanoic acid, and 15-methylhexadecanoic acid. The five branched-chain acids make up over 29% of the volatiles in the gland. This is the first time branched-chain carboxylic acids have been reported from ungulate preorbital glands.

[Odd- and branched-chain fatty acids in milk fat--characteristic and health properties].

Science.gov (United States)

Adamska, Agata; Rutkowska, Jarosława

2014-08-22

This review analyzes the current state of knowledge on odd- and branched-chain fatty acids present in milk fat. Special attention is devoted to the characteristic, synthesis in ruminants, factors affecting their content in milk fat and pro-health properties of these compounds. The group of odd- and branched-chain fatty acids includes mainly saturated fatty acids with one or more methyl branches in the iso or anteiso position. These fatty acids are largely derived from ruminal bacteria and they have been transferred to ruminant tissue (milk and meat). For that reason they have been used as biomarkers of rumen fermentation. Odd- and branched-chain fatty acids are exogenous products for humans, and therefore have specific properties. The results of research from recent decades show that odd- and branched-chain fatty acids have anti-cancer activity. Branched-chain fatty acids may reduce the incidence of necrotizing enterocolitis. Additionally, these compounds have a beneficial effect on proper tissue function and on functioning and development of the infant gut, whereas odd-chain fatty acids are considered as biomarkers of milk fat intake by humans. So far, not all the mechanisms of activity of these compounds are known thoroughly. They should be more carefully studied for application of their biological effects in prevention and treatment.

Aloe vera extract reduces 8-oxo-2'-deoxyguanosine levels and improves total antioxidants in streptozotocin-induced diabetic rats

Directory of Open Access Journals (Sweden)

Wulan Christijanti

2017-04-01

Full Text Available Background Diabetes mellitus is a chronic disease caused by lack of insulin production in the pancreas or by insulin resistance, the disease being characterized by elevated blood glucose levels. Hyperglycemia in diabetes could lead to oxidative stress due to the rise in 8-oxo-2'-deoxyguanosine (8-oxo-dG levels and the decrease in levels of total antioxidant status (TAS. The purpose of this study was to assess the effect Aloe vera extract on 8-oxo-dG level and total antioxidant status in diabetic rat testis.   Methods This was an experimental laboratory study with 20 rat samples which were divided into 4 groups (1 control group and 3 treatment groups. Diabetes was induced in the rats by streptozotocin (STZ at 65 mg/kgBW. The diabetic rats were then treated for 28 days with Aloe vera extract at 0 mg (P0, 200 mg rind (P1, 200 mg pulp (P2, respectively. The level of 8 -oxo-dG was measured by ELISA and total antioxidant status with 2,2' -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS. Data were analyzed with ANOVA and Least Significant Difference Advanced Test at P<0.05.   Results 8-Oxo-dG levels were significantly different between the control group and both P0 and P2, but not between the control group and P1. Among the treatment groups the 8-oxo-dG levels were significantly different. Mean total antioxidant status was significantly different between control and treatment groups, and also between treatment groups (p<0.05.   Conclusions Aloe vera extract reduced free radicals (level of 8-oxo-dG and increased the total antioxidant status in diabetic rat testis.

Oxo-group-14-element bond formation in binuclear uranium(V) pacman complexes

Energy Technology Data Exchange (ETDEWEB)

Jones, Guy M.; Arnold, Polly L.; Love, Jason B. [EaStCHEM School of Chemistry, University of Edinburgh (United Kingdom)

2013-07-29

Simple and versatile routes to the functionalization of uranyl-derived U{sup V}-oxo groups are presented. The oxo-lithiated, binuclear uranium(V)-oxo complexes [{(py)_3LiOUO}{sub 2}(L)] and [{(py)_3LiOUO}(OUOSiMe{sub 3})(L)] were prepared by the direct combination of the uranyl(VI) silylamide ''ate'' complex [Li(py){sub 2}][(OUO)(N''){sub 3}](N''=N(SiMe{sub 3}){sub 2}) with the polypyrrolic macrocycle H{sub 4}L or the mononuclear uranyl (VI) Pacman complex [UO{sub 2}(py)(H{sub 2}L)], respectively. These oxo-metalated complexes display distinct U-O single and multiple bonding patterns and an axial/equatorial arrangement of oxo ligands. Their ready availability allows the direct functionalization of the uranyl oxo group leading to the binuclear uranium(V) oxo-stannylated complexes [{(R_3Sn)OUO}{sub 2}(L)] (R=nBu, Ph), which represent rare examples of mixed uranium/tin complexes. Also, uranium-oxo-group exchange occurred in reactions with [TiCl(OiPr){sub 3}] to form U-O-C bonds [{(py)_3LiOUO}(OUOiPr)(L)] and [(iPrOUO){sub 2}(L)]. Overall, these represent the first family of uranium(V) complexes that are oxo-functionalised by Group 14 elements. (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Ligand assisted cleavage of uranium oxo-clusters

Energy Technology Data Exchange (ETDEWEB)

Nocton, Gregory; Pecaut, Jacques; Mazzanti, Marinella [Laboratoire de Reconnaissance Ionique et Chimie de Coordination, Service de Chimie Inorganique et Biologique, UMR-E 3 CEA-UJF, CEA/DSM/INAC, CEA-Grenoble, 38054 Grenoble, Cedex 09 (France); Filinchuk, Yaroslav [Swiss Norwegian Beam Lines (SNBL) at the European Synchrotron Radiation Facility (ESRF), rue Jules Horowitz, 38043 Grenoble (France)

2010-07-01

Dibenzoylmethanate replaces the bridging triflate ligands in uranium triflate poly-oxo-clusters and cleaves the U{sub 12}O{sub 20} core yielding the new [U{sub 6}O{sub 4}(OH){sub 4}({eta}-dbm){sub 12}] dibenzoylmethanate (dbm{sup -}) cluster which slowly dissociates into a monomeric complex. This reactivity demonstrates the importance of bridging ligands in stabilizing uranium poly-oxo-clusters. (authors)

Inter-laboratory validation of procedures for measuring 8-oxo-7,8-dihydrooxoguanine/8-oxo-7,8-dihydro-2`-deoxyguanosine in DNA

DEFF Research Database (Denmark)

Collins, A.R.; Gedik, C.M.; Wood, S.

2002-01-01

The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG...

Influence of biopolymers on the solubility of branched-chain amino acids and stability of their solutions.

Science.gov (United States)

Hong, Chi Rac; Lee, Gyu Whan; Paik, Hyun-Dong; Chang, Pahn-Shick; Choi, Seung Jun

2018-01-15

This study confirmed the possibility of biopolymer-type stabilizers to increase the saturation concentration of branched-chain amino acids by preventing their crystallization/precipitation. Although microfluidization increased the initial solubility, it failed to increase the saturation concentration of the branched-chain amino acids. The saturation concentration of the branched-chain amino acids increased from 3.81% to 4.42% and 4.85% after the incorporation of food hydrocolloids and proteins, respectively. However, the branched-chain amino acids:stabilizer ratio did not affect the solubility. In the case of food hydrocolloid-based solutions, crystal formation and growth of branched-chain amino acids occurred during storage, resulting in the precipitation of branched-chain amino acid crystals. However, food proteins effectively increased the stability of the solubilized branched-chain amino acids. The improved solubility and stability of the solubilized branched-chain amino acids could be attributed to interactions between the functional groups (carboxyl, amine, sulfate, aliphatic, aromatic, etc.) of the stabilizer and the branched-chain amino acid molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Dietary supplementation of obese children with 1000 mg alpha-linolenic acid per day: a placebo-controlled double blind study].

Science.gov (United States)

Lohner, Szimonetta; Marosvölgyi, Tamás; Burus, István; Schmidt, János; Molnár, Dénes; Decsi, Tamás

2007-08-12

Enhanced dietary intake of omega-3 fatty acids may benefit persons with increased cardiovascular risk, among them obese subjects. Incorporation of omega-3 fatty acids into the plasma lipids is a prerequisite to achieve the favorable effects; however, only very few data are available on the dose of omega-3 fatty acid supplementation in children. The aim of our study was to examine the effects of the consumption of a diet supplemented with 1000 mg alpha-linolenic acid daily on plasma lipids in obese children. In this two times six-week-long, placebo-controlled, crossover study, 9 obese children (age: 13.1 [2.5] years, body mass index: 31.2 [6.2] kg/m 2 ), median [IQR]) incorporated into their diet one egg and one meatball (50 g) per day from hens fed diets containing flaxseed oil, i.e. supplementary dietary intake of 1000 mg alpha-linolenic acid per day was provided. The fatty acid composition of plasma lipids was determined by high-resolution gas-liquid chromatography. Tendencies of increase were observed in the alpha-linolenic acid content of plasma lipids in the phospholipid, triacyl-glycerine and sterol-ester fractions after the supplementation with alpha-linolenic acid. In the non-esterified fatty acid fraction, the values of alpha-linolenic acid were significantly higher after the supplementation (0.11 [0.08] versus 0.14 [0.20], % weight/weight, p < 0.05), indicating the beginning of the accumulation of alpha-linolenic acid in plasma lipids. In obese children a six-week-long supplementation of the diet with 1000 mg alpha-linolenic acid per day increased significantly the contribution of omega-3 fatty acids only to the non-esterified fatty acids of plasma lipids, but had no significant effect on the esterified fractions. Increase of the dose of supplementation may be needed to influence omega-3 fatty acid status in obese children.

Association between very long chain fatty acids in the meibomian gland and dry eye resulting from n-3 fatty acid deficiency.

Science.gov (United States)

Tanaka, Hideko; Harauma, Akiko; Takimoto, Mao; Moriguchi, Toru

2015-06-01

In our previously study, we reported lower tear volume in with an n-3 fatty acid deficient mice and that the docosahexaenoic acid and total n-3 fatty acid levels in these mice are significantly reduced in the meibomian gland, which secretes an oily tear product. Furthermore, we noted very long chain fatty acids (≥25 carbons) in the meibomian gland. To verify the detailed mechanism of the low tear volume in the n-3 fatty acid-deficient mice, we identified the very long chain fatty acids in the meibomian gland, measured the fatty acid composition in the tear product. Very long chain fatty acids were found to exist as monoesters. In particular, very long chain fatty acids with 25-29 carbons existed for the most part as iso or anteiso branched-chain fatty acids. n-3 fatty acid deficiency was decreased the amount of meibum secretion from meibomian gland without change of fatty acid composition. These results suggest that the n-3 fatty acid deficiency causes the enhancement of evaporation of tear film by reducing oily tear secretion along with the decrease of meibomian gland function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Addition of alpha-ketoglutarate enhances formation of volatiles by Staphylococcus carnosus during sausage fermentation

DEFF Research Database (Denmark)

Tjener, Karsten; Stahnke, Louise Heller; Andersen, L.

2004-01-01

The effect of leucine and alpha-ketoglutarate addition on transamination of branched-chain amino acids was studied in model minces inoculated with Pediococcus pentosaceus and Staphylococcus carnosus. Leucine addition changed the ratio of volatile breakdown products of leucine, isoleucine and valine....... The results were verified in real fermented sausages with no, low (0.09% w/w) and high (0.36% w/w) addition of added alpha-ketoglutarate since the levels of the flavour intensive methyl-branched aldehydes and acids were drastically increased in sausages added a-ketoglutarate. The catabolism of phenylalanine...

Uptake of neutral alpha- and beta-amino acids by human proximal tubular cells

DEFF Research Database (Denmark)

Jessen, H; Røigaard, H; Jacobsen, Christian

1996-01-01

experiments revealed that all the neutral amino acids tested reduced the uptake of AIB, whereas there was no effect of taurine, L-aspartic acid, and L-arginine. By contrast, the influx of beta-alanine was only drastically reduced by beta-amino acids, whereas the inhibition by neutral alpha-amino acids...

Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

Science.gov (United States)

Cynober, L; Coudray-Lucas, C; de Bandt, J P; Guéchot, J; Aussel, C; Salvucci, M; Giboudeau, J

1990-02-01

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract.

Science.gov (United States)

Abe, Masayuki; Ito, Yoshihiko; Oyunzul, Luvsandorj; Oki-Fujino, Tomomi; Yamada, Shizuo

2009-04-01

Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine (1,4-DHP) calcium channel antagonist receptors. Major constituents of SPE are lauric acid, oleic acid, myristic acid, palmitic acid and linoleic acid. The aim of this study was to investigate binding affinities of these fatty acids for pharmacologically relevant (alpha(1)-adrenergic, muscarinic and 1,4-DHP) receptors. The fatty acids inhibited specific [(3)H]prazosin binding in rat brain in a concentration-dependent manner with IC(50) values of 23.8 to 136 microg/ml, and specific (+)-[(3)H]PN 200-110 binding with IC(50) values of 24.5 to 79.5 microg/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [(3)H]N-methylscopolamine ([(3)H]NMS) binding in rat brain with IC(50) values of 56.4 to 169 microg/ml. Palmitic acid had no effect on specific [(3)H]NMS binding. The affinity of oleic acid, myristic acid and linoleic acid for each receptor was greater than the affinity of SPE. Scatchard analysis revealed that oleic acid and lauric acid caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]prazosin, [(3)H]NMS and (+)-[(3)H]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to alpha(1)-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5alpha-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5alpha-reductase activity in rat liver with an IC(50) of 101 microg/ml. Similarly, all the fatty acids except palmitic acid inhibited 5alpha-reductase activity, with IC(50) values of 42.1 to 67.6 microg/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of alpha(1)-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5

The lipoxygenase pathway in tulip (Tulipa gesneriana): detection of the ketol route.

Science.gov (United States)

Grechkin, A N; Mukhtarova, L S; Hamberg, M

2000-12-01

The in vitro metabolism of [1-(14)C]linoleate, [1-(14)C]linolenate and their 9(S)-hydroperoxides was studied in cell-free preparations from tulip (Tulipa gesneriana) bulbs, leaves and flowers. Linoleate and its 9-hydroperoxide were converted by bulb and leaf preparations into three ketols: (12Z)-9-hydroxy-10-oxo-12-octadecadienoic acid (alpha-ketol), (11E)-10-oxo-13-hydroxy-11-octadecadienoic acid (gamma-ketol) and a novel compound, (12Z)-10-oxo-11-hydroxy-12-octadecadienoic acid (10,11-ketol), in the approximate molar proportions of 10:3:1. The corresponding 15, 16-dehydro alpha- and gamma-ketols were the main metabolites of [1-(14)C]linolenate and its 9-hydroperoxide. Thus bulbs and leaves possessed 9-lipoxygenase and allene oxide synthase activities. Incubations with flower preparations gave alpha-ketol hydro(pero)xides as predominant metabolites. Bulb and leaf preparations possessed a novel enzyme activity, gamma-ketol reductase, which reduces gamma-ketol to 10-oxo-13-hydroxyoctadecanoic acid (dihydro-gamma-ketol) in the presence of NADH. Exogenous linolenate 13(S)-hydroperoxide was converted mostly into chiral (9S,13S)-12-oxo-10-phytodienoate (99.5% optical purity) by bulb preparations, while [1-(14)C]linolenate was a precursor for ketols only. Thus tulip bulbs possess abundant allene oxide cyclase activity, the substrate for which is linolenate 13(S)-hydroperoxide, even though 13(S)-lipoxygenase products were not detectable in the bulbs. The majority of the cyclase activity was found in the microsomes (10(5) g pellet). Cyclase activity was not found in the other tissues examined, but only in the bulbs. The ketol route of the lipoxygenase pathway, mediated by 9-lipoxygenase and allene oxide synthase activities, has not been detected previously in the vegetative organs of any plant species.

Synthesis of (19E)-3 beta,7 alpha-dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime, a new hapten for 7 alpha-hydroxydehydroepiandrosterone (3 beta,7 alpha-dihydroxyandrost-5-en-17-one).

Science.gov (United States)

Pouzar, V; Slavíková, T; Cerńy, I

1998-09-01

The title compound was prepared in 11 steps from 17,17-ethylenedioxy-19-hydroxyandrost-5-en-3 beta-yl acetate. After tert-butyldimethylsilyl protection of the 19-hydroxyl group, a 7-oxo group was introduced by oxidation with 3,5-dimethylpyrazole-chromium trioxide complex, and then selectively reduced with L-Selectride to give a 7 alpha-hydroxy derivative. This partially protected triol was acetylated and desilylated to 3,7-diacetate. Subsequent oxidation with pyridine-chromium trioxide complex gave 19-aldehyde, which was transformed into the corresponding protected 19-(O-carboxymethyl)oxime. Successive ketal cleavage, deacetylation, and methyl ester splitting gave the final (19E)-3 beta,7 alpha-dihydroxy-17-oxoandrost-5-en-19-al 19-(O-carboxymethyl)oxime, designed as a hapten for 7 alpha-hydroxydehydroepiandrosterone immunoassays.

Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans

DEFF Research Database (Denmark)

Larsen, Emil List; Cejvanovic, Vanja; Kjaer, Laura Kofoed

2017-01-01

, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation.......7% (95% CI: 5.8–37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. Conclusion Clarithromycin significantly increases oxidative nucleic acid...... modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications....

gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status

NARCIS (Netherlands)

Brouwer, DAJ; Hettema, Y; van Doormaal, JJ; Muskiet, FAJ

Augmentation of long chain polyunsaturated omega 3 fatty acid (LCPUFA omega 3) status can be reached by consumption of fish oil or by improvement of the conversion of a-linolenic acid (ALA) to LCPUFA omega 3. Since gamma-linolenic acid (GLA) might activate the rate-limiting Delta-6 desaturation, we

Transamination of branched chain amino acids (BCAA) in rat adipose tissue

Energy Technology Data Exchange (ETDEWEB)

Frick, G.P.; Goodman, H.M.

1986-03-05

Like most extrahepatic tissues, adipose tissue can transaminate the BCAA faster than they are oxidized. Catabolism of the BCAA by adipose tissue appears to be limited by the activity of branched chain ..cap alpha..-keto acid dehydrogenase (BCDH). Conditions which stimulate the activity of this intramitochondrial enzyme in tissue extracts also increase the rate at which (1-/sup 14/C)leucine (L) and (1-/sup 14/C)valine (V) are oxidized by tissue segments. However, when maximum rates of oxidation were measured, 10 mM L was oxidized to /sup 14/CO/sub 2/ 5 times faster than 10 mM V (30 +/- 2 vs. 6 +/- 1 nmol min/sup -1/ g tis/sup -1/). In contrast, the ..cap alpha..-keto analogs of L and V were oxidized by tissue segments at nearly equal rates which slightly exceeded the rate of L oxidation. These results suggested that transamination might limit the catabolism of V, perhaps due to its inaccessibility to transaminase. The distribution of transaminase activity in tissue extracts was determined after centrifugation to obtain mitochondrial and cytosolic fractions. L and V were transaminated at similar rates by enzymes in both fractions. Transaminase activity in the mitochondrial fraction was greater than that of the cytosol and exceeded the capacity of the tissue to oxidize L. Catabolism of BCAA may depend upon intramitochondrial transamination and oxidation of V may be slower than that of L because uptake of V by mitochondria may be slower than that of L.

Odd- and branched-chain fatty acids in milk fat – characteristic and health properties

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Agata Adamska

2014-08-01

Full Text Available This review analyzes the current state of knowledge on odd- and branched-chain fatty acids present in milk fat. Special attention is devoted to the characteristic, synthesis in ruminants, factors affecting their content in milk fat and pro-health properties of these compounds. The group of odd- and branched-chain fatty acids includes mainly saturated fatty acids with one or more methyl branches in the iso or anteiso position. These fatty acids are largely derived from ruminal bacteria and they have been transferred to ruminant tissue (milk and meat. For that reason they have been used as biomarkers of rumen fermentation. Odd- and branched-chain fatty acids are exogenous products for humans, and therefore have specific properties. The results of research from recent decades show that odd- and branched-chain fatty acids have anti-cancer activity. Branched-chain fatty acids may reduce the incidence of necrotizing enterocolitis. Additionally, these compounds have a beneficial effect on proper tissue function and on functioning and development of the infant gut, whereas odd-chain fatty acids are considered as biomarkers of milk fat intake by humans. So far, not all the mechanisms of activity of these compounds are known thoroughly. They should be more carefully studied for application of their biological effects in prevention and treatment.

Stability of HAMLET--a kinetically trapped alpha-lactalbumin oleic acid complex.

Science.gov (United States)

Fast, Jonas; Mossberg, Ann-Kristin; Svanborg, Catharina; Linse, Sara

2005-02-01

The stability toward thermal and urea denaturation was measured for HAMLET (human alpha-lactalbumin made lethal to tumor cells) and alpha-lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than alpha-lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15 degrees C lower for apo HAMLET than for apo alpha-lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than alpha-lactalbumin, although it is a complex of alpha-lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol.

Comparative study of reactions between µ-nitrido- or µ-oxo-bridged iron tetrasulfophthalocyanines and sulfur-containing reductants

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Dereven’kov Ilia A.

2013-01-01

Full Text Available A comparative study of reactivity of μ-nitrido- and μ-oxo-dimers of iron tetrasulfophthalocyanine has been performed in aqueous solutions of various acidity. The substantially higher stability of nitrido-bridged structure under both strongly acidic and strongly alkaline environments was demonstrated. Reactions of the complexes with sulfur-containing reductants (sodium dithionite, thiourea dioxide, sodium hydroxymethanesulfinate, L-cysteine has been studied. Differences in reduction processes were explained.

Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus.

Science.gov (United States)

Okanović, Azra; Prnjavorac, Besim; Jusufović, Edin; Sejdinović, Rifat

2015-08-01

To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Lower critical solution temperature behavior of alpha-substituted poly(acrylic acids)s, cyclopolymerization of N-vinylformamido-methylacrylates, and use of the World-Wide Web in polymer science education

Science.gov (United States)

Michalovic, Mark Stephen

A series of alpha-substituted poly(acrylic acid)s was synthesized and characterized. Their aqueous solution properties were investigated with respect to lower critical solution temperature (LCST) behavior. Poly(alpha-methoxymethylacrylic acid) was found to have a lower critical solution temperature (LCST) of 46°C, poly(alpha-methoxyethoxymethylacrylic acid) showed an LCST of 26.5°C and poly(alpha-methoxyethoxyethoxymethylacrylic acid) showed an LCST of 66°C. The cloud points of the solutions of these polymers were found to be sensitive to pH, and to concentrations of additives such as urea, salts, and surfactants. Because of low molecular weight due to chain transfer, high molecular weight analogs of the ether-linked polymers were synthesized in which ester linkages joined the oligo-oxyethylene segment to the acrylate moiety. Poly(alpha-methoxyethoxyacetoxymethylacrylic acid) was the only one of this series to give an LCST with a value of 52.5°C. Copolymers of t-butyl alpha-methoxymethylacrylate (tBMMA) with alpha-(1H,1H- perfluorooctyloxymethyl)acrylic acid (PFOMA) were synthesized, deprotected and their lower critical solution temperatures (LCSTs) evaluated. At PFOMA feed ratios of 0.25 mol % or less, no observable change in the LCST was observed, while at PFOMA feed ratios of above 0.25 mol % to 1.125 mol %, a large linear decrease in the LCST was observed with increasing fluorocarbon content. t-Butyl alpha-(N-vinylformamidomethyl)acrylate (tBVFA) and ethyl alpha-(N-vinylformamidomethyl)acrylate (EVFA) were synthesized from t-butyl alpha-bromomethylacrylate and ethyl alpha-chloromethylacrylate, respectively. tBVFA was found to cyclopolymerize at 120°C in DMF, DMSO, and 1,2-dichlorobenzene at solvent:monomer ratios of 10:1 vol:wt. Molecular weights for poly(tBVFA) ranged from 10,000 to 13,000 as estimated by size-exclusion chromatography. At lower solvent monomer ratio (1:1), and at lower temperature (71°C), crosslinking occurred. EVFA was found to

Bile acid metabolism in cirrhosis. VIII. Quantitative evaluation of bile acid synthesis from [7 beta-3H]7 alpha-hydroxycholesterol and [G-3H]26-hydroxycholesterol

International Nuclear Information System (INIS)

Goldman, M.; Vlahcevic, Z.R.; Schwartz, C.C.; Gustafsson, J.; Swell, L.

1982-01-01

In order to evaluate more definitively the observed aberrations in the synthesis of cholic and chenodeoxycholic acids in patients with advanced cirrhosis, two bile acid biosynthesis pathways were examined by determining the efficiency of conversion of [ 3 H]7 alpha-hydroxycholesterol and [ 3 H] 26-hydroxycholesterol to primary bile acids. Bile acid kinetics were determined by administration of [ 14 C]cholic and [ 14 C]chenodeoxycholic acids. Cholic acid synthesis in cirrhotic patients was markedly depressed (170 vs 927 μmoles per day)( while chenodeoxycholic acid synthesis was reduced to a much lesser degree (227 vs 550 μmoles per day). The administration of [ 3 H]7 alpha-hydroxycholesterol allowed for an evaluation of the major pathway of bile acid synthesis via the 7 alpha-hydroxylation of cholesterol. This compound was efficiently incorporated into primary bile acids by the two normal subjects (88 and 100%) and two cirrhotic patients (77 and 91%). However, the recovery of the label in cholic acid was slightly less in cirrhotic patients than in normal subjects. [ 3 H]26-hydroxycholesterol was administered to ascertain the contribution of the 26-hydroxylation pathway to bile acid synthesis. All study subjects showed poor conversion (9 to 22%) of this intermediate into bile acids. The results of this study suggest that a major block in the bile acid synthesis pathway in cirrhosis is at the level of 7 alpha-hydroxylation of cholesterol (impairment of 7 alpha-hydroxylase) and/or in the feedback triggering mechanism regulating bile acid synthesis. The data also suggest that the 26-hydroxylation pathway in normal subjects and patients with cirrhosis is a minor contributor to synthesis of the primary bile acids. Therefore, the relative sparing of chenodeoxycholic acid synthesis observed in cirrhotic patients is not due to preferential synthesis of this bile acid via the 26-hydroxylation pathway

A Comparative Study of Effects of Omega‑3 Fatty Acids, Alpha Lipoic ...

African Journals Online (AJOL)

Background: Diabetes Mellitus is a metabolic disorder characterized by abnormal lipid and glucose metabolism. Various modes of adjuvant therapy have been advocated to ameliorate insulin resistance. Aim: This study was intended to assess the effects of antioxidants; alpha lipoic acid (ALA), omega 3 fatty acid and vitamin ...

Bioinspired catalytic generation of high-valent cobalt-oxo species by the axially coordinated CoPc on pyridine-functionalized MWCNTs for the elimination of organic contaminants

Science.gov (United States)

Li, Nan; Wang, Ying; Wu, Chenren; Lu, Wangyang; Pei, Kemei; Chen, Wenxing

2018-03-01

Enzymes have always been a source of inspiration for the design and improvement of catalysts. Many examples are occurring in heme/non-heme metalloenzymes with the generation of active high-valent metal-oxo intermediates that are controlled by the surrounding amino acids/protein and axial residue ligands, facilitating the efficient oxidation of substrates in biochemical processes. Here, the high-valent cobalt-oxo species have been formed during the heterolysis of H2O2 activated by the bioinspired catalyst, axially coordinated cobalt phthalocyanine (CoPc) on pyridine-functionalized multi-walled carbon nanotubes (MWCNTs-Py), characterized by ultraviolet-visible and X-ray photoelectron spectroscopy. Formation process of the active cobalt-oxo species has been further confirmed by electrospray ionization mass spectrometry analysis and the results from the density functional theory (B3LYP/6-311G) calculations. Such high-valent cobalt-oxo species exhibit high reactivity and enough persistence for the oxidation of the target substrate, C.I. Acid Red 1. The oxidation products are nearly biodegradable small molecules identified by ultra-performance liquid chromatography/high-definition mass spectrometry. This strategy provides a foundation on developing efficient and persistent catalytic system, in particular oxidation processes based on the complex catalysts with N4 macrocycle structures.

Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements.

Science.gov (United States)

Mahotka, C; Hansen-Hagge, T E; Bartram, C R

1995-10-01

Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.

Flavonóide e triterpenos de Stigmaphyllom paralias

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David Jorge M.

2003-01-01

Full Text Available Stigmaphyllom paralias is a herb belonging to the family Malpighiaceae that occurs in sand soil of brazilian " restinga". This is the first report regarding phytochemical study with this species. The hexane extract of the aerial parts of plant afforded the triterpenes friedelin, lupenone, 3-oxo-alpha-amirin and 3-oxo-beta-amirin, the mixture of alpha-amirinyl palmitate and stearate, lupeol and 3,4-seco-friedelan-3-oic acid. The AcOEt extract yielded the flavonoid luteolin-7-rutinoside. All compounds were characterized by analysis of spectrometric data and the fatty acids esterified with alpha-amirine were identified by GC/MS of methyl derivatives of transesterified products . This is the first natural occurence of 3,4-seco-friedelan-3-oic acid and the 13C NMR spectral data were inequivocally assigned by two-dimensional techniques. This work also permitted to correct the 13C NMR resonances attributed to methyl groups C-26 and C-27 of fridelin.

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

OpenAIRE

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, suc...

HPLC Analysis of [Alpha]- and [Beta]-Acids in Hops

Science.gov (United States)

Danenhower, Travis M.; Force, Leyna J.; Petersen, Kenneth J.; Betts, Thomas A.; Baker, Gary A.

2008-01-01

Hops have been used for centuries to impart aroma and bitterness to beer. The cones of the female hop plant contain both essential oils, which include many of the fragrant components of hops, and a collection of compounds known as [alpha]- and [beta]-acids that are the precursors to bittering agents. In order for brewers to predict the ultimate…

Bowl adamanzanes-bicyclic tetraamines: syntheses and crystal structures of complexes with cobalt(III) and chelating coordinated oxo-anions

DEFF Research Database (Denmark)

Broge, Louise; Søtofte, Inger; Jensen, Kristian

2007-01-01

complex is provided. Four of the seven complexes contain a chelate coordinating oxo-anion ( sulfate, formiate, nitrate, carbonate). Equilibration of these species with the corresponding diaqua complex is generally slow. The rates of equilibration in 5 mol dm(-3) perchloric acid at 25 degrees C have been...

A Mononuclear Non-Heme Manganese(IV)-Oxo Complex Binding Redox-Inactive Metal Ions

Energy Technology Data Exchange (ETDEWEB)

Chen, Junying; Lee, Yong-Min; Davis, Katherine M.; Wu, Xiujuan; Seo, Mi Sook; Cho, Kyung-Bin; Yoon, Heejung; Park, Young Jun; Fukuzumi, Shunichi; Pushkar, Yulia N.; Nam, Wonwoo [Ewha; (Purdue); (Osaka)

2013-05-29

Redox-inactive metal ions play pivotal roles in regulating the reactivities of high-valent metal–oxo species in a variety of enzymatic and chemical reactions. A mononuclear non-heme Mn(IV)–oxo complex bearing a pentadentate N₅ ligand has been synthesized and used in the synthesis of a Mn(IV)–oxo complex binding scandium ions. The Mn(IV)–oxo complexes were characterized with various spectroscopic methods. The reactivities of the Mn(IV)–oxo complex are markedly influenced by binding of Sc³⁺ ions in oxidation reactions, such as a ~2200-fold increase in the rate of oxidation of thioanisole (i.e., oxygen atom transfer) but a ~180-fold decrease in the rate of C–H bond activation of 1,4-cyclohexadiene (i.e., hydrogen atom transfer). The present results provide the first example of a non-heme Mn(IV)–oxo complex binding redox-inactive metal ions that shows a contrasting effect of the redox-inactive metal ions on the reactivities of metal–oxo species in the oxygen atom transfer and hydrogen atom transfer reactions.

Crystal structures of hibiscus acid and hibiscus acid dimethyl ester isolated from Hibiscus sabdariffa (Malvaceae)

OpenAIRE

Zheoat, Ahmed M.; Gray, Alexander I.; Igoli, John O.; Kennedy, Alan R.; Ferro, Valerie A.

2017-01-01

The biologically active title compounds have been isolated from Hibiscus sabdariffa plants, hibiscus acid as a dimethyl sulfoxide monosolvate [systematic name: (2S,3R)-3-hy?droxy-5-oxo-2,3,4,5-tetra?hydro?furan-2,3-di?carb?oxy?lic acid dimethyl sulfoxide monosolvate], C6H6O7?C2H6OS, (I), and hibiscus acid dimethyl ester [systematic name: dimethyl (2S,3R)-3-hy?droxy-5-oxo-2,3,4,5-tetra?hydro?furan-2,3-di?carboxyl?ate], C8H10O7, (II). Compound (I) forms a layered structure with alternating laye...

Prenatal long-chain polyunsaturated fatty acid status : the importance of a balanced intake of docosahexaenoic acid and arachidonic acid

NARCIS (Netherlands)

Hadders-Algra, Mijna

2008-01-01

This review addresses the effect of prenatal long-chain polyunsaturated fatty acid (LCPUFA) status on neuro-developmental outcome. It focuses on the major LPCUFA doxosahexaenoic acid (DNA; 22:6 omega 3) and arachidonic acid (AA; 20:4 omega 6). Due to enzymatic competition high DHA intake results in

Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

Directory of Open Access Journals (Sweden)

P. Roncada

2010-04-01

Full Text Available Alpha1-acid glycoprotein (AGP is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations. In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far.

A new and concise strategy to the enantioselective synthesis of (S)-2-amino-4-oxo-4-(pyridine-2-yl) butanoic acid from aspartic acid

Energy Technology Data Exchange (ETDEWEB)

Lima, Evanoel Crizanto de; Souza, Carolina C. de; Maior, Marta C.L.S.; Costa, Paulo R.R., E-mail: prrcosta@ism.com.b [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Centro de Ciencias da Saude. Nucleo de Pesquisas de Produtos Naturais; Lima, Paulo G. de [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Quimica; Dias, Ayres G. [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Quimica

2010-07-01

The alpha-amino acid (S)-5 was synthesized using in the key step a chemoselective nucleophilic substitution between a diester derived from L-aspartic acid and 2-lithium pyridine. The overall yield (13%, 5 steps) was similar to those previously described by our group for the R isomer (the first exogen full agonist of the NMDA receptors) from D-mannitol (12%, 10 steps) and by Lovey and Copper for the racemic synthesis (17%, 5 steps). (author)

Effect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Mostafa Jamalan

2015-10-01

Full Text Available Objective: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C and alpha-tocopherol (vitamin E, anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP, insulin, leptin, tumor necrosis factor alpha (TNF-α, and serum amyloid A (SAA in patients with diabetes mellitus type 2. Methods: Male patients (n=80 were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day or alpha-tocopherol (300 mg/day orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared. Results: Our results showed that both ascorbic acid and alpha-tocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alpha-tocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level. Conclusion: Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2.  It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus.

Amylose-dicarboxylic acid inclusion complexes: Characterization and comparison to monocarboxylic acid complexes

Science.gov (United States)

One of the main components in starch, amylose is an essentially linear polymer composed of glucose connected through alpha-1,4-bonds. Amylose is well known to form helical inclusion complexes with various types of ligands such as iodine, medium and long chain fatty acids, alcohols, lactones, and fl...

Dual Effects of Alpha-Hydroxy Acids on the Skin

Directory of Open Access Journals (Sweden)

Sheau-Chung Tang

2018-04-01

Full Text Available AHAs are organic acids with one hydroxyl group attached to the alpha position of the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid are often used extensively in cosmetic formulations. AHAs have been used as superficial peeling agents as well as to ameliorate the appearance of keratoses and acne in dermatology. However, caution should be exercised in relation to certain adverse reactions among patients using products with AHAs, including swelling, burning, and pruritus. Whether AHAs enhance or decrease photo damage of the skin remains unclear, compelling us to ask the question, is AHA a friend or a foe of the skin? The aim of this manuscript is to review the various biological effects and mechanisms of AHAs on human keratinocytes and in an animal model. We conclude that whether AHA is a friend or foe of human skin depends on its concentration. These mechanisms of AHAs are currently well understood, aiding the development of novel approaches for the prevention of UV-induced skin damage.

The role of essential fatty acids in the control of coronary heart disease

DEFF Research Database (Denmark)

Vedtofte, Mia S.; Jakobsen, Marianne U; Lauritzen, Lotte

2012-01-01

Evidence from various research paradigms supports the cardiovascular benefits of a high intake of n-3 polyunsaturated fatty acids (PUFAs), especially the long-chain, marine-derived n-3 PUFA, eicosapentaenoic acids and docosahexaenoic acids. The effect of the plant-derived alpha-linolenic acid (ALA...

CACA-TOCSY with alternate {sup 13}C-{sup 12}C labeling: a {sup 13}C{sup {alpha}} direct detection experiment for mainchain resonance assignment, dihedral angle information, and amino acid type identification

Energy Technology Data Exchange (ETDEWEB)

Takeuchi, Koh [National Institute of Advanced Industrial Science and Technology (AIST), Biomedicinal Information Research Center (BIRC) (Japan); Frueh, Dominique P.; Sun, Zhen-Yu J.; Hiller, Sebastian; Wagner, Gerhard, E-mail: gerhard_wagner@hms.harvard.ed [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States)

2010-05-15

We present a {sup 13}C direct detection CACA-TOCSY experiment for samples with alternate {sup 13}C-{sup 12}C labeling. It provides inter-residue correlations between {sup 13}C{sup {alpha}} resonances of residue i and adjacent C{sup {alpha}s} at positions i - 1 and i + 1. Furthermore, longer mixing times yield correlations to C{sup {alpha}} nuclei separated by more than one residue. The experiment also provides C{sup {alpha}}-to-side chain correlations, some amino acid type identifications and estimates for {psi} dihedral angles. The power of the experiment derives from the alternate {sup 13}C-{sup 12}C labeling with [1,3-{sup 13}C] glycerol or [2-{sup 13}C] glycerol, which allows utilizing the small scalar {sup 3}J{sub CC} couplings that are masked by strong {sup 1}J{sub CC} couplings in uniformly {sup 13}C labeled samples.

A Catalase-related Hemoprotein in Coral Is Specialized for Synthesis of Short-chain Aldehydes: DISCOVERY OF P450-TYPE HYDROPEROXIDE LYASE ACTIVITY IN A CATALASE.

Science.gov (United States)

Teder, Tarvi; Lõhelaid, Helike; Boeglin, William E; Calcutt, Wade M; Brash, Alan R; Samel, Nigulas

2015-08-07

In corals a catalase-lipoxygenase fusion protein transforms arachidonic acid to the allene oxide 8R,9-epoxy-5,9,11,14-eicosatetraenoic acid from which arise cyclopentenones such as the prostanoid-related clavulones. Recently we cloned two catalase-lipoxygenase fusion protein genes (a and b) from the coral Capnella imbricata, form a being an allene oxide synthase and form b giving uncharacterized polar products (Lõhelaid, H., Teder, T., Tõldsepp, K., Ekins, M., and Samel, N. (2014) PloS ONE 9, e89215). Here, using HPLC-UV, LC-MS, and NMR methods, we identify a novel activity of fusion protein b, establishing its role in cleaving the lipoxygenase product 8R-hydroperoxy-eicosatetraenoic acid into the short-chain aldehydes (5Z)-8-oxo-octenoic acid and (3Z,6Z)-dodecadienal; these primary products readily isomerize in an aqueous medium to the corresponding 6E- and 2E,6Z derivatives. This type of enzymatic cleavage, splitting the carbon chain within the conjugated diene of the hydroperoxide substrate, is known only in plant cytochrome P450 hydroperoxide lyases. In mechanistic studies using (18)O-labeled substrate and incubations in H2(18)O, we established synthesis of the C8-oxo acid and C12 aldehyde with the retention of the hydroperoxy oxygens, consistent with synthesis of a short-lived hemiacetal intermediate that breaks down spontaneously into the two aldehydes. Taken together with our initial studies indicating differing gene regulation of the allene oxide synthase and the newly identified catalase-related hydroperoxide lyase and given the role of aldehydes in plant defense, this work uncovers a potential pathway in coral stress signaling and a novel enzymatic activity in the animal kingdom. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Synthesis, spectroscopic and DFT studies of novel 4-(morpholinomethyl)-5-oxo-1-phenylpyrrolidine-3-carboxylic acid

Science.gov (United States)

Devi, Poornima; Fatma, Shaheen; Bishnoi, Abha; Srivastava, Krishna; Shukla, Shraddha; Kumar, Roop

2018-04-01

A novel 4-(morpholinomethyl)-5-oxo-1-phenylpyrrolidine-3-carboxylic acid has been synthesized and its structural elucidation has been done by UV, FT-IR, 1H and 13C NMR spectroscopy. All quantum chemical calculations were carried out at level of density functional theory (DFT) with B3LYP function using 6-31G (d, p) basis atomic set. AIM approach has been incorporated for the analysis of various intermolecular interactions. Polarizability and hyperpolarizabilities values have been calculated along with the exploration of nonlinear optical properties of the title compound. DFT computed total first static hyperpolarizability (β0 = 0.2747 × 10-30 esu) indicates that title molecule could be an area of interest as an attractive future NLO material. For the analysis of thermal behaviour of title molecule, thermodynamic properties such as heat capacity, entropy and enthalpy change at various temperatures have been calculated. The NBO computations were done for the correlation of possible transitions with the electronic transitions. Electrophilic and nucleophilic regions were identified with the help of MESP plot. Determination of energy gap has been done by using HOMO and LUMO energy values, along with the computation of electronegativity and electrophilicity indices.

Whole-body nitrogen and tyrosine metabolism in surgical patients receiving branched-chain amino acid solutions

International Nuclear Information System (INIS)

Desai, S.P.; Bistrian, B.R.; Moldawer, L.L.; Blackburn, G.L.

1985-01-01

Fifteen patients undergoing gastric bypass surgery for morbid obesity received preoperatively a standard crystalline amino acid solution containing 15.6% branched-chain amino acids. During the first five postoperative days, the patients were randomized to receive one of three amino acid solutions of different branched-chain amino acid content. Whole-body amino acid appearance and oxidation were estimated using a continuous intravenous infusion of L-(U- 14 C)-tyrosine preoperatively and on the third postoperative day. This study suggests that an adequate nitrogen intake of a balanced amino acid mixture, as well as a solution enriched with branched-chain amino acids, maintains protein homeostasis and supports protein synthesis similarly in well-nourished patients following major abdominal surgery. A diet containing only branched-chain amino acids in isomolar ratios was as effective at maintaining protein retention and whole-body protein synthesis and albumin renewal postoperatively when compared with a standard amino acid formula

Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress.

Science.gov (United States)

Liu, Tingting; Duan, Wang; Nizigiyimana, Paul; Gao, Lin; Liao, Zhouning; Xu, Boya; Liu, Lerong; Lei, Minxiang

2018-02-05

Diabetic nephropathy is a common complication of diabetes, but there are currently few treatment options. The aim of this study was to gain insight into the effect of alpha-mangostin on diabetic nephropathy and possible related mechanisms. Goto-Kakizaki rats were used as a diabetic model and received alpha-mangostin or desipramine treatment with normal saline as a control. Ten age-matched Sprague Dawley rats were used as normal controls and treated with normal saline. At week 12, blood glucose, albuminuria, apoptosis and renal pathologic changes were assessed. Protein levels for acid sphingomyelinase, glucose-regulated protein 78, phosphorylated PKR-like ER-resident kinase, activated transcription factor 4, CCAAT/enhancer-binding protein, homologous protein), and cleaved-caspase12 were measured. The level of acid sphingomyelinase was significantly increased, and ER stress was activated in diabetic rat kidneys when compared to the control animals. When acid sphingomyelinase was inhibited by alpha-mangostin, the expression of ER stress-related proteins was down-regulated in association with decreased levels of diabetic kidney injury. Alpha-mangostin, an acid sphingomyelinase inhibitor plays a protective role in diabetic neuropathy by relieving ER stress induced-renal cell apoptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of ascorbic acid on in vivo amidation of alpha-melanocyte stimulating hormone in guinea pig pituitary

DEFF Research Database (Denmark)

Fenger, M; Hilsted, L

1988-01-01

The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (alpha MSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 +/- 0.11 mumol/g tissue (mean +/- SD) in the pituitary and 0.34 +/- 0.07 mumol......-39) immunoreactivity was observed in the depleted guinea pigs. Gel chromatography and reversed-phase high-performance luquid chromatography showed that the alpha MSH and ACTH (1-14) immunoreactivity was of low molecular weight and partly mono- or diacetylated. Depletion of ascorbic acid had no influence on the degree...... of acetylation of alpha MSH and ACTH (1-14). It is concluded that depletion of ascorbic acid reduces the in vivo amidation of ACTH (1-14) in the guinea pig pituitary....

Alternate method of source preparation for alpha spectrometry: No electrodeposition, no hydrofluoric acid

International Nuclear Information System (INIS)

Kurosaki, Hiromu; Mueller, Rebecca J.; Lambert, Susan B.; Rao, Govind R.

2016-01-01

An alternate method of preparing actinide alpha counting sources was developed in place of electrodeposition or lanthanide fluoride micro-precipitation. The method uses lanthanide hydroxide micro-precipitation to avoid the use of hazardous hydrofluoric acid. Lastly, it provides a quicker, simpler, and safer way of preparing actinide alpha counting sources in routine, production-type laboratories that process many samples daily.

Alternate method of source preparation for alpha spectrometry: no electrodeposition, no hydrofluoric acid

International Nuclear Information System (INIS)

Hiromu Kurosaki; Lambert, S.B.; Rao, G.R.; Mueller, R.J.

2017-01-01

An alternate method of preparing actinide alpha counting sources was developed in place of electrodeposition or lanthanide fluoride micro-precipitation. The method uses lanthanide hydroxide micro-precipitation to avoid the use of hazardous hydrofluoric acid. It provides a quicker, simpler, and safer way of preparing actinide alpha counting sources in routine, production-type laboratories that process many samples daily. (author)

Effect of Difference in Fatty Acid Chain Lengths of Medium- Chain Lipids on Lipid/Surfactant/Water Phase Diagrams and Drug Solubility

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Hetal N. Prajapati

2011-09-01

Full Text Available Lipids consisting of medium chain fatty acids are commonly used in the development of lipid-based selfemulsifying and self-microemulsifying drug delivery systems. However, no systematic approach to selecting one lipid over another has been reported in the literature. In this study, propylene glycol (PG monoester (PG monocaprylate, Capmul PG-8® and PG diester (PG dicaprylocaprate, Captex 200P® of C8-fatty acids were compared with PG monoester (PG monolaurate, Capmul PG-12® and PG diester (PG dilaurate, Capmul PG-2L® of C12-fatty acids with respect to their phase diagrams, and especially for their ability to form microemulsions in the presence of a common surfactant, Cremophor EL®, and water. The solubility of two model drugs, danazol and probucol, in the lipids and lipid/surfactant mixtures were also compared. The effect of the chain length of medium-chain fatty acids (C8 versus C12 on the phase diagrams of the lipids was minimal. Both shorter and longer chain lipids formed essentially similar microemulsion and emulsion regions in the presence of Cremophor EL® and water, although the C12-fatty acid esters formed larger gel regions in the phase diagrams than the C8-fatty acid esters. When monoesters were mixed with their respective diesters at 1:1 ratios, larger microemulsion regions with lower lipid particle sizes were observed compared to those obtained with individual lipids alone. While the solubility of both danazol and probucol increased greatly in all lipids studied, compared to their aqueous solubility, the solubility in C12-fatty acid esters was found to be lower than in C8-fatty acid esters when the lipids were used alone. This difference in solubility due to the difference in fatty acid chain length, practically disappeared when the lipids were combined with the surfactant.

Effects of L-ascorbic acid and alpha-tocopherol on biochemical ...

African Journals Online (AJOL)

Background: The purpose of this study is to determine the effect of L-ascorbic acid and alpha-tocopherol as well as combination of these vitamins with or without exposure to physical exercise on intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and ...

Main chain acid-degradable polymers for the delivery of bioactive materials

Science.gov (United States)

Frechet, Jean M. J. [Oakland, CA; Standley, Stephany M [Evanston, IL; Jain, Rachna [Milpitas, CA; Lee, Cameron C [Cambridge, MA

2012-03-20

Novel main chain acid degradable polymer backbones and drug delivery systems comprised of materials capable of delivering bioactive materials to cells for use as vaccines or other therapeutic agents are described. The polymers are synthesized using monomers that contain acid-degradable linkages cleavable under mild acidic conditions. The main chain of the resulting polymers readily degrade into many small molecules at low pH, but remain relatively stable and intact at physiological pH. The new materials have the common characteristic of being able to degrade by acid hydrolysis under conditions commonly found within the endosomal or lysosomal compartments of cells thereby releasing their payload within the cell. The materials can also be used for the delivery of therapeutics to the acidic regions of tumors and other sites of inflammation.

Uranyl oxo activation and functionalization by metal cation coordination

International Nuclear Information System (INIS)

Arnold Polly, L.; Pecharman, A. F.; Hollis, E.; Parsons, S.; Love, J. B.; Yahia, A.; Maron, L.; Yahia, A.; Maron, L.

2010-01-01

The oxo groups in the uranyl ion [UO 2 ] 2+ - one of many oxo cations formed by metals from across the periodic table - are particularly inert, which explains the dominance of this ion in the laboratory and its persistence as an environmental contaminant. In contrast, transition metal oxo (M=O) compounds can be highly reactive and carry out difficult reactions such as the oxygenation of hydrocarbons. Here we show how the sequential addition of a lithium metal base to the uranyl ion constrained in a 'Pacman' environment results in lithium coordination to the U=O bonds and single-electron reduction. This reaction depends on the nature and stoichiometry of the lithium reagent and suggests that competing reduction and C-H bond activation reactions are occurring. (authors)

Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis.

Science.gov (United States)

Hayashi, T; Kawasaki, M; Okamura, K; Tamada, Y; Morita, N; Tezuka, Y; Kikuchi, T; Miwa, Y; Taga, T

1992-12-01

The 70% EtOH extract of Scoparia dulcis showed inhibitory activity against beta-glucuronidase from bovine liver. Bioassay-directed fractionation of the active extract led to the isolation of three labdane-type diterpene acids, scoparic acid A [1] [6-benzoyl-12-hydroxy-labda-8(17), 13-dien-18-oic acid], scoparic acid B [2] [6-benzoyl-14,15-dinor-13-oxo-8(17)-labden-18-oic acid], and scoparic acid C [3] [6-benzoyl-15-nor-14-oxo-8(17)-labden-18-oic acid], the structures of which were established by spectral means, including X-ray analysis. Scoparic acid A was found to be a potent beta-glucuronidase inhibitor.

Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.

Science.gov (United States)

Bourre, J M

2004-01-01

Among various organs, in the brain, the fatty acids most extensively studied are omega-3 fatty acids. Alpha-linolenic acid (18:3omega3) deficiency alters the structure and function of membranes and induces minor cerebral dysfunctions, as demonstrated in animal models and subsequently in human infants. Even though the brain is materially an organ like any other, that is to say elaborated from substances present in the diet (sometimes exclusively), for long it was not accepted that food can have an influence on brain structure, and thus on its function. Lipids, and especially omega-3 fatty acids, provided the first coherent experimental demonstration of the effect of diet (nutrients) on the structure and function of the brain. In fact the brain, after adipose tissue, is the organ richest in lipids, whose only role is to participate in membrane structure. First it was shown that the differentiation and functioning of cultured brain cells requires not only alpha-linolenic acid (the major component of the omega-3, omega3 family), but also the very long omega-3 and omega-6 carbon chains (1). It was then demonstrated that alpha-linolenic acid deficiency alters the course of brain development, perturbs the composition and physicochemical properties of brain cell membranes, neurones, oligodendrocytes, and astrocytes (2). This leads to physicochemical modifications, induces biochemical and physiological perturbations, and results in neurosensory and behavioural upset (3). Consequently, the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for infants (premature and term) conditions the visual and cerebral abilities, including intellectual. Moreover, dietary omega-3 fatty acids are certainly involved in the prevention of some aspects of cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, notably Alzheimer's disease. Recent

Molecular and crystal structure of 3,4-dihydroxy-2-oxo-1-methyl-4-phenylpiperidine

International Nuclear Information System (INIS)

Kuleshova, L.N.; Khrustalev, V.N.; Struchkov, Yu.T.; Soldatenkov, A.T.; Bekro, I.A.; Mamyrbekova, Zh.A.; Soldatova, S.A.

1996-01-01

The molecular and crystal structure of 3,4-dihydroxy-2-oxo-1-methyl-4-phenylpiperidine was determined. The crystal is orthorhombic: sp. gr. Pca21; a=15.764, b=5.635, and c=25.536 A; and Z=8. The structure was solved by direct methods; R1=0.051, for 2643 unique refections. Symmetry-independent molecules are related by a pseudocenter of symmetry. The piperidine cycle has an asymmetric half-chair conformation. The orientation of substituents is determined. In the crystal, intermolecular OH...O hydrogen bonds link the molecules into chains parallel to the Y-axis

Tetranuclear copper(II) complexes bridged by alpha-D-glucose-1-phosphate and incorporation of sugar acids through the Cu4 core structural changes.

Science.gov (United States)

Kato, Merii; Sah, Ajay Kumar; Tanase, Tomoaki; Mikuriya, Masahiro

2006-08-21

-D-gluconolactone, D-glucuronic acid, or D-glucaric acid in dimethylformamide resulted in the formation of discrete tetracopper complexes with sugar acids, [Cu4{mu-(alpha-D-Glc-1P)}2(mu-SA)2(bpy)4](NO3)2 [SA = D-gluconate (6), D-glucuronate (7), D-glucarateH (8a)]. The structures of 6 and 7 were determined by X-ray crystallography to be almost identical with that of 3 with additional chelating coordination of the C-2 hydroxyl group of D-gluconate moieties (6) or the C-5 cyclic O atom of D-glucuronate units (7). Those with D-glucaric acid and D-lactobionic acid afforded chiral one-dimensional polymers, {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-glucarate)(bpy)4](NO3)2}n (8b) and {[Cu4{mu-(alpha-D-Glc-1P)}2(mu-D-lactobionate)(bpy)4(H2O)2](NO3)3}n (9), respectively, in which the D-Glc-1P-bridged tetracopper(II) units are connected by sugar acid moieties through the C-1 and C-6 carboxylate O atoms in 8b and the C-1 carboxylate and C-6 alkoxy O atoms of the gluconate chain in 9. When complex 7 containing d-glucuronate moieties was heated in water, the mononuclear copper(II) complex with 2-dihydroxy malonate, [Cu(mu-O2CC(OH)2CO2)(bpy)] (10), and the dicopper(II) complex with oxalate, [Cu2(mu-C2O4)(bpy)2(H2O)2](NO3)2 (11), were obtained as a result of oxidative degradation of the carbohydrates through C-C bond cleavage reactions.

Improved synthesis with high yield and increased molecular weight of poly(alpha,beta-malic acid) by direct polycondensation.

Science.gov (United States)

Kajiyama, Tetsuto; Kobayashi, Hisatoshi; Taguchi, Tetsushi; Kataoka, Kazunori; Tanaka, Junzo

2004-01-01

The development of synthetic biodegradable polymers, such as poly(alpha-hydroxy acid), is particularly important for constructing medical devices, including scaffolds and sutures, and has attracted growing interest in the biomedical field. Here, we report a novel approach to preparing high molecular weight poly(malic acid) (HMW--PMA) as a biodegradable and bioabsorbable water-soluble polymer. We investigated in detail the reaction conditions for the simple direct polycondensation of l-malic acid, including the reaction times, temperatures, and catalysts. The molecular weight of synthesized alpha,beta-PMA is dependent on both the reaction temperature and time. The optimum reaction condition to obtain alpha,beta-PMA by direct polycondensation using tin(II) chloride as a catalyst was thus determined to be 110 degrees C for 45 h with a molecular weight of 5300. The method for alpha,beta-PMA synthesis established here will facilitate production of alpha,beta-PMA of various molecular weights, which may have a potential utility as biomaterials.

Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients

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Rino A Gani

2016-05-01

Full Text Available Aim: to evaluate the use of alpha-1-acid glycoprotein (AAG for diagnosing hepatocellular carcinoma (HCC, and to combine with alpha fetoprotein (AFP as part of routine examination in liver cirrhosis patients. Methods: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA. Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach in HCC cases. Results: receiver operating characteristic (ROC analysis showed that area under the curve for AFP AAG combination was 88.1% and higher than AFP only (86.2% or AAG only (76.5% with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. Conclusion: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC. Key words: alpha fetoprotein, alpha-1-acid glycoprotein, biomarker, liver cancer

Syntheses, structures, and photoluminescence of lanthanide coordination polymers based on 4-oxo-1,4-dihydro-2,6-pyridinedicarboxylic acid

Energy Technology Data Exchange (ETDEWEB)

Qian, Jing; Li, Lei; Peng, Jing-Wei; Qiao, Wei-Wei; Sun, Mei-Mei [College of Chemistry, Tianjin Normal University, Tianjin (China); Gu, Wen [College of Chemistry, Nankai University, Tianjin (China)

2018-03-15

Investigating the coordination chemistry of H{sub 2}CDA (4-oxo-1,4-dihydro-2,6-pyridinedicarboxylic acid) with rare earth salts Ln(NO{sub 3}){sub 3} under hydrothermal conditions, structure transformation phenomenon was observed. The ligand, H{sub 2}CDA charged to its position isomer, enol type structure, H{sub 3}CAM (4-hydroxypyridine-2,6-dicarboxylic acid). Six new lanthanide(III) coordination polymers with the formulas [Ln(CAM)(H{sub 2}O){sub 3}]{sub n} [Ln = La (1), Pr, (2)] and {[Ln(CAM)(H_2O)_3].H_2O}{sub n} [Ln = Nd, (3), Sm, (4), Eu, (5), Y, (6)] were synthesized and characterized. The X-ray structure analyses show two kinds of coordination structures. The complexes 1 and 2 and 3-6 are isostructural. Complexes 1 and 2 crystallize in the monoclinic C{sub 2}/c space group, whereas 3-6 crystallize in the monoclinic system with space group P2{sub 1}/n. In the two kinds of structures, H{sub 3}CAM displays two different coordination modes. The Sm{sup III} and Eu{sup III} complexes exhibit the corresponding characteristic luminescence in the visible region at an excitation of 376 nm. (copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

CONTENT OF LONG CHAIN OMEGA-3 FATTY ACID COMPOSITION IN SOME IRANIAN CANNED FISH

Directory of Open Access Journals (Sweden)

Bahar Nazari

2010-12-01

Full Text Available Abstract    BACKGROUND: Ecological studies have found a negative correlation between the risk of developing heart disease and fish consumption because of their long chain omega-3 fatty acids. This study was undertaken to determine the amounts of the common fatty acid content of several commercial canned fish marketing in Iran, with particular attention to long chain omega-3 fatty acids.    METHODS: The most consumed available brands of canned fish were randomly selected seven times from products available in supermarkets. Total lipids were extracted by using the Folch method and prepared for fatty acid analysis. Individual fatty acids were quantified by gas chromatography (GC with 60 meter capillary column and flame ionization detector.    RESULTS: The most common saturated fatty acids (SFA in Iranian canned fish was palmitic acid (C16:0 followed by stearic acid (C18:0. The amount of all trans fatty acids (TFAs except elaidic acid (C18:1 9t was 0%. The highest amount of polyunsaturated fatty acids (PUFAs related to long chain omega-3 fatty acids include eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. The most abundant monounsaturated fatty acids (MUFAs were oleic acid (C18:1 9c.     CONCLUSION: This study showed higher contents of EPA and DHA in Iranian commercially available canned fish compared to the canned fish in other countries.      Keywords: Iranian canned fish, fatty acids, long chain omega-3 fatty acids, gas chromatography.  

Comparative Genomics of Regulation of Fatty Acid and Branched-chain Amino Acid Utilization in Proteobacteria

Energy Technology Data Exchange (ETDEWEB)

Kazakov, Alexey E.; Rodionov, Dmitry A.; Arkin, Adam Paul; Dubchak, Inna; Gelfand, Mikhail S.; Alm, Eric

2008-10-31

Bacteria can use branched-chain amino acids (ILV, i.e. isoleucine, leucine, valine) and fatty acids (FA) as sole carbon and energy sources convering ILV into acetyl-CoA, propanoyl-CoA and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR and GntR families binding to eleven distinct DNA motifs. The ILV degradation genes in gamma- and beta-proteobacteria are mainly regulated by anovel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species), in addition, the TetR-type regulator LiuQ was identified in some beta-proteobacteria (8 species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in the Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gamma-proteobacteria (34 species), PsrA in gamma- and beta-proteobacteria (45 species), FadP in beta-proteobacteria (14 species), and LiuR orthologs in alpha-proteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from the functional and evolutionary points of view.

A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids.

Science.gov (United States)

Zheng, Xiaojiao; Qiu, Yunping; Zhong, Wei; Baxter, Sarah; Su, Mingming; Li, Qiong; Xie, Guoxiang; Ore, Brandon M; Qiao, Shanlei; Spencer, Melanie D; Zeisel, Steven H; Zhou, Zhanxiang; Zhao, Aihua; Jia, Wei

2013-08-01

Research in obesity and metabolic disorders that involve intestinal microbiota demands reliable methods for the precise measurement of the short-chain fatty acids (SCFAs) and branched-chain amino acids (BCAAs) concentration. Here, we report a rapid method of simultaneously determining SCFAs and BCAAs in biological samples using propyl chloroformate (PCF) derivatization followed by gas chromatography mass spectrometry (GC-MS) analysis. A one-step derivatization using 100 µL of PCF in a reaction system of water, propanol, and pyridine (v/v/v = 8:3:2) at pH 8 provided the optimal derivatization efficiency. The best extraction efficiency of the derivatized products was achieved by a two-step extraction with hexane. The method exhibited good derivatization efficiency and recovery for a wide range of concentrations with a low limit of detection for each compound. The relative standard deviations (RSDs) of all targeted compounds showed good intra- and inter-day (within 7 days) precision (< 10%), and good stability (< 20%) within 4 days at room temperature (23-25 °C), or 7 days when stored at -20 °C. We applied our method to measure SCFA and BCAA levels in fecal samples from rats administrated with different diet. Both univariate and multivariate statistics analysis of the concentrations of these target metabolites could differentiate three groups with ethanol intervention and different oils in diet. This method was also successfully employed to determine SCFA and BCAA in the feces, plasma and urine from normal humans, providing important baseline information of the concentrations of these metabolites. This novel metabolic profile study has great potential for translational research.

Structural consequences of amino acid substitutions causing Tay-Sachs disease.

Science.gov (United States)

Ohno, Kazuki; Saito, Seiji; Sugawara, Kanako; Sakuraba, Hitoshi

2008-08-01

To determine the structural changes in the alpha-subunit of beta-hexosaminidase due to amino acid substitutions causing Tay-Sachs disease, we built structural models of mutant alpha-subunits resulting from 33 missense mutations (24 infantile and 9 late-onset), and analyzed the influence of each amino acid replacement on the structure by calculating the number of atoms affected and determining the solvent-accessible surface area of the corresponding amino acid residue in the wild-type alpha-subunit. In the infantile Tay-Sachs group, the number of atoms influenced by a mutation was generally larger than that in the late-onset Tay-Sachs group in both the main chain and the side chain, and residues associated with the mutations found in the infantile Tay-Sachs group tended to be less solvent-accessible than those in the late-onset Tay-Sachs group. Furthermore, color imaging determined the distribution and degree of the structural changes caused by representative amino acid substitutions, and that there were also differences between the infantile and late-onset Tay-Sachs disease groups. Structural study is useful for elucidating the basis of Tay-Sachs disease.

Regulation of valine and. alpha. -ketoisocaproate metabolism in rat kidney mitochondria

Energy Technology Data Exchange (ETDEWEB)

Miller, R.H.; Harper, A.E. (Univ. of Wisconsin, Madison (USA))

1988-10-01

Activities of branched-chain amino acid (BCAA) aminotransferase (BCAT) and {alpha}-keto acid dehydrogenase (BCKD) were assayed in mitochondria isolated from kidneys of rats. Rates of transamination of valine and oxidation of keto acids {alpha}-ketoisocaproate (KIC) or {alpha}-ketoisovalerate (KIV) were estimated using radioactive tracers of the appropriate substrate from amounts of {sup 14}C-labeled products formed. Because of the high mitochondrial BCAT activity, an amino acceptor for BCAT, {alpha}-ketoglutarate ({alpha}-KG) or KIC, was added to the assay medium when valine was the substrate. Rates of valine transamination and subsequent oxidation of the KIV formed were determined with 0.5 mM {alpha}-KG as the amino acceptor; these rates were 5- to 50-fold those without added {alpha}-KG. Rates of CO{sub 2} evolution from valine also increased when KIC was present; however, with KIC concentrations above 0.2 mM, rates of CO{sub 2} evolution from valine declined although rates of transamination continued to rise. When 0.05 mM KIC was added to the assay medium, oxidation of KIC was suppressed by inclusion of valine or glutamate in the medium. When valine was present KIC was not oxidized preferentially, presumably because it was also serving as an amino acceptor for BCAT. These results indicate that as the supply of amino acceptor, {alpha}-KG or KIC, is increased in mitochondria not only is the rate of valine transamination stimulated but also the rate of oxidation of the KIV formed from valine. Thus the rate of oxidation of BCAA can be controlled by factors that influence the rate and direction of BCAA transamination and, thereby, the supply of substrate for BCKD.

The effect of increased branched-chain amino acid transaminase activity in yeast on the production of higher alcohols and on the flavour profiles of wine and distillates.

Science.gov (United States)

Lilly, Mariska; Bauer, Florian F; Styger, Gustav; Lambrechts, Marius G; Pretorius, Isak S

2006-08-01

In Saccharomyces cerevisiae, branched-chain amino acid transaminases (BCAATases) are encoded by the BAT1 and BAT2 genes. BCAATases catalyse the transfer of amino groups between those amino acids and alpha-keto-acids. alpha-Keto-acids are precursors for the biosynthesis of higher alcohols, which significantly influence the aroma and flavour of yeast-derived fermentation products. The objective of this study was to investigate the influence of BAT-gene expression on general yeast physiology, on aroma and flavour compound formation and on the sensory characteristics of wines and distillates. For this purpose, the genes were overexpressed and deleted in a laboratory strain, BY4742, and overexpressed in an industrial wine yeast strain, VIN13. The data show that, with the exception of a slow growth phenotype observed for the BAT1 deletion strain, the fermentation behaviour of the strains was unaffected by the modifications. The chemical and sensory analysis of fermentation products revealed a strong correction between BAT gene expression and the formation of many aroma compounds. The data suggest that the adjustment of BAT gene expression could play an important role in assisting winemakers in their endeavour to produce wines with specific flavour profiles.

Effects of alpha-lipoic acids on sperm membrane integrity during liquid storage of boar semen

Directory of Open Access Journals (Sweden)

Laura Parlapan

2015-05-01

Full Text Available Preliminary studies have shown that sperm membrane from swine shows high sensitivity to cryopreservation process, causing a dramatic reduction in sperm quality. This has been attributed to the production of reactive oxygen species, that cause lipid peroxidation in sperm membranes. The aim of the present study was to minimize the oxidative attack by adding different concentration of alpha-lipoic acid into the sperm liquid storage at 17ºC for 7 days. Freshly ejaculated boar semen was diluted with Beltsville Thawing Solution (BTS and supplemented with 5 levels of alpha-lipoic  acid (0.015, 0.02, 0.05, 0.1, 0.15 mmol/ml. The membrane integrity was evaluated at days 0, 1, 3, 5 and 7 of liquid preservation, using flow cytometer FACSCanto II (BD Biociencias systems. The experiment indicate that supplementation of alpha-lipoic  acid to the semen liquid storage extender improve sperm membrane

A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging.

Science.gov (United States)

Magata, Yasuhiro; Kawaguchi, Takayoshi; Ukon, Misa; Yamamura, Norio; Uehara, Tomoya; Ogawa, Kazuma; Arano, Yasushi; Temma, Takashi; Mukai, Takahiro; Tadamura, Eiji; Saji, Hideo

2004-01-01

C-11- and I-123-labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for the estimation of myocardial fatty acid metabolism. We have reported that Tc-99m-labeled N-[[[(2-mercaptoethyl)amino]carbonyl]methyl]-N-(2-mercaptoethyl)-6-aminohexanoic acid ([(99m)Tc]MAMA-HA), a medium chain fatty acid derivative, is metabolized by beta-oxidation in the liver and that the MAMA ligand is useful for attaching to the omega-position of fatty acid derivatives as a chelating group for Tc-99m. On the basis of these findings, we focused on developing a Tc-99m-labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. In this study, we synthesized a dodecanoic acid derivative, MAMA-DA, and a hexadecanoic acid derivative, MAMA-HDA, and performed radiolabeling and biodistribution studies. [(99m)Tc]MAMA-DA and [(99m)Tc]MAMA-HDA were prepared using a ligand-exchange reaction. Biodistribution studies were carried out in normal mice and rats. Then, a high initial uptake of Tc-99m was observed, followed by a rapid clearance from the heart. The maximum heart/blood ratio was 3.6 at 2 min postinjection of [(99m)Tc]MAMA-HDA. These kinetics were similar to those with postinjection of p-[(125)I]iodophenylpentadecanoic acid. Metabolite analysis showed [(99m)Tc]MAMA-HDA was metabolized by beta-oxidation in the body. In conclusion, [(99m)Tc]MAMA-HDA is a promising compound as a long chain fatty acid analogue for estimating beta-oxidation of fatty acid in the heart.

Uranyl oxo activation and functionalization by metal cation coordination

Energy Technology Data Exchange (ETDEWEB)

Arnold Polly, L; Pecharman, A F; Hollis, E; Parsons, S; Love, J B [Univ Edinburgh, EaStCHEM Sch Chem, Edinburgh EH9 3JJ, Midlothian (United Kingdom); Yahia, A; Maron, L [Univ Toulouse 3, LPCNO, UMR 5215, INSA, CNRS, F-31077 Toulouse 4 (France); Yahia, A; Maron, L [Univ Montpellier 2, ENSCM, CNRS, ICSM, UMR 5257, CEA, Ctr Marcoule, F-30207 Bagnols Sur Ceze (France)

2010-07-01

The oxo groups in the uranyl ion [UO{sub 2}]{sup 2+} - one of many oxo cations formed by metals from across the periodic table - are particularly inert, which explains the dominance of this ion in the laboratory and its persistence as an environmental contaminant. In contrast, transition metal oxo (M=O) compounds can be highly reactive and carry out difficult reactions such as the oxygenation of hydrocarbons. Here we show how the sequential addition of a lithium metal base to the uranyl ion constrained in a 'Pacman' environment results in lithium coordination to the U=O bonds and single-electron reduction. This reaction depends on the nature and stoichiometry of the lithium reagent and suggests that competing reduction and C-H bond activation reactions are occurring. (authors)

The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

Directory of Open Access Journals (Sweden)

Ahmet Ali Tuncer

2016-01-01

Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

Degradation of amino acids to short-chain fatty acids in humans. An in vitro study

DEFF Research Database (Denmark)

Rasmussen, H S; Holtug, K; Mortensen, P B

1988-01-01

Short-chain fatty acids (SCFA) originate mainly in the colon through bacterial fermentation of polysaccharides. To test the hypothesis that SCFA may originate from polypeptides as well, the production of these acids from albumin and specific amino acids was examined in a faecal incubation system....... Albumin was converted to all C2-C5-fatty acids, whereas amino acids generally were converted to specific SCFA, most often through the combination of a deamination and decarboxylation of the amino acids, although more complex processes also took place. This study indicates that a part of the intestinal...

Preparation and properties of a monomeric Mn(IV)-oxo complex.

Science.gov (United States)

Parsell, Trenton H; Behan, Rachel K; Green, Michael T; Hendrich, Michael P; Borovik, A S

2006-07-12

Manganese-oxo complexes have long been investigated because of their proposed roles in biological and chemical catalysis. However, there are few examples of monomeric complexes with terminal oxo ligands, especially those with oxomanganese(IV) units. A oxomanganese(IV) complex has been prepared from [MnIIIH3buea(O)]2- ([H3buea]3-, tris[(N'-tert-butylureaylato)-N-ethylene]aminato), a monomeric MnIII-O complex in which the oxo ligand arises from cleavage of dioxygen. Treating [MnIIIH3buea(O)]2- with [Cp2Fe]BF4 in either DMF at -45 degrees C or DMSO at room temperature produces [MnIVH3buea(O)]-: lambdamax = 635 nm; nu(Mn-16O) = 737 cm-1; nu(Mn-18O) = 709 cm-1; g = 5.15, 2.44, 1.63, D = 3.0 cm-1, E/D = 0.26, aMn = 66 G (A = 190 MHz). These spectroscopic properties support the assignment of a mononuclear MnIV-oxo complex with an S = 3/2 ground state. Density functional theory supports this assignment and the Jahn-Teller distortion around the high-spin MnIV center that would alter the molecular structure of [MnIVH3buea(O)]- from trigonal symmetry (as indicated by the highly rhombic EPR signal). [MnIVH3buea(O)]- is relatively unstable in DMSO, converting to [MnIIIH3buea(OH)]- via a proposed X-H bond cleavage. [MnIVH3buea(O)]- reacts with 1,2-diphenylhydrazine to from azobenzene (95% yield) and [MnIIIH3buea(OH)]-. The MnIV-oxo does not react with triphenyl- or tricyclohexylphosphine. However, O-atom transfer is observed with methyldiphenylphosphine and dimethylphenylphosphine, producing the corresponding phosphine oxides. These results illustrate the diverse reactivity of the MnIV-oxo unit.

Structural and Thermodynamic Basis for Weak Interactions between Dihydrolipoamide Dehydrogenase and Subunit-binding Domain of the Branched-chain [alpha]-Ketoacid Dehydrogenase Complex

Energy Technology Data Exchange (ETDEWEB)

Brautigam, Chad A.; Wynn, R. Max; Chuang, Jacinta L.; Naik, Mandar T.; Young, Brittany B.; Huang, Tai-huang; Chuang, David T. (AS); (UTSMC)

2012-02-27

The purified mammalian branched-chain {alpha}-ketoacid dehydrogenase complex (BCKDC), which catalyzes the oxidative decarboxylation of branched-chain {alpha}-keto acids, is essentially devoid of the constituent dihydrolipoamide dehydrogenase component (E3). The absence of E3 is associated with the low affinity of the subunit-binding domain of human BCKDC (hSBDb) for hE3. In this work, sequence alignments of hSBDb with the E3-binding domain (E3BD) of the mammalian pyruvate dehydrogenase complex show that hSBDb has an arginine at position 118, where E3BD features an asparagine. Substitution of Arg-118 with an asparagine increases the binding affinity of the R118N hSBDb variant (designated hSBDb*) for hE3 by nearly 2 orders of magnitude. The enthalpy of the binding reaction changes from endothermic with the wild-type hSBDb to exothermic with the hSBDb* variant. This higher affinity interaction allowed the determination of the crystal structure of the hE3/hSBDb* complex to 2.4-{angstrom} resolution. The structure showed that the presence of Arg-118 poses a unique, possibly steric and/or electrostatic incompatibility that could impede E3 interactions with the wild-type hSBDb. Compared with the E3/E3BD structure, the hE3/hSBDb* structure has a smaller interfacial area. Solution NMR data corroborated the interactions of hE3 with Arg-118 and Asn-118 in wild-type hSBDb and mutant hSBDb*, respectively. The NMR results also showed that the interface between hSBDb and hE3 does not change significantly from hSBDb to hSBDb*. Taken together, our results represent a starting point for explaining the long standing enigma that the E2b core of the BCKDC binds E3 far more weakly relative to other {alpha}-ketoacid dehydrogenase complexes.

Abiotic and Biotic Degradation of Oxo-Biodegradable Plastic Bags by Pleurotus ostreatus

OpenAIRE

da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Bazzolli, Denise Mara Soares; Tótola, Marcos Rogério; Demuner, Antônio Jacinto; Kasuya, Maria Catarina Megumi

2014-01-01

In this study, we evaluated the growth of Pleurotus ostreatus PLO6 using oxo-biodegradable plastics as a carbon and energy source. Oxo-biodegradable polymers contain pro-oxidants that accelerate their physical and biological degradation. These polymers were developed to decrease the accumulation of plastic waste in landfills. To study the degradation of the plastic polymers, oxo-biodegradable plastic bags were exposed to sunlight for up to 120 days, and fragments of these bags were used as su...

Catalpic acid decreases abdominal fat deposition, improves glucose homeostasis and upregulates PPAR alpha expression in adipose tissue.

Science.gov (United States)

Hontecillas, Raquel; Diguardo, Maggie; Duran, Elisa; Orpi, Marcel; Bassaganya-Riera, Josep

2008-10-01

Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing trans-9, trans-11, cis-13 double bonds in an 18-carbon chain and it is found primarily in the seed oil of ornamental and medicinal trees and shrubs of the family Bignoniaceae. The objective of this study was to investigate whether CAT decreases obesity and ameliorates insulin sensitivity and glucose tolerance in mice fed high-fat diets. To test the efficacy of CAT in decreasing obesity and diabetes we used both a model of diet-induced obesity (DIO) and a genetic model of obesity (i.e., mice lacking the leptin receptor). Blood was collected on days 0, 7, 14, 21 and 28 for determining fasting glucose and insulin concentrations in plasma. In addition, a glucose tolerance test was administered on day 28. We found that dietary CAT (1g/100g) decreased fasting plasma glucose and insulin concentrations, ameliorated the glucose normalizing ability following glucose challenge and decreased abdominal white adipose tissue accumulation. In white adipose tissue (WAT), CAT upregulated peroxisome proliferator-activated receptor (PPAR) alpha and its responsive genes [i.e., stearoyl-coenzyme A desaturase (SCD1) and enoyl-coenzyme A hydratase (ECH)], increased concentrations of high-density lipoprotein (HDL) cholesterol and decreased plasma triglyceride (TG) levels. CAT decreased abdominal fat deposition, increased HDL cholesterol, decreased TG concentrations, decreased glucose and insulin homeostasis and modulated WAT gene expression in a manner reminiscent of the actions of the PPAR alpha-activating fibrate class of lipid-lowering drugs.

Synthesis of omega-hydroxy carboxylic acids and alpha,omega-dimethyl ketones using alpha,omega-diols as alkylating agents.

Science.gov (United States)

Iuchi, Yosuke; Hyotanishi, Megumi; Miller, Brittany E; Maeda, Kensaku; Obora, Yasushi; Ishii, Yasutaka

2010-03-05

Synthesis of omega-hydroxy carboxylic acids and alpha,omega-dimethyl diketones was successfully achieved by using alpha,omega-diols as alkylating agents under the influence of an iridium catalyst. For example, the alkylation of butyl cyanoacetate with 1,13-tridecanediol in the presence of [IrCl(cod)](2) or [IrCl(coe)(2)](2) gave rise to butyl 2-cyano-15-hydroxypentadecanoate in good yield which is easily converted to cyclopentadecanolide (CPDL). In addition, the alkylation of acetone with 1,10-decanediol in the presence of [IrCl(cod)](2) and KOH resulted in an important muscone precursor, 2,15-hexadecanedione (HDDO), in good yield.

Kinetic studies of acid inactivation of alpha-amylase from Aspergillus oryzae

DEFF Research Database (Denmark)

Carlsen, Morten; Nielsen, Jens Bredal; Villadsen, John

1996-01-01

The stability of alpha-amylase from Aspergillus oryzae has been studied at different pH. The enzyme is extremely stable at neutral pH (pH 5-8), whereas outside this pH-range a substantial loss of activity is observed. The acid-inactivation of alpha-amylase from A. oryzae was monitored on...... regains part of its activity, and the reactivation process also follows first-order kinetics. The irreversible loss of activity is found not to result from a protease contamination of the protein samples. A proposed model, where irreversibly inactivated a-amylase is formed both directly from the active...

[Overexpression of four fatty acid synthase genes elevated the efficiency of long-chain polyunsaturated fatty acids biosynthesis in mammalian cells].

Science.gov (United States)

Zhu, Guiming; Saleh, Abdulmomen Ali Mohammed; Bahwal, Said Ahmed; Wang, Kunfu; Wang, Mingfu; Wang, Didi; Ge, Tangdong; Sun, Jie

2014-09-01

Three long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), are the most biologically active polyunsaturated fatty acids in the body. They are important in developing and maintaining the brain function, and in preventing and treating many diseases such as cardiovascular disease, inflammation and cancer. Although mammals can biosynthesize these long-chain polyunsaturated fatty acids, the efficiency is very low and dietary intake is needed to meet the requirement. In this study, a multiple-genes expression vector carrying mammalian A6/A5 fatty acid desaturases and multiple-genes expression vector carrying mammalian Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases coding genes was used to transfect HEK293T cells, then the overexpression of the target genes was detected. GC-MS analysis shows that the biosynthesis efficiency and level of DHA, EPA and ARA were significantly increased in cells transfected with the multiple-genes expression vector. Particularly, DHA level in these cells was 2.5 times higher than in the control cells. This study indicates mammal possess a certain mechanism for suppression of high level of biosynthesis of long chain polyunsaturated fatty acids, and the overexpression of Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases broke this suppression mechanism so that the level of DHA, EPA and ARA was significantly increased. This study also provides a basis for potential applications of this gene construct in transgenic animal to produce high level of these long-chain polyunsaturated fatty acid.

Chemical reactivity of {alpha}-isosaccharinic acid in heterogeneous alkaline systems

Energy Technology Data Exchange (ETDEWEB)

Glaus, M. A.; Loon, L. R. Van

2009-05-15

Cellulose degradation under alkaline conditions is of relevance for the mobility of many radionuclides in the near-field of a cementitious repository for radioactive waste, because metal-binding degradation products may be formed. Among these, {alpha}- isosaccharinic acid ({alpha}-ISA) is the strongest complexant. The prediction of the equilibrium concentration of {alpha}-ISA in cement pore water is therefore an important step in the assessment of the influence of cellulose degradation products on the speciation of radionuclides in such environments. The present report focuses on possible chemical transformation reactions of {alpha}-ISA in heterogeneous alkaline model systems containing either Ca(OH){sub 2} or crushed hardened cement paste. The transformation reactions were monitored by measuring the concentration of {alpha}-ISA by high performance anion exchange chromatography and the formation of reaction products by high performance ion exclusion chromatography. The overall loss of organic species from solution was monitored by measuring the concentration of non-purgeable organic carbon. The reactions were examined in diluted and compacted suspensions, at either 25 {sup o}C or 90 {sup o}C, and under anaerobic atmospheres obtained by various methods. It was found that {alpha}-ISA was transformed under all conditions tested to some extent. Reaction products, such as glycolate, formate, lactate and acetate, all compounds with less complexing strength than {alpha}-ISA, were detected. The amount of reaction products identified by the chromatographic technique applied was {approx} 50 % of the amount of {alpha}-ISA reacted. Sorption of {alpha}-ISA to Ca(OH){sub 2} contributed only to a minor extent to the loss of {alpha}-ISA from the solution phase. As the most important conclusion of the present work it was demonstrated that the presence of oxidising agents had a distinctive influence on the turnover of {alpha}-ISA. Under aerobic conditions {alpha}-ISA was

Gas chromatography/mass spectrometry analysis of very long chain fatty acids, docosahexaenoic acid, phytanic acid and plasmalogen for the screening of peroxisomal disorders

NARCIS (Netherlands)

Takemoto, Yasuhiko; Suzuki, Yasuyuki; Horibe, Ryoko; Shimozawa, Nobuyuki; Wanders, Ronald J. A.; Kondo, Naomi

2003-01-01

Very long chain fatty acids (VLCFAs) and docosahexaenoic acid (DHA), phytanic acid, and plasmalogens are usually measured individually. A novel method for the screening of peroxisomal disorders, using gas chromatography/mass spectrometry (GC/MS), was developed. Saturated and unsaturated fatty acids,

N-terminal amino acid sequence of Bacillus licheniformis alpha-amylase: comparison with Bacillus amyloliquefaciens and Bacillus subtilis Enzymes.

OpenAIRE

Kuhn, H; Fietzek, P P; Lampen, J O

1982-01-01

The thermostable, liquefying alpha-amylase from Bacillus licheniformis was immunologically cross-reactive with the thermolabile, liquefying alpha-amylase from Bacillus amyloliquefaciens. Their N-terminal amino acid sequences showed extensive homology with each other, but not with the saccharifying alpha-amylases of Bacillus subtilis.

Salicylic acid binding of mitochondrial alpha-ketoglutarate dehydrogenase E2 affects mitochondrial oxidative phosphorylation and electron transport chain components and plays a role in basal defense against tobacco mosaic virus in tomato.

Science.gov (United States)

Liao, Yangwenke; Tian, Miaoying; Zhang, Huan; Li, Xin; Wang, Yu; Xia, Xiaojian; Zhou, Jie; Zhou, Yanhong; Yu, Jingquan; Shi, Kai; Klessig, Daniel F

2015-02-01

Salicylic acid (SA) plays a critical role in plant defense against pathogen invasion. SA-induced viral defense in plants is distinct from the pathways mediating bacterial and fungal defense and involves a specific pathway mediated by mitochondria; however, the underlying mechanisms remain largely unknown. The SA-binding activity of the recombinant tomato (Solanum lycopersicum) alpha-ketoglutarate dehydrogenase (Slα-kGDH) E2 subunit of the tricarboxylic acid (TCA) cycle was characterized. The biological role of this binding in plant defenses against tobacco mosaic virus (TMV) was further investigated via Slα-kGDH E2 silencing and transient overexpression in plants. Slα-kGDH E2 was found to bind SA in two independent assays. SA treatment, as well as Slα-kGDH E2 silencing, increased resistance to TMV. SA did not further enhance TMV defense in Slα-kGDH E2-silenced tomato plants but did reduce TMV susceptibility in Nicotiana benthamiana plants transiently overexpressing Slα-kGDH E2. Furthermore, Slα-kGDH E2-silencing-induced TMV resistance was fully blocked by bongkrekic acid application and alternative oxidase 1a silencing. These results indicated that binding by Slα-kGDH E2 of SA acts upstream of and affects the mitochondrial electron transport chain, which plays an important role in basal defense against TMV. The findings of this study help to elucidate the mechanisms of SA-induced viral defense. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

The Role of GPR84 in Medium-chain Saturated Fatty Acid Taste Transduction

OpenAIRE

Liu, Yan

2016-01-01

Previous research has shown the gustatory recognition of the long-chain unsaturated fatty acids. In this study, I showed for the first time that medium-chain saturated fatty acids (MCFAs) are effective taste stimuli at both the cellular and behavioral levels. The mechanisms of gustatory recognition of MCFAs in mice were also partially elucidated using pharmaceutical approaches. The inward currents induced by capric acid in mouse taste cells were significantly inhibited by the antagonists of G...

Synthesis of (E)-9-Oxo-2-decenoic acid (the queen substance of honeybee) from methyl 3-formylpropionate; 3-horumiruporopion san mechiru wo mochiita (E)-9-okiso-2-desen san (Mitsubachi joo busshitsu) no gosei

Energy Technology Data Exchange (ETDEWEB)

Tsukasa, H. [Toyotama Koryo Co. Ltd., Tokyo (Japan)

1997-05-20

The queen substance, (E)-9-oxo-2-decenoic acid (1) is a pheromone secreted by queen honeybee (Apis mellifera) and inhibits reproductive ability of worker bees. Several synthesese have been reported. It was synthesized starting from methyl-3-formylpropionate this time. Methyl 7,7-ethylenedioxy-4-oxooctanoate was prepared by radical addition reaction from (2) and 2-methyl-2-vinyl-1,3-dioxolane and reduced to an ethyelenedioxy carboxylic acid with hydrazine and KOH. This compound was converted to an alcohol by reduction with sodium bis(2-methoxyethoxy)aluminum hydride, followed by oxidation with pyridinium chlorochromate to an acetal aldehyde, which was condensed with malonic acid and (1) was obtained after the hydrolysis with hydrochloric acid. 7 refs., 1 tab.

Two-stage medium chain fatty acid (MCFA) production from municipal solid waste and ethanol

NARCIS (Netherlands)

Grootscholten, T.I.M.; Strik, D.P.B.T.B.; Steinbusch, K.J.J.; Buisman, C.J.N.; Hamelers, B.

2014-01-01

Chain elongation is an anaerobic fermentation that produces medium chain fatty acids (MCFAs) from volatile fatty acids and ethanol. These MCFAs can be used as biochemical building blocks for fuel production and other chemical processes. Producing MCFAs from the organic fraction of municipal solid

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats.

Science.gov (United States)

Nakano, Masako; Onodera, Aya; Saito, Emi; Tanabe, Miyako; Yajima, Kazue; Takahashi, Jiro; Nguyen, Van Chuyen

2008-08-01

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.

Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems.

Science.gov (United States)

Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

2009-06-26

Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-alpha in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-alpha and oleic acid treated cells was evaluated using flow cytometry. PPAR-gamma translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-alpha inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-alpha and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Oleic acid was found to

Branched-Chain Amino Acids.

Science.gov (United States)

Yamamoto, Keisuke; Tsuchisaka, Atsunari; Yukawa, Hideaki

Branched-chain amino acids (BCAAs), viz., L-isoleucine, L-leucine, and L-valine, are essential amino acids that cannot be synthesized in higher organisms and are important nutrition for humans as well as livestock. They are also valued as synthetic intermediates for pharmaceuticals. Therefore, the demand for BCAAs in the feed and pharmaceutical industries is increasing continuously. Traditional industrial fermentative production of BCAAs was performed using microorganisms isolated by random mutagenesis. A collection of these classical strains was also scientifically useful to clarify the details of the BCAA biosynthetic pathways, which are tightly regulated by feedback inhibition and transcriptional attenuation. Based on this understanding of the metabolism of BCAAs, it is now possible for us to pursue strains with higher BCAA productivity using rational design and advanced molecular biology techniques. Additionally, systems biology approaches using augmented omics information help us to optimize carbon flux toward BCAA production. Here, we describe the biosynthetic pathways of BCAAs and their regulation and then overview the microorganisms developed for BCAA production. Other chemicals, including isobutanol, i.e., a second-generation biofuel, can be synthesized by branching the BCAA biosynthetic pathways, which are also outlined.

Interactions among the branched-chain amino acids and their effects on methionine utilization in growing pigs: effects on plasma amino- and keto-acid concentrations and branched-chain keto-acid dehydrogenase activity.

Science.gov (United States)

Langer, S; Scislowski, P W; Brown, D S; Dewey, P; Fuller, M F

2000-01-01

The present experiment was designed to elucidate the mechanism of the methionine-sparing effect of excess branched-chain amino acids (BCAA) reported in the previous paper (Langer & Fuller, 2000). Twelve growing gilts (30-35 kg) were prepared with arterial catheters. After recovery, they received for 7 d a semipurified diet with a balanced amino acid pattern. On the 7th day blood samples were taken before (16 h postabsorptive) and after the morning meal (4 h postprandial). The animals were then divided into three groups and received for a further 7 d a methionine-limiting diet (80% of requirement) (1) without any amino acid excess; (2) with excess leucine (50% over requirement); or (3) with excesses of all three BCAA (leucine, isoleucine, valine, each 50% over the requirement). On the 7th day blood samples were taken as in the first period, after which the animals were killed and liver and muscle samples taken. Plasma amino acid and branched-chain keto acid (BCKA) concentrations in the blood and branched-chain keto-acid dehydrogenase (BCKDH; EC 1.2.4.4) activity in liver and muscle homogenates were determined. Compared with those on the balanced diet, pigs fed on methionine-limiting diets had significantly lower (P < 0.05) plasma methionine concentrations in the postprandial but not in the postabsorptive state. There was no effect of either leucine or a mixture of all three BCAA fed in excess on plasma methionine concentrations. Excess dietary leucine reduced (P < 0.05) the plasma concentrations of isoleucine and valine in both the postprandial and postabsorptive states. Plasma concentrations of the BCKA reflected the changes in the corresponding amino acids. Basal BCKDH activity in the liver and total BCKDH activity in the biceps femoris muscle were significantly (P < 0.05) increased by excesses of leucine or all BCAA.

The influence of aliphatic side chain of anacardic acid on molecular ...

African Journals Online (AJOL)

Interestingly, the presence of the aliphatic side chain in AnMcr resulted in more uniform imprinted beads as compared to particle agglomerates obtained from SaMcr in the presence of propranolol template. Therefore, the aliphatic side chain of anacardic acid improves both molecular recognition of imprinted polymers as ...

Omega-3 long-chain polyunsaturated fatty acids support aerial insectivore performance more than food quantity.

Science.gov (United States)

Twining, Cornelia W; Brenna, J Thomas; Lawrence, Peter; Shipley, J Ryan; Tollefson, Troy N; Winkler, David W

2016-09-27

Once-abundant aerial insectivores, such as the Tree Swallow (Tachycineta bicolor), have declined steadily in the past several decades, making it imperative to understand all aspects of their ecology. Aerial insectivores forage on a mixture of aquatic and terrestrial insects that differ in fatty acid composition, specifically long-chain omega-3 polyunsaturated fatty acid (LCPUFA) content. Aquatic insects contain high levels of both LCPUFA and their precursor omega-3 PUFA, alpha-linolenic acid (ALA), whereas terrestrial insects contain much lower levels of both. We manipulated both the quantity and quality of food for Tree Swallow chicks in a full factorial design. Diets were either high-LCPUFA or low in LCPUFA but high in ALA, allowing us to separate the effects of direct LCPUFA in diet from the ability of Tree Swallows to convert their precursor, ALA, into LCPUFA. We found that fatty acid composition was more important for Tree Swallow chick performance than food quantity. On high-LCPUFA diets, chicks grew faster, were in better condition, and had greater immunocompetence and lower basal metabolic rates compared with chicks on both low LCPUFA diets. Increasing the quantity of high-LCPUFA diets resulted in improvements to all metrics of performance while increasing the quantity of low-LCPUFA diets only resulted in greater immunocompetence and lower metabolic rates. Chicks preferentially retained LCPUFA in brain and muscle when both food quantity and LCPUFA were limited. Our work suggests that fatty acid composition is an important dimension of aerial insectivore nutritional ecology and reinforces the importance of high-quality aquatic habitat for these declining birds.

Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial

OpenAIRE

Dolder, Patrick C.; Liechti, Matthias E.; Rentsch, Katharina M.

2018-01-01

Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide...

4-Hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethylphenyl]-1,2-dihydroquinoline-3-carboxamide

Directory of Open Access Journals (Sweden)

Emmanuel S. Akinboye

2014-03-01

Full Text Available The title compound, C20H17F3N2O4, named tasquinimod, is a second-generation oral quinoline-3-carboxamide analogue, which is currently in phase III clinical trials for the treatment of metastatic prostate cancer. The quinoline unit is almost planar (r.m.s. deviation of fitted atoms = 0.0075 Å. The carboxamide side chain, substituted at position 3, is tilted by 88.07 (7° to the quinoline plane. Both the methyl and carbonyl groups of this carboxamide side chain are in a syn conformation. The 4-(trifluoromethylphenyl plane is inclined at 50.62 (17° to the plane of the carboxamide side chain, and at 87.14 (4° to the plane of the quinoline ring system. The 4-hydroxy H atom acts as a double proton donor in an intramolecular hydrogen bond to the 5-position methoxy O atom and in an intermolecular contact to the 2-oxo group, generating a chain along [010] in the crystal structure.

Structural analyses of polymorphic transitions of sn-1, 3-distearoyl-2-oleoylglycerol (SOS) and sn-1, 3-dioleoyl-2-stearoylglycerol (OSO): assessment on steric hindrance of unsaturated and saturated acyl chain interactions.

Science.gov (United States)

Yano, J; Sato, K; Kaneko, F; Small, D M; Kodali, D R

1999-01-01

Polymorphic transformations in two saturated-unsaturated mixed acid triacylglycerols, SOS (sn -1,3-distearoyl-2-oleoylglycerol) and OSO (sn -1,3-dioleoyl-2-stearoylglycerol), have been studied by FT-IR spectroscopy using deuterated specimens in which stearoyl chains are fully deuterated. A reversible phase transition between sub alpha and alpha and a series of irreversible transitions (alpha-->gamma-->beta'-->beta (beta2, beta1) for SOS and alpha-->beta'-->beta for OSO) were studied with an emphasis on the conformational ordering process of stearoyl and oleoyl chains. The alpha-->sub alpha reversible transition was due to the orientational change of stearoyl chains in the lateral directions from the hexagonal subcell to a perpendicularly packed one. As the first stage of the series of irreversible transitions from alpha to beta, the conformational ordering of saturated chains took place in the alpha-->gamma transition of SOS and in the alpha-->beta' transition of OSO; one stearoyl chain in SOS and OSO takes the all-trans conformation and the second stearoyl chain in SOS takes the bent conformation like those observed in the most stable beta-type. As the final stage, the ordering of unsaturated chains occurred in the beta'-->beta transition both for SOS and OSO. A conversion in the layered structure from bilayer to trilayer was also accompanied by the conformational ordering in the alpha-->gamma transition of SOS and in the beta'-->beta transition of OSO.

miR-451 deficiency is associated with altered endometrial fibrinogen alpha chain expression and reduced endometriotic implant establishment in an experimental mouse model.

Directory of Open Access Journals (Sweden)

Warren B Nothnick

Full Text Available Endometriosis is defined as the growth of endometrial glandular and stromal components in ectopic locations and affects as many as 10% of all women of reproductive age. Despite its high prevalence, the pathogenesis of endometriosis remains poorly understood. MicroRNAs, small non-coding RNAs that post-transcriptionally regulate gene expression, are mis-expressed in endometriosis but a functional role in the disease pathogenesis remains uncertain. To examine the role of microRNA-451 (miR-451 in the initial development of endometriosis, we utilized a novel mouse model in which eutopic endometrial fragments used to induce endometriosis were deficient for miR-451. After induction of the disease, we evaluated the impact of this deficiency on implant development and survival. Loss of miR-451 expression resulted in a lower number of ectopic lesions established in vivo. Analysis of differential protein profiles between miR-451 deficient and wild-type endometrial fragments revealed that fibrinogen alpha polypeptide isoform 2 precursor was approximately 2-fold higher in the miR-451 null donor endometrial tissue and this elevated expression of the protein was associated with altered expression of the parent fibrinogen alpha chain mRNA and protein. As this polypeptide contains RGD amino acid "cell adhesion" motifs which could impact early establishment of lesion development, we examined and confirmed using a cyclic RGD peptide antagonist, that endometrial cell adhesion and endometriosis establishment could be respectively inhibited both in vitro and in vivo. Collectively, these results suggest that the reduced miR-451 eutopic endometrial expression does not enhance initial establishment of these fragments when displaced into the peritoneal cavity, that loss of eutopic endometrial miR-451 expression is associated with altered expression of fibrinogen alpha chain mRNA and protein, and that RGD cyclic peptide antagonists inhibit establishment of endometriosis

cis-Stilbene and (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)benzene as mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: influence of the oxygen source and the counterion on the diastereoselectivity of the competitive concerted and radical-type oxygen transfer.

Science.gov (United States)

Adam, Waldemar; Roschmann, Konrad J; Saha-Möller, Chantu R; Seebach, Dieter

2002-05-08

cis-Stilbene (1) has been epoxidized by a set of diverse oxygen donors [OxD], catalyzed by the Mn(III)(salen)X complexes 3 (X = Cl, PF(6)), to afford a mixture of cis- and trans-epoxides 2. The cis/trans ratios range from 29:71 (extensive isomerization) to 92:8, which depends both on the oxygen source [OxD] and on the counterion X of the catalyst. When (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)-benzene (4) is used as substrate, a mechanistic probe which differentiates between radical and cationic intermediates, no cationic ring-opening products are found in this epoxidation reaction; thus, isomerized epoxide product arises from intermediary radicals. The dependence of the diastereoselectivity on the oxygen source is rationalized in terms of a bifurcation step in the catalytic cycle, in which concerted Lewis-acid-activated oxygen transfer competes with stepwise epoxidation by the established Mn(V)(oxo) species. The experimental counterion effect is attributed to the computationally assessed ligand-dependent reaction profiles and stereoselectivities of the singlet, triplet, and quintet spin states available to the manganese species.

Fatty acid biosynthesis VII. Substrate control of chain-length of products synthesised by rat liver fatty acid synthetase

DEFF Research Database (Denmark)

Hansen, Heinz Johs. Max; Carey, E.M.; Dils, R.

1970-01-01

- 1. Gas-liquid and paper chromatography have been used to determine the chain-lengths of fatty acids synthesised by purified rat liver fatty acid synthetase from [1-14C]acetyl-CoA, [1,3-14C2]malonyl-CoA and from [1-14C]acetyl-CoA plus partially purified rat liver acetyl-CoA carboxylase. - 2....... A wide range (C4:0–C18:0) of fatty acids was synthesised and the proportions were modified by substrate concentrations in the same manner as for purified rabbit mammary gland fatty acid synthetase. - 3. The relative amount of radioactivity incorporated from added acetyl-CoA and malonyl-CoA depended...... of long-chain fatty acids was synthesised from carboxylated acetyl-CoA than from added malonyl-CoA. - 5. It is suggested that acetyl-CoA carboxylase may carboxylate acetate bound to fatty acid synthetase....

General synthesis of C-glycosyl amino acids via proline-catalyzed direct electrophilic alpha-amination of C-glycosylalkyl aldehydes.

Science.gov (United States)

Nuzzi, Andrea; Massi, Alessandro; Dondoni, Alessandro

2008-10-16

Non-natural axially and equatorially linked C-glycosyl alpha-amino acids (glycines, alanines, and CH2-serine isosteres) with either S or R alpha-configuration were prepared by D- and L-proline-catalyzed (de >95%) alpha-amination of C-glycosylalkyl aldehydes using dibenzyl azodicarboxylate as the electrophilic reagent.

A practical synthesis of long-chain iso-fatty acids (iso-C12–C19 and related natural products

Directory of Open Access Journals (Sweden)

Mark B. Richardson

2013-09-01

Full Text Available A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12–C19 was developed commencing with methyl undec-10-enoate (methyl undecylenate (for iso-C12–C14 or the C15 and C16 lactones pentadecanolide (for iso-C15–C17 and hexadecanolide (for iso-C18–C19. Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13–C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S-2,15-dimethylpalmitic acid, (S-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

Measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-guanosine in cerebrospinal fluid by ultra performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Weimann, Allan; Simonsen, Anja Hviid; Poulsen, Henrik E

2018-01-15

Increased levels of nucleosides modified by oxidation in human cerebrospinal fluid (CSF) have several times been reported in Alzheimer patients and patients suffering from Parkinson's disease. The focus has especially been on nucleosides containing the 8-hydroxylation of guanine. Only few reports on quantification of the ribonucleoside 8-oxo-7,8-dihydro-guanosine (8oxoGuo) in CSF have been published, whereas more have been published on the quantification of the deoxy-ribonucleoside 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodGuo). The reports on the quantification of 8oxodGuo concentrations in CSF report absolute concentrations varying by a factor >10 5 in healthy humans. This could indicate that there is a serious specificity problem in some of the methods. In this paper an isotope-dilution UPLC-MS/MS method with high specificity and sensitivity for the quantification of 8oxoGuo and 8oxodGuo in CSF is presented. LLOQ for the two analytes is determined to 4pM and 2pM, respectively. The calibration curves has been tested to be linear in the range from 4 to 3,000pM for 8oxoGuo and between 2 and 3,000pM for 8oxodGuo. Using a weighting factor of 1/x the correlation coefficient "r" for both analytes is >0.999. Copyright © 2017 Elsevier B.V. All rights reserved.

Formation of nitridotechnetium(VI) μ-oxo dimer complexes with EDTA and EDDA

International Nuclear Information System (INIS)

Takayama, T.; Kani, Y.; Sekine, T.; Kudo, H.; Yoshihara, K.

1995-01-01

Reactions of [ 99 TcNCl 4 ] - with ethylenediaminetetraacetic acid 4 (ETDA) and ethylenediamine-N,N'-diacetic acid (EDDA) in a mixture of water and acetone gave Tc VI N-EDTA and Tc VI N-EDTA complexes. The infrared spectra of both reaction products showed the existence of the Tc≡N and C=O groups. The elemental analysis indicated the 1:1 TcN-ligand ratio in the EDTA and EDDA complexes. Electrophoresis showed that the Tc VI -EDTA complex was an anionic species in a perchlorate solution. For the Tc VI N-EDDA complex, neutral and anionic species were formed, depending on the pH of the solution. Formation of the μ-oxo dimer complexes was suggested from the UV-Vis absorption spectra. (author) 11 refs.; 4 figs.; 1 tab

12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

Energy Technology Data Exchange (ETDEWEB)

Taki-Nakano, Nozomi [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Kotera, Jun [Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Ohta, Hiroyuki, E-mail: ohta.h.ab@m.titech.ac.jp [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan)

2016-05-13

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

International Nuclear Information System (INIS)

Taki-Nakano, Nozomi; Kotera, Jun; Ohta, Hiroyuki

2016-01-01

Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

Science.gov (United States)

Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

2009-01-01

Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

Nucleophilic Substitution and Redox Reactions with alpha-Chloro beta-Oxo Sulfenyl Chlorides

DEFF Research Database (Denmark)

El-Essawy, Farag A.G.; Yassin, Salah M.; El-Sakka, Ibrahim A.

1998-01-01

Alpha-Chloro sulfenyl chlorides such as 1 and 4 could not be reduced to the corresponding disulfides. Under reducing conditions they are instead dechlorinated to the corresponding thiocarbonyl compounds. Starting from the chroman-4-one derivatives 1 a number of 1,3,4-oxadithiins 3 have been prepa...

Oxidative stability of dark chicken meat through frozen storage: influence of dietary fat and alpha-tocopherol and ascorbic acid supplementation.

Science.gov (United States)

Grau, A; Guardiola, F; Grimpa, S; Barroeta, A C; Codony, R

2001-11-01

We used factorial design to ascertain the influence of dietary fat source (linseed, sunflower and oxidized sunflower oils, and beef tallow) and the dietary supplementation with alpha-tocopheryl acetate (alpha-TA) (225 mg/kg of feed) and ascorbic acid (AA) (110 mg/kg) on dark chicken meat oxidation (lipid hydroperoxide and TBA values and cholesterol oxidation product content). alpha-TA greatly protected ground and vacuum-packaged raw or cooked meat from fatty acid and cholesterol oxidation after 0, 3.5, or 7 mo of storage at -20 C. In contrast, AA provided no protection, and no synergism between alpha-TA and AA was observed. Polyunsaturated fatty acid-enriched diets (those containing linseed, sunflower, or oxidized sunflower oils) increased meat susceptibility to oxidation. Cooking always involved more oxidation, especially in samples from linseed oil diets. The values of all the oxidative parameters showed a highly significant negative correlation with the alpha-tocopherol content of meat.

Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, an α-hydroxy acid from rooibos (Aspalathus linearis) with hypoglycemic activity

DEFF Research Database (Denmark)

Muller, C.J.F.; Joubert, Elizabeth; Pheiffer, Carmen

2013-01-01

Scope: The rare enolic phenylpyruvic acid glucoside, Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG) is one of the major constituents of fermented rooibos infusions. 3-Phenylpyruvic acid (2-oxo-3-phenylpropanoic acid) (PPA), without the sugar moiety and with a keto instead of enolic arr...

[Cholesterol metabolism and lipid peroxidation processes in hypodynamia. Effect of using ascorbic acid and alpha-tocopherol].

Science.gov (United States)

Elikov, A V; Tsapok, P I

2010-01-01

Study status of cholesterol metabolism, processes of lipid peroxidation and antioxidant protection in blood plasma, erythrocytes and homogenates of the, heart, liver, muscle femors of rats attached to movement active. Establishment effects application of ascorbic acid and alpha-tocopherol. Ascorbic acid and alpha-tocopherol were infused daily. The daily dosage was 2 and 1 mg respectively. Characteristic shift changes of cholesterol metabolism in conditions of limited muscular activity were revealed. It was shown that vitamin antioxidants play a role in correction of metabolic disorders in case of immobile distress syndrome.

Alkylation of amide linkages and cleavage of the C chain in the enzyme-activated-substrate inhibition of alpha-chymotrypsin with N-nitrosamides

International Nuclear Information System (INIS)

Donadio, S.; Perks, H.M.; Tsuchiya, K.; White, E.H.

1985-01-01

Active-site-directed N-nitrosamides inhibit alpha-chymotrypsin through an enzyme-activated-substrate mechanism. In this work, the activation results in the release--in the active site--of benzyl carbonium ions, which alkylate and inhibit the enzyme. The final ratio of benzyl groups to enzyme molecules is 1.0, but the alkyl groups are scattered over a number of sites. Reduction and alkylation of the inhibited enzyme generate peptides insoluble in most media. Guanidine hydrochloride at 6 M proved a good solvent, and its use as an eluant on G-75 Sephadex permitted separation of the peptides. In the case of 14 C-labeled enzyme, such an approach has shown that all of the alkylation occurs on the C chain of the enzyme, the chain of which the active site is constructed. Chemical modification of the peptides with ethylenediamine and N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide rendered them soluble in dilute acid, permitting high-performance liquid chromatographic separation. Model studies have shown that the benzyl carbonium ions are highly reactive, alkylating amide linkages at both oxygen and nitrogen. Chromatography of this mixture and also 13 C NMR spectroscopy of the intact inhibited enzyme have shown that three major N-alkylations have occurred. Tryptic digestion of the C chain of chymotrypsin, which contains all of the alkylation sites, provides evidence that the stable N sites are principally located between residue 216 and residue 230

Amino acid metabolism during exercise in trained rats: the potential role of carnitine in the metabolic fate of branched-chain amino acids.

Science.gov (United States)

Ji, L L; Miller, R H; Nagle, F J; Lardy, H A; Stratman, F W

1987-08-01

The influence of endurance training and an acute bout of exercise on plasma concentrations of free amino acids and the intermediates of branched-chain amino acid (BCAA) metabolism were investigated in the rat. Training did not affect the plasma amino acid levels in the resting state. Plasma concentrations of alanine (Ala), aspartic acid (Asp), asparagine (Asn), arginine (Arg), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), and valine (Val) were significantly lower, whereas glutamate (Glu), glycine (Gly), ornithine (Orn), tryptophan (Trp), tyrosine (Tyr), creatinine, urea, and ammonia levels were unchanged, after one hour of treadmill running in the trained rats. Plasma concentration of glutamine (Glu), the branched-chain keto acids (BCKA) and short-chain acyl carnitines were elevated with exercise. Ratios of plasma BCAA/BCKA were dramatically lowered by exercise in the trained rats. A decrease in plasma-free carnitine levels was also observed. These data suggest that amino acid metabolism is enhanced by exercise even in the trained state. BCAA may only be partially metabolized within muscle and some of their carbon skeletons are released into the circulation in forms of BCKA and short-chain acyl carnitines.

Activity of L-alpha-amino acids at the promiscuous goldfish odorant receptor 5.24

DEFF Research Database (Denmark)

Christiansen, Bolette; Wellendorph, Petrine; Bräuner-Osborne, Hans

2006-01-01

The goldfish odorant receptor 5.24 is a member of family C of G protein-coupled receptors and is closely related to the human receptor GPRC6A. Receptor 5.24 has previously been shown to have binding affinity for L-alpha-amino acids, especially the basic amino acids arginine and lysine. Here we...

Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA: results from the alpha omega trial.

Directory of Open Access Journals (Sweden)

Ingeborg A Brouwer

Full Text Available Alpha linolenic acid (ALA is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA, a biomarker for prostate cancer.The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452 was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA and docosahexanoic acid (DHA on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60-80 years with an initial PSA concentration 4 ng/mL.Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815 and by 0.52 ng/mL on ALA (n = 807, a difference of 0.10 (95% confidence interval: -0.02 to 0.22 ng/mL (P = 0·12. The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58.An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

Synthesis and antimicrobial evaluation of new 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinones.

Science.gov (United States)

Güzeldemirci, Nuray Ulusoy; Ilhan, Eser; Küçükbasmaci, Omer; Satana, Dilek

2010-01-01

New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

Alfalfa contains substantial 9-hydroperoxide lyase activity and a 3Z:2E-enal isomerase

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Noordermeer, M.A.; Veldink, G.A.

1999-01-01

Fatty acid hydroperoxides formed by lipoxygenase can be cleaved by hydroperoxide lyase resulting in the formation of short-chain aldehydes and omega-oxo acids. Plant hydroperoxide lyases use 13- or 9-hydroperoxy linoleic and linolenic acid as substrates. Alfalfa (Medicago sativa L.) has been

Simultaneous improvement in production of microalgal biodiesel and high-value alpha-linolenic acid by a single regulator acetylcholine.

Science.gov (United States)

Parsaeimehr, Ali; Sun, Zhilan; Dou, Xiao; Chen, Yi-Feng

2015-01-01

Photoautotrophic microalgae are a promising avenue for sustained biodiesel production, but are compromised by low yields of biomass and lipids at present. We are developing a chemical approach to improve microalgal accumulation of feedstock lipids as well as high-value alpha-linolenic acid which in turn might provide a driving force for biodiesel production. We demonstrate the effectiveness of the small bioactive molecule "acetylcholine" on accumulation of biomass, total lipids, and alpha-linolenic acid in Chlorella sorokiniana. The effectiveness exists in different species of Chlorella. Moreover, the precursor and analogs of acetylcholine display increased effectiveness at higher applied doses, with maximal increases by 126, 80, and 60% over controls for biomass, total lipids, and alpha-linolenic acid, respectively. Production of calculated biodiesel was also improved by the precursor and analogs of acetylcholine. The biodiesel quality affected by changes in microalgal fatty acid composition was addressed. The chemical approach described here could improve the lipid yield and biodiesel production of photoautotrophic microalgae if combined with current genetic approaches.

Can long chain n-3 fatty acids from feed be converted into very long chain n-3 fatty acids in fillets from farmed rainbow trout (Oncorhynchus mykiss)?

Science.gov (United States)

Lušnic Polak, M.; Demšar, L.; Luzar, U.; Polak, T.

2017-09-01

The link between the basic chemical and fatty acid composition of trout feed on one hand and trout (Oncorhynchus mykiss) meat (fillet) was investigated.. The content of 52 fatty acids from feed and trout meat lipids was determined by in-situ transesterification and capillary column gas-liquid chromatography. On average, 100 g of trout feed contained 7.4 g of moisture, 47.7 g of proteins, 6.09 g of ash, 21.4 g of fat, and as for fatty acid composition, 47.8 wt. % were monounsaturated, 34.0 wt. % were polyunsaturated and 18.1 wt. % were saturated fatty acids, with the PS ratio 1.88, n-6/n-3 ratio 1.74, 0.80 wt. % of trans and 3.28 wt. % of very long chain n-3 fatty acids. On average, 100 g of trout meat contained 76.1 g of moisture, 21.4 g of proteins, 1.34 g of ash, 2.52 g of fat, and in the fatty acid composition 42.1 wt. % were monounsaturated, 38.2 wt. % were polyunsaturated and 18.9 wt. % were saturated fatty acids, with the PS ratio 2.02, n-6/n-3 ratio 0.98, 0.95 wt. % of trans and 13.25 wt. % of very long chain n-3 fatty acids.

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

Science.gov (United States)

Vivar, Juan C.; Knight, Megan S.; Pointer, Mildred A.; Gwathmey, Judith K.; Ghosh, Sujoy

2014-01-01

The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of

Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes.

Directory of Open Access Journals (Sweden)

Abderrazak Kitsy

Full Text Available The essential branched-chain amino acids (BCAA, leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2 and branched-chain alpha keto acid dehydrogenase (Bckdha was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4 compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our

[Application of the polymerase chain reaction (PCR) in the diagnosis of Hb S-beta(+)-thalassemia].

Science.gov (United States)

Harano, K; Harano, T; Kushida, Y; Ueda, S

1991-08-01

Isoelectric focusing of the hemolysate prepared from a two-year-old American black boy with microcytic hypochromia showed the presence of a high percentage (63.3%) of such Hb variant as Hb S, while the levels of Hb A, Hb F and Hb A2 were 20.0%, 12.7%, and 4.0%, respectively. The ratio of the non-alpha-chain to the alpha-chain of the biosynthesized globin chains was 0.49. The variant was identified as Hb S by amino acid analysis of the abnormal peptide (beta T-1) and digestion of DNA amplified by the polymerase chain reaction with enzyme Eco 81 I. This was further confirmed by DNA sequencing. DNA sequencing of a beta-gene without the beta s-mutation revealed a nucleotide change of T to C in the polyadenylation signal sequence AATAAA 3' to the beta-gene, resulting in beta(+)-thalassemia. These results are consistent with the existence of a beta s-gene and a beta(+)-thalassemia gene in trans.

Minor amounts of plasma medium-chain fatty acids and no improved time trial performance after consuming lipids

DEFF Research Database (Denmark)

Vistisen, Bodil; Nybo, L.; Xu, Xuebing

2003-01-01

after consumption of specific structured triacylglycerol, consisting of a mixture of medium-chain fatty acids and long-chain fatty acids, to prevent the adverse effects observed by MCT (pure medium-chain fatty acids) regarding gastrointestinal distress. Seven well-trained subjects cycled 3 h at 55......% of maximum 02 uptake during which they ingested CHO or CHO plus specific structured triacylglycerols. Immediately after the constant-load cycling, the subjects performed a time trial of similar to50-min duration. Breath and blood samples were obtained regularly during the experiment. Fatty acid composition...... of plasma triacylglycerols, fatty acids, and phospholipids was determined. Performance was similar after administration of CHO plus specific structured triacylglycerol [medium-, long-, and medium-chain fatty acid (MLM)] compared with CHO (50.0 +/- 1.8 and 50.8 +/- 3.6 min, respectively). No plasma 8...

Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial

Science.gov (United States)

Palacios-Sánchez, Begoña; Cerero-Lapiedra, Rocío; Llamas-Martínez, Silvia; Esparza-Gómez, Germán

2015-01-01

Background A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease. Material and Methods 60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months. Results 64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms. Conclusions Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment. Key words: Burning mouth syndrome, neuropathy, alpha lipoic acid. PMID:26034927

Butyrate and other short-chain fatty acids increase the rate of lipolysis in 3T3-L1 adipocytes

Directory of Open Access Journals (Sweden)

John M. Rumberger

2014-10-01

Full Text Available We determined the effect of butyrate and other short-chain fatty acids (SCFA on rates of lipolysis in 3T3-L1 adipocytes. Prolonged treatment with butyrate (5 mM increased the rate of lipolysis approximately 2–3-fold. Aminobutyric acid and acetate had little or no effect on lipolysis, however propionate stimulated lipolysis, suggesting that butyrate and propionate act through their shared activity as histone deacetylase (HDAC inhibitors. Consistent with this, the HDAC inhibitor trichostatin A (1 µM also stimulated lipolysis to a similar extent as did butyrate. Western blot data suggested that neither mitogen-activated protein kinase (MAPK activation nor perilipin down-regulation are necessary for SCFA-induced lipolysis. Stimulation of lipolysis with butyrate and trichostatin A was glucose-dependent. Changes in AMP-activated protein kinase (AMPK phosphorylation mediated by glucose were independent of changes in rates of lipolysis. The glycolytic inhibitor iodoacetate prevented both butyrate- and tumor necrosis factor-alpha-(TNF-α mediated increases in rates of lipolysis indicating glucose metabolism is required. However, unlike TNF-α– , butyrate-stimulated lipolysis was not associated with increased lactate release or inhibited by activation of pyruvate dehydrogenase (PDH with dichloroacetate. These data demonstrate an important relationship between lipolytic activity and reported HDAC inhibitory activity of butyrate, other short-chain fatty acids and trichostatin A. Given that HDAC inhibitors are presently being evaluated for the treatment of diabetes and other disorders, more work will be essential to determine if these effects on lipolysis are due to inhibition of HDAC.

Orphan drugs in development for long-chain fatty acid oxidation disorders: challenges and progress

Directory of Open Access Journals (Sweden)

Sun A

2015-04-01

Full Text Available Angela Sun, J Lawrence Merritt II Department of Pediatrics, University of Washington, Seattle, WA, USA Abstract: Fatty acid oxidation disorders are inborn errors of metabolism resulting in failure of ß-oxidation within or transport of fatty acids into the mitochondria. The long-chain fatty acid oxidation disorders are characterized by variable presentations ranging from newborn cardiomyopathy, to infantile hypoketotic hypoglycemia resulting from liver involvement, to skeletal myopathy often resulting in rhabdomyolysis in adolescents and adults. Treatments for these long-chain fatty acid oxidation disorders have typically focused upon avoidance of fasting with dietary fat restriction and medium-chain triglyceride supplementation. These treatments have resulted in only a partial response with improvements in hypoglycemia, reduction in frequency of rhabdomyolysis, and improvement in cardiomyopathy with early therapy, but significant risk remains. Recent advances in therapies for long-chain fatty acid oxidation disorders are reviewed in this article. These include sodium D,L-3-hydroxybutyrate, triheptanoin, gene therapy, and bezafibrates. Sodium D,L-3-hydroxybutyrate has shown clinical effect, with improvements in muscle tone, neurological abnormalities, and some cases of cardiomyopathy and leukodystrophy. Triheptanoin has been used as an alternative medium-chain triglyceride in a number of fatty acid oxidation disorders and has shown promising findings in the treatment of cardiomyopathy and hypoglycemia. However, it does not significantly reduce episodes of rhabdomyolysis. Gene therapy has been shown to improve acylcarnitine levels in very-long-chain acyl-coenzyme A dehydrogenase deficiency mouse models, with preservation of glucose levels. Bezafibrates have shown improvements in acylcarnitine concentrations in fibroblast studies, but clinical observations have not demonstrated consistent effects. Together, these treatments have shown some

Alpha-eleostearic acid (9Z11E13E-18:3) is quickly converted to conjugated linoleic acid (9Z11E-18:2) in rats.

Science.gov (United States)

Tsuzuki, Tsuyoshi; Tokuyama, Yoshiko; Igarashi, Miki; Nakagawa, Kiyotaka; Ohsaki, Yusuke; Komai, Michio; Miyazawa, Teruo

2004-10-01

We previously showed that alpha-eleostearic acid (alpha-ESA; 9Z11E13E-18:3) is converted to conjugated linoleic acid (CLA; 9,11-18:2) in the liver and plasma of rats that were given diets including 1% alpha-ESA for 4 wk. In this study, we investigated this phenomenon in detail. First, the chemical structure of CLA produced by alpha-ESA administration was determined. After alpha-ESA was orally administered to rats, CLA in rat liver was isolated by HPLC. The positional and geometric isomerism was determined using GC-EI/MS and (13)C-NMR, respectively, and the CLA generated in rats after alpha-ESA feeding was confirmed to be 9Z11E-CLA. Next, the concentrations of alpha-ESA and CLA were determined 0, 3, 6, and 24 h after oral administration of alpha-ESA to rats. Moreover, we also investigated whether enteric bacteria are involved in the conversion of alpha-ESA to CLA using germ-free rats. alpha-ESA was orally administered to germ-free and normal rats and alpha-ESA and CLA were detected in the organs of both groups. In addition, to confirm that this reaction was enzyme-mediated, alpha-ESA was reacted with tissue homogenates (liver, kidney, and small intestine mucous) and coenzymes (NADH, NAD(+), NADPH, and NADP(+)), and the enzyme activities were estimated from the amount of CLA produced. CLA was detected when alpha-ESA was reacted with liver, kidney, and small intestine mucous homogenates and a coenzyme (NADPH). These results indicated that alpha-ESA is converted to 9Z11E-CLA in rats by a Delta13-saturation reaction carried out by an NADPH-dependent enzyme.

Branched-chain amino acids for people with hepatic encephalopathy

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

2015-01-01

-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. SEARCH METHODS: We identified trials through...

Branched-chain amino acids for people with hepatic encephalopathy

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo

2017-01-01

-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. Objectives: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. Search methods: We identified trials through...

LC-mS analysis of human urine specimens for 2-oxo-3-hydroxy LSD: method validation for potential interferants and stability study of 2-oxo-3-hydroxy LSD under various storage conditions.

Science.gov (United States)

Klette, Kevin L; Horn, Carl K; Stout, Peter R; Anderson, Cynthia J

2002-01-01

2-Oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), a major LSD metabolite, has previously been demonstrated to be a superior marker for identifying LSD use compared with the parent drug, LSD. Specifically, O-H-LSD analyzed using liquid chromatography-mass spectrometry has been reported to be present in urine at concentrations 16 to 43 times greater than LSD. To further support forensic application of this procedure, the specificity of the assay was assessed using compounds that have structural and chemical properties similar to O-H-LSD, common over-the-counter products, prescription drugs and some of their metabolites, and other drugs of abuse. Of the wide range of compounds studied, none were found to interfere with the detection of O-H-LSD or the internal standard 2-oxo-3-hydroxy lysergic acid methyl propylamide. The stability of O-H-LSD was investigated from 0 to 9 days at various temperatures, pH conditions, and exposures to fluorescent light. Additionally, the effect of long-term frozen storage and pH was investigated from 0 to 60 days. There was no significant loss of O-H-LSD under both refrigerated and frozen conditions within the normal human physiological pH range of urine (4.6-8.4). However, significant loss of O-H-LSD was observed in samples prepared at pH 4.6-8.4 and stored at room temperature or higher (24-50 degrees C).

The properties of the single chicken MHC classical class II alpha chain (B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

DEFF Research Database (Denmark)

Salomonsen, Jan; Marston, Denise; Avila, David

2003-01-01

for the cloning and sequencing of the cDNA. We found only one class II alpha chain transcript, which bears the major features of a classical class II alpha sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most...... the mammalian DR and E isotypes in three properties: the presence of the critical peptide-binding residues, the low level of polymorphism and sequence diversity, and the recombinational separation from the class II beta chain genes. These results indicate that the sequence features of this lineage are both......In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) alpha chain from outbred chickens as the basis...

Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients.

Science.gov (United States)

Asemi, Zatollah; Soleimani, Alireza; Shakeri, Hossein; Mazroii, Navid; Esmaillzadeh, Ahmad

2016-11-01

The current study was carried out to assess the effects of omega-3 fatty acid and alpha-tocopherol co-supplementation on malnutrition-inflammation score (MIS), biomarkers of inflammation and oxidative stress in chronic hemodialysis (HD) patients. In a randomized double-blind placebo-controlled clinical trial, 120 patients with chronic HD were included. Patients were randomly allocated into four groups to receive: (1) 1250 mg/day omega-3 fatty acid containing 600 mg EPA and 300 mg DHA + alpha-tocopherol placebo (n = 30); (2) 400 IU/day alpha-tocopherol + omega-3 fatty acids placebo (n = 30); (3) 1250 mg omega-3 fatty acids/day + 400 IU/day alpha-tocopherol (n = 30); and (4) omega-3 fatty acids placebo + alpha-tocopherol placebo (n = 30) for 12 weeks. After 12 weeks of intervention, all three groups of alpha-tocopherol only, individual omega-3 fatty acids, and combined omega-3 fatty acids and alpha-tocopherol experienced a significant improvements in MIS compared with the placebo group; however, improvements were much greater in the individual omega-3 fats (-1.4 ± 1.4) and combined omega-3 fats and alpha-tocopherol (-1.1 ± 2.3) groups compared with alpha-tocopherol group alone (-0.5 ± 1.7, P = 0.004). Furthermore, both individual and combined intervention with omega-3 fats and alpha-tocopherol led to a significant increase in plasma nitric oxide (NO) (combined group: +17.6 ± 29.3; alpha-tocopherol: +43.1 ± 36.3; omega-3 fats: +31.0 ± 40.0; and placebo: -0.5 ± 18.5 µmol/L, respectively, P acids and alpha-tocopherol co-supplementation for 12 weeks among HD patients improved MIS, plasma NO and TAC levels. Future studies with longer duration of the intervention are needed to confirm the validity of our findings. CLINICAL REGISTRATION: www.irct.ir as IRCT201410245623N28.

Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial.

Science.gov (United States)

Dolder, Patrick C; Liechti, Matthias E; Rentsch, Katharina M

2018-02-01

Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide (LAE), lysergic acid ethyl-2-hydroxyethylamide (LEO), 2-oxo-LSD, trioxylated-LSD, and 13/14-hydroxy-LSD, should be identified. Separation of LSD and its metabolites was achieved on a reversed phase chromatography column after turbulent-flow online extraction. For the identification and quantification, a triple-stage quadrupole LC-MS/MS instrument was used. The validation data showed slight matrix effects for LSD, iso-LSD, O-H-LSD, or nor-LSD. Mean intraday and interday accuracy and precision were 105%/4.81% and 105%/4.35% for LSD, 98.7%/5.75% and 99.4%/7.21% for iso-LSD, 106%/4.54% and 99.4%/7.21% for O-H-LSD, and 107%/5.82% and 102%/5.88% for nor-LSD, respectively. The limit of quantification was 0.05 ng/mL for LSD, iso-LSD, and nor-LSD and 0.1 ng/mL for O-H-LSD. The limit of detection was 0.01 ng/mL for all compounds. The method described herein was accurate, precise, and the calibration range within the range of expected plasma concentrations. LSD was quantified in the plasma samples of the 24 subjects of the clinical trial, whereas iso-LSD, O-H-LSD, nor-LSD, LAE, LEO, 13/14-hydroxy-LSD, and 2-oxo-LSD could only sporadically be detected but were too low for quantification. © 2017 Wiley Periodicals, Inc.

WAD, a program to calculate the heat produced by alpha decay

International Nuclear Information System (INIS)

Jarvis, R.G.; Bretzlaff, C.I.

1982-09-01

The FORTRAN program WAD (Watts from Alpha Decay) deals with the alpha and beta decay chains to be encountered in advanced fuel cycles for CANDU reactors. The data library covers all necessary alpha-emitting and beta-emitting nuclides and the program calculates the heat produced by alpha decay. Any permissible chain can be constructed very simply

Pregnancy duration and the ratio of long-chain n-3 fatty acids to arachidonic acid in erythrocytes from Faroese women

DEFF Research Database (Denmark)

Olsen, S.F.; Hansen, Harald S.; Jensen, B.

1989-01-01

of long-chain n-3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient......Dietary long-chain n-3 fatty acids (FA) may prolong gestation by inhibiting formation of prostaglandins from arachidonic acid. FA were quantified in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipids (TL) of red cells sampled during pregnancy from 29 Faroese women. The ratio...

Fatty acid profile and composition of milk protein fraction in dairy cows fed long-chain unsaturated fatty acids during the transition period

Directory of Open Access Journals (Sweden)

Francisco Palma Rennó

2013-11-01

Full Text Available The objective of this study was to evaluate the utilization of different sources of unsaturated long-chain fatty acids in diets for dairy cows during the transition period and early lactation on the milk fatty acid profile and composition of the protein fraction. Thirty-six Holstein cows were divided into three groups, fed the following diets: control (C; soybean oil (SO; and calcium salts of long-chain unsaturated fatty acids (CS. The milk samples utilized for analysis were obtained weekly from parturition to twelve weeks of lactation; each one of the samples originated from two daily milkings. Milk composition and total nitrogen, non-protein nitrogen and non-casein nitrogen levels were analyzed. The cows receiving the diet with calcium salts had lower concentrations of non-protein nitrogen (%CP in milk compared with the animals fed the diet with soybean oil. There was a decrease in concentration of medium-chain fatty acids C12-C16, and a concomitant increase in concentrations of long-chain fatty acids >C18 in milk fat for the animals fed the diets CS and SO when compared with diet C. Soybean oil and CS diets increased milk-fat concentrations of the acids C18: 1 trans-11, C18: 2 cis-9, trans-11 and C18: 2 trans-10 cis-12 in relation to diet C. The utilization of sources of long-chain fatty acids in the diet of dairy cows increases the biological value of milk in early lactation due to higher concentrations of specific fatty acids such as CLA C18: 2cis-9, trans-11.

Effects of medium-chain fatty acids and oleic acid on blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities

DEFF Research Database (Denmark)

Tholstrup, T.; Ehnholm, C.; Jauhiainen, M.

2004-01-01

Background: Dietary medium-chain fatty acids (MCFAs) are of nutritional interest because they are more easily absorbed from dietary medium-chain triacylglycerols (MCTs) than are long-chain fatty acids from, for example, vegetable oils. It has generally been claimed that MCFAs do not increase plasma...... cholesterol, although this claim is poorly documented. Objective: We compared the effects of a diet rich in either MCFAs or oleic acid on fasting blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities in healthy men. Design: In a study with a double-blind, randomized, crossover...... plasma total triacylglycerol (P = 0.0361), and higher plasma glucose (P = 0.033). Plasma HDL-cholesterol and insulin concentrations and activities of cholesterol ester transfer protein and phospholipid transfer protein did not differ significantly between the diets. Conclusions: Compared with fat high...

“CLEAR BRANDY” PRODUCTION USING ALPHA ACID EXTRACT FROM HOPS IN THE BIOCIDAL CONTROL OF THE FERMENTATION PROCESS

Directory of Open Access Journals (Sweden)

Tassiana Amélia de Oliveira e Silva

2016-01-01

Full Text Available The major problem in the production of “clear brandy” is the contamination of the must by bacteria of the species Lactobacillus. To overcome this problem, this work intends to evaluate the usage of the alpha acids from hop extract (Humulus lupulus as antibacterial agent during brandy production. In addition, the maximum cell recycling was evaluated during the clear brandy production. Preliminary experiments using the Sabourand synthetic medium added with 40 ppm of the alpha acids reduced the cell viability of L. casei and L. plantarum bacteria from 108 CFU.mL-1 to 105 CFU.mL-1 and showed no effect in the growth of Saccharomyces cerevisiae. These experiments were conducted at 120 rpm and 25°C. The clear brandy production (200 L using the same alpha acids concentration (40 ppm and Saccharomyces cerevisiae cell recycling (14 times showed no contamination by bacteria. Then, the clear brandy was distilled in a 160 L cooper distiller. The clear brandy produced with and without alpha acids, was analyzed in the Laboratory of Alcohol and Beverages as well as in the Laboratory of Spectroscopy of the Cuban Research Institute of the Sugarcane Derivatives (ICIDCA in Spanish in Havana and showed similarities in their composition and sensorial chemical analysis.

INFLUENCE OF ALPHA-1-ACID GLYCOPROTEIN UPON PRODUCTION OF CYTOKINES BY PERIPHERAL BLOOD MONONUCLEARS

Directory of Open Access Journals (Sweden)

М. V. Osikov

2007-01-01

Full Text Available Abstract. Alpha-1-acid glycoprotein (orosomucoid is a multifunctional acute phase reactant belonging to the family of lipocalines from plasma alpha-2 globulin fraction. In present study, we investigated dosedependent effects of orosomucoid upon secretion of IL-1â, IL-2, IL-3, IL-4 by mononuclear cells from venous blood of healthy volunteers. Mononuclear cells were separated by means of gradient centrifugation, followed by incubation for 24 hours with 250, 500, or 1000 mcg of orosomucoid per ml RPMI-1640 medium (resp., low, medium and high dose. The levels of cytokine production were assayed by ELISA technique. Orosomucoid-induced secretion of IL-1â and IL-4 was increased, whereas IL-3 secretion was inhibited. IL-2 production was suppressed at low doses of orosomucoid, and stimulated at medium and high doses. The effect of alpha-1-acid glycoprotein upon production of IL-2, IL-3 and IL-4 was dose-dependent. Hence, these data indicate that orosomucoid is capable of modifying IL-1â, IL-2, IL-3, and IL-4 secretion by blood mononuclear cells.

Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis

DEFF Research Database (Denmark)

Andersen, U O; Kirkeby, S; Bøg-Hansen, T C

1997-01-01

Three glycoforms of alpha 1-acid glycoprotein (AGP) were biotinylated to examine their binding in mouse testis by light microscopy. The transition from one stage to another in the spermatogenic cycle is marked with an appearance of a receptor for the Concanavalin A (Con A) non-reactive glycoform...

Effects of lactic acid bacteria in kimoto on sake brewing. Part 2. ; Promotion mechanism of enzymolysis in rice by teichoic acid. Kimotochu no nyusankin no seishu jozo ni oyobosu eikyo. 2. ; Kimotochu no nyusankin ni yuraisuru teikosan no. alpha. kamai yokai sokushin sayo kisaku

Energy Technology Data Exchange (ETDEWEB)

Mizoguchi, H.; Tsurumoto, M.; Furukawa, A.; Kawasaki, T. (Kikumasamune Sake Brewing Co. Ltd, Hyogo (Japan))

1991-07-25

In order to elucidate promotion mechanism of dissolution of {alpha}-rice (pregelatinized rice) by teichoic acid. adsorption of teichoic acid and {alpha}-amylase onto rice protein oryzenin was investigated by experiments. Teichoic acid was adsorbed well onto oryzenin and reduced adsorption of {alpha}-amylase. Adsorption of {alpha}-amylase onto rice powder was decreased logarithmically in proportion to the teichoic acid added. Both teichoic acid and {alpha}-amylase were adsorbed by histone, abundant in basic amino acids, and by anion-exchange resin. Adsorption of {alpha}-amylase onto them was reduced by coexistence with teichoic acid. As the results of experiments, it was inferred that teichoic acid became dissolvable through autolysis by lactic acid bacteria in kimoto, changed the state of electric charge on oryzenin surfaces through adsorption onto oryzenin by phosphoric group, decreasing adsorption of {alpha}-amylase onto oryzenin and increasing free {alpha}-amylase in the liquid phase, and thus increased the dissolution of {alpha}-rice. 9 refs., 6 figs., 3 tabs.

The gas–liquid chromatography of carboxylic acid esters of the urinary 11-deoxy-17-oxo steroids

Science.gov (United States)

Sadler, Patricia A.; Kellie, A. E.

1967-01-01

1. The gas–liquid-chromatographic separations of the acetate, propionate, n-butyrate, isobutyrate and n-valerate esters of androsterone, aetiocholanolone and dehydroepiandrosterone were studied on a 1% neopentyl glycol sebacate column. The n-butyrate, isobutyrate and n-valerate esters were well resolved. 2. The three steroids derived from hydrolysed urinary 17-oxo steroid conjugate extracts were analysed by gas–liquid chromatography after conversion into their n-butyrate esters. The results were compared with independent determinations involving chromatography on alumina. PMID:4227802

Copper(II) 12-metallacrown-4 complexes of alpha-, beta- and gamma-aminohydroxamic acids: a comparative thermodynamic study in aqueous solution.

Science.gov (United States)

Tegoni, Matteo; Remelli, Maurizio; Bacco, Dimitri; Marchiò, Luciano; Dallavalle, Francesco

2008-05-28

A complete thermodynamic study of the protonation and Cu(II) complex formation equilibria of a series of alpha- and beta-aminohydroxamic acids in aqueous solution was performed. The thermodynamic parameters obtained for the protonation of glycine-, (S)-alpha-alanine-, (R,S)-valine-, (S)-leucine-, beta-alanine- and (R)-aspartic-beta-hydroxamic acids were compared with those previously reported for gamma-amino- and (S)-glutamic-gamma-hydroxamic acids. The enthalpy/entropy parameters calculated for the protonation microequilibria of these three types of ligands are in very good agreement with the literature values for simple amines and hydroxamic acids. The pentanuclear complexes [Cu5L4H(-4)]2+ contain the ligands acting as (NH2,N-)-(O,O-) bridging bis-chelating and correspond to 12-metallacrown-4 (12-MC-4) which are formed by self-assembly between pH 4 and 6 with alpha-aminohydroxamates (HL), while those with beta- and gamma-derivatives exist in a wider pH range (4-11). The stability order of these metallomacrocycles is beta- > alpha- > gamma-aminohydroxamates. The formation of 12-MC-4 with alpha-aminohydroxamates is entropy-driven, and that with beta-derivatives is enthalpy-driven, while with gamma-GABAhydroxamate both effects occur. These results are interpreted on the basis of specific enthalpies or entropy contributions related to chelate ring dimensions, charge neutralization and solvation-desolvation effects. The enthalpy/entropy parameters of 12-MC-4 with alpha-aminohydroxamic acids considered are also dependent on the optical purity of the ligands. Actually, that with (R,S)-valinehydroxamic acid presents an higher entropy and a lower enthalpy value than those of enantiopure ligands, although the corresponding stabilities are almost equivalent. Moreover, DFT calculations are in agreement with a more exothermic enthalpy found for metallacrowns with enantiomerically pure ligands.

Bowl adamanzanes--bicyclic tetraamines: syntheses and crystal structures of complexes with cobalt(III) and chelating coordinated oxo-anions.

Science.gov (United States)

Broge, Louise; Søtofte, Inger; Jensen, Kristian; Jensen, Nicolai; Pretzmann, Ulla; Springborg, Johan

2007-09-14

Seven cobalt(III) complexes of the macrobicyclic tetraamine ligand [2(4).3(1)]adamanzane ([2(4).3(1)]adz) are reported along with the crystal structure of six of these complexes. The solid state and solution structures are discussed, and a detailed assignment of the NMR spectra of the sulfato complex is provided. Four of the seven complexes contain a chelate coordinating oxo-anion (sulfate, formiate, nitrate, carbonate). Equilibration of these species with the corresponding diaqua complex is generally slow. The rates of equilibration in 5 mol dm(-3) perchloric acid at 25 degrees C have been measured, yielding half lives of 20 min, 10 min and 3 h for the sulfato, formiato and carbonato species respectively. The corresponding reaction for the nitrato complex occurs with a half life of less than 3 min. The concentration acid dissociation constant for the Co([2(4).3(1)]adz)(HCO(3))(2+) ion has been measured to K(a) = 0.33 mol dm(-3) [25 degrees C, I = 2 mol dm(-3)] and K(a) = 0.15 mol dm(-3) [25 degrees C, I = 5 mol dm(-3)]. The propensity for coordination of sulfate was found to be large enough for a quantitative conversion of the carbonato complex to the sulfato complex to occur in 3 mol dm(-3) triflic acid containing a small sulfate contamination. On this basis the decarboxylation in 5 mol dm(-3) triflic acid of the corresponding cobalt(III) carbonato complex of the larger macrobicyclic tetraamine ligand [3(5)]adz was reinvestigated and found to lead to the sulfato complex as well. The difference in exchange rate of the oxo-anion ligands for the cobalt(III) complexes of the two adamanzane ligands is discussed and attributed to fundamental differences in the molecular structure where an inverted configuration of the secondary non-bridged amine groups is seen for the complexes of the larger [3(5)]adz ligand. The high affinity for chelating coordination of oxo-anions for these two cobalt(iii)-adamanzane-moieties is rationalised on basis of the N-Co-N angles. N

Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation

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Harold Spedding

2017-10-01

Full Text Available Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity.

Trapping social wasps (Hymenoptera: Vespidae) with acetic acid and saturated short chain alcohols.

Science.gov (United States)

Landolt, P J; Smithhisler, C S; Reed, H C; McDonough, L M

2000-12-01

Nineteen compounds were evaluated in combination with a solution of acetic acid as baits for trapping the German yellowjacket, Vespula germanica (F.), the western yellowjacket Vespula pensylvanica (Sausssure), and the golden paper wasp Polistes aurifer Saussure. Compounds with three to six carbon chains or branched chains and with a hydroxy functional group were selected for testing based on their similarity to isobutanol. They were compared with isobutanol with acetic acid, which is a known wasp attractant. None of the compounds tested were superior to isobutanol when presented with acetic acid as a lure for these species of wasps. However, traps baited with either the S-(-)- or the racemic mixture of 2-methyl-1-butanol in combination with acetic acid captured similar numbers of both species of yellowjackets, compared with isobutanol with acetic acid. Polistes aurifer responded strongly to the S-(-)-enantiomer and to the racemic mixture of 2-methyl-1-butanol with acetic acid and not to the R-(+)-enantiomer with acetic acid.

Priming of seeds with methyl jasmonate induced resistance to hemi-biotroph Fusarium oxysporum f.sp. lycopersici in tomato via 12-oxo-phytodienoic acid, salicylic acid, and flavonol accumulation.

Science.gov (United States)

Król, P; Igielski, R; Pollmann, S; Kępczyńska, E

2015-05-01

Methyl jasmonate (MeJA) was tested by seed treatment for its ability to protect tomato seedlings against fusarium wilt caused by the soil-borne fungal pathogen Fusarium oxysporum f.sp. lycopersici. Isolated from Solanum lycopersicon L. seeds, cv. Beta fungus was identified as F. oxysporum f.sp. lycopersici Race 3 fungus by using phytopathological and molecular methods. MeJA applied at 0.01, 0.1 and 1 mM reduced spore germination and mycelial growth in vitro. Soaking of tomato seeds in MeJA solution at 0.1 mM for 1 h significantly enhanced the resistance level against the tested fungus in tomato seedlings 4 weeks after inoculation. The extracts from leaves of 15-day-old seedlings obtained from previously MeJA soaked seeds had the ability to inhibit in vitro spore germination of tested fungus. In these seedlings a significant increase in the levels phenolic compounds such as salicylic acid (SA), kaempferol and quercetin was observed. Up-regulation of phenylalanine ammonia-lyase (PAL5) and benzoic acid/salicylic acid carboxyl methyltransferase (BSMT) genes and down-regulation of the isochorysmate synthase (ICS) gene in response to exogenous MeJA application indicate that the phenylalanine ammonia-lyase (PAL), not the isochorismate (IC) pathway, is the primary route for SA production in tomato. Moreover, the increased accumulation of the flavonols quercetin and kaempferol appears closely related to the increase of PAL5, chalcone synthase (CHS) and flavonol synthase/flavanone 3-hydroxylase-like (FLS) genes. Elevated levels of salicylic acid in seedlings raised from MeJA-soaked seeds were simultaneously accompanied by a decrease of jasmonic acid, the precursor of MeJA, and an increase of 12-oxo-phytodienoic acid (OPDA), the precursor of jasmonic acid. The present results indicate that the priming of tomato seeds with 0.1mM MeJA before sowing enables the seedlings grown from these seeds to reduce the attack of the soil-borne fungal pathogen F. oxysporum f.sp. lycopersici

Mechanism of long chain monoenoic fatty acids acting on the energy metabolism of heart

Energy Technology Data Exchange (ETDEWEB)

Buddecke, E; Filipovic, I; Wortberg, B; Seher, A

1975-01-01

The oxidation of 1-/sup 14/C-erucic (Csub(22:1)) and 1-/sup 14/C-nervonic (Csub(24:1)) acid was studied compared to 1-/sup 14/C-palmitic and -oleic acid in isolated rat and pig heart mitochondria. After mitochondrial incubation with the albumin-bound fatty acids only small amounts of /sup 14/CO/sub 2/ developed from the oxidation of the long chain monoenoic acids as compared to palmitic or oleic acid. The slow down of the oxidation rate was more pronounced in rat than in pig heart mitochondria. The oxidation of palmitic or oleic acid was not found to be inhibited by the C/sub 20/-C/sub 24/-monoeneic acids, whereas palmitic or oleic acid inhibited the oxidation of erucic acid competitively. From present findings an idea may be developed of the interference on fatty acid metabolism in heart muscle by erucic and other long chain monenoic acids.

Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with preference for basic amino acids

DEFF Research Database (Denmark)

Wellendorph, Petrine; Hansen, Kasper B; Balsgaard, Anders

2005-01-01

with the signal transducing transmembrane and C terminus of the homologous goldfish 5.24 receptor allowed us to overcome these obstacles. Homology modeling of the hGPRC6A ATD based on the crystal structure of the metabotropic glutamate receptor subtype 1 predicted interaction with alpha-amino acids...

Structure effects in the region of superheavy elements via the alpha-decay chain of sup 2 sup 9 sup 3 118

CERN Document Server

Gupta, R K; Kumar, R; Balasubramaniam, M; Scheid, W

2002-01-01

The alpha-decay chain of sup 2 sup 9 sup 3 118, first proposed in the Berkeley cold fusion experiment sup 2 sup 0 sup 8 Pb( sup 8 sup 6 Kr, 1n) and now retracted, is calculated by using the preformed cluster model (PCM) of one of the authors (RKG). Also, the possible branchings of alpha-decays to heavier cluster decays of all the parents in this chain are calculated for the first time. The calculated Q-values, penetrabilities and preformation factors for alpha-decays suggest that the sup 2 sup 8 sup 5 114 nucleus with Z=114, N=171 is a magic nucleus, either due to the magicity of Z=114, or N=172 or both. The N=172 is proposed to be a magic number in certain relativistic mean-field calculations, but with Z 120. The calculated cluster decays point to new interesting possibilities of sup 1 sup 4 C decay of the sup 2 sup 8 sup 1 112 parent, giving rise to a (reasonably) deformed Z=106, N=161, sup 2 sup 6 sup 7 106 daughter (N=162 being now established as the deformed magic shell) or to a doubly magic sup 4 sup 8 ...

Metabolism of very long-chain Fatty acids: genes and pathophysiology.

Science.gov (United States)

Sassa, Takayuki; Kihara, Akio

2014-02-01

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.

8-Oxo-7,8-dihydroadenine and 8-Oxo-7,8-dihydroadenosine-Chemistry, Structure, and Function in RNA and Their Presence in Natural Products and Potential Drug Derivatives.

Science.gov (United States)

Choi, Yu Jung; Chang, Stephanie J; Gibala, Krzysztof S; Resendiz, Marino J E

2017-05-17

A description and history of the role that 8-oxo-7,8-dihydroadenine (8-oxoAde) and 8-oxo-7,8-dihydroadenosine (8-oxoA) have in various fields has been compiled. This Review focusses on 1) the formation of this oxidatively generated modification in RNA, its interactions with other biopolymers, and its potential role in the development/progression of disease; 2) the independent synthesis and incorporation of this modified nucleoside into oligonucleotides of RNA to display the progress that has been made in establishing its behavior in biologically relevant systems; 3) reported synthetic routes, which date back to 1890, along with the progress that has been made in the total synthesis of the nucleobase, nucleoside, and their corresponding derivatives; and 4) the isolation, total synthesis, and biological activity of natural products containing these moieties as the backbone. The current state of research regarding this oxidatively generated lesion as well as its importance in the context of RNA, natural products, and potential as drug derivatives is illustrated using all available examples reported to date. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo studies of the biosynthesis of alpha-eleostearic acid in the seed of Momordica charantia L

International Nuclear Information System (INIS)

Liu, L.; Hammond, E.G.; Nikolau, B.J.

1997-01-01

In vivo radiotracer experiments using 14C-labeled acetate, oleate, linoleate, and linolenate were conducted to investigate the biosynthesis of alpha-eleostearic acid in the seeds of Momordica charantia. With the exception of [14C]linolenate, all of these precursors radioactively labeled alpha-eleostearate. Kinetics of the time course of metabolism of the radioactive precursors indicate that linoleate is the acyl precursor of alpha-eleostearate and that its conversion to alpha-eleostearate occurs while the acyl moiety is esterified to PC. Pulse-chase experiments with 14C-labeled acetate or linoleate provided additional corroborative evidence that linoleoyl PC is the precursor of alpha-eleostearoyl PC

cPLA2alpha-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic beta-cells

DEFF Research Database (Denmark)

Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L

2003-01-01

Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2alpha) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. cPLA2alpha...... from 70-80 to 280-300. cPLA2alpha-stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2alpha. The action of cPLA2alpha was mimicked by a combination...... of arachidonic acid and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2alpha was inhibited...

Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

International Nuclear Information System (INIS)

May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

1987-01-01

Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH 4 Cl x 100 g body wt -1 x day -1 . Epitrochlearis muscles were incubated with L-[1- 14 C]-valine and L-[1- 14 C]leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain α-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain α-keto acid dehydrogenase

Zinc absorption in experimental osmotic diarrhea: effect of long-chain fatty acids.

Science.gov (United States)

Lee, S Y; Wapnir, R A

1993-03-01

The effect of free fatty acids on zinc absorption was studied in a rat model of chronic osmotic diarrhea induced with magnesium citrate and phenolphthalein. In vivo rates of zinc removal from the lumen and analysis of tissue for zinc uptake and metallothionein alterations were monitored. One mmol/L stearate enhanced zinc absorption in rats with or without diarrhea, from 207 +/- 22 and 353 +/- 13 pmol/min x cm to 676 +/- 34 and 610 +/- 26 pmol/min x cm, respectively. Palmitate was only effective in normal rats. Zinc absorption inversely correlated with mucosal zinc content in the perfused intestinal segments, in both type of rats. Hepatic metallothionein was enhanced by zinc and even more by oleate plus zinc in both groups; kidney metallothionein in animals with diarrhea was normalized by either oleate or zinc. The data support previous reports on the effect of long-chain fatty acids on the enhancement of zinc absorption: saturation and a longer chain appear to be positive factors. A membrane modification role of long-chain fatty acids could have nutritional implications in the formulation of special diets.

Chemical mechanical polishing of hard disk substrate with {alpha}-alumina-g-polystyrene sulfonic acid composite abrasive

Energy Technology Data Exchange (ETDEWEB)

Lei Hong, E-mail: hong_lei2005@yahoo.com.c [Research Center of Nano-science and Nano-technology, Shanghai University, Shanghai 200444 (China); Bu Naijing; Chen Ruling; Hao Ping [Research Center of Nano-science and Nano-technology, Shanghai University, Shanghai 200444 (China); Neng Sima; Tu Xifu; Yuen Kwok [Shenzhen Kaifa Magnetic Recording Co., LTD, Shenzhen, 518035 (China)

2010-05-03

{alpha}-Alumina-g-polystyrene sulfonic acid ({alpha}-Al{sub 2}O{sub 3}-g-PSS) composite abrasive was prepared by surface activation, graft polymerization and sulfonation, successively. The composition, dispersibility and morphology of the product were characterized by Fourier transformed infrared spectroscopy, laser particle size analysis and scanning electron microscopy, respectively. The chemical mechanical polishing (CMP) performances of the composite abrasive on hard disk substrate with nickel-phosphorous plating were investigated. The microscopy images of the polished surfaces show that {alpha}-Al{sub 2}O{sub 3}-g-PSS composite abrasive results in improved CMP and post-CMP cleaning performances than pure {alpha}-alumina abrasive under the same testing conditions.

Structure of the T cell receptor in a Ti alpha V beta 2, alpha V beta 8-positive T cell line

DEFF Research Database (Denmark)

Hou, X; Dietrich, J; Kuhlmann, J

1994-01-01

not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association......The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still...... with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti...

An exceptional series of phase transitions in hydrophobic amino acids with linear side chains

Directory of Open Access Journals (Sweden)

Carl Henrik Görbitz

2016-09-01

Full Text Available The solid-state phase transitions and intermediate structures of S-2-aminobutanoic acid (l-2-aminobutyric acid, S-2-aminopentanoic acid (l-norvaline, S-2-aminohexanoic acid (l-norleucine and l-methionine between 100 and 470 K, identified by differential scanning calorimetry, have been characterized in a comprehensive single-crystal X-ray diffraction investigation. Unlike other enantiomeric amino acids investigated until now, this group featuring linear side chains displays up to five distinct phases. The multiple transitions between them involve a number of different processes: alteration of the hydrogen-bond pattern, to our knowledge the first example of this observed for an amino acid, sliding of molecular bilayers, seen previously only for racemates and quasiracemates, concerted side-chain rearrangements and abrupt as well as gradual modifications of the side-chain disorder. Ordering of l-norleucine upon cooling even proceeds via an incommensurately modulated structure. l-Methionine has previously been described as being fully ordered at room temperature. An accurate refinement now reveals extensive disorder for both molecules in the asymmetric unit, while two previously unknown phases occur above room temperature.

Regioselectively nucleus and/or side-chain fluorinated 2-(Phenanthryl)propionic acids by an effective combination of radical and organometallic chemistry.

Science.gov (United States)

Ricci, Giacomo; Ruzziconi, Renzo

2005-01-21

Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a-c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a-c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting beta-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a-c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110 degrees C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3-difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above alpha-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl)propionic acids 1-5 to be obtained in satisfactory overall yields.

Asimetric synthesis of alpha-phenyl amino acids; Sintesis asimetrica de alfa-fenilaminoacidos

Energy Technology Data Exchange (ETDEWEB)

Caltiviela, C.; Diaz de Villegas, M.D.; Galvez, J.A.; Lapena, Y. [Departamento de Quimica Organica, Universidad de Zaragoza, Zaragoza (Spain)

1994-12-31

A new synthetic strategy to obtain alpha-phenyl amino acids in enantiomerically pure form is described. The new route is based on the highly diastereoselective alkylation of (1S,2R,4R)-10-dicyclohexylsulfamoylisobornyl 2-phenylcianoacetate and subsequent curtis type rearrangement of the alkylated compound with total retention of configuration. 17 refs

No need to be HAMLET or BAMLET to interact with histones: binding of monomeric alpha-lactalbumin to histones and basic poly-amino acids.

Science.gov (United States)

Permyakov, Serge E; Pershikova, Irina V; Khokhlova, Tatyana I; Uversky, Vladimir N; Permyakov, Eugene A

2004-05-18

The ability of a specific complex of human alpha-lactalbumin with oleic acid (HAMLET) to induce cell death with selectivity for tumor and undifferentiated cells was shown recently to be mediated by interaction of HAMLET with histone proteins irreversibly disrupting chromatin structure [Duringer, C., et al. (2003) J. Biol. Chem. 278, 42131-42135]. Here we show that monomeric alpha-lactalbumin (alpha-LA) in the absence of fatty acids is also able to bind efficiently to the primary target of HAMLET, histone HIII, regardless of Ca(2+) content. Thus, the modification of alpha-LA by oleic acid is not required for binding to histones. We suggest that interaction of negatively charged alpha-LA with the basic histone stabilizes apo-alpha-LA and destabilizes the Ca(2+)-bound protein due to compensation for excess negative charge of alpha-LA's Ca(2+)-binding loop by positively charged residues of the histone. Spectrofluorimetric curves of titration of alpha-LA by histone H3 were well approximated by a scheme of cooperative binding of four alpha-LA molecules per molecule of histone, with an equilibrium dissociation constant of 1.0 microM. Such a stoichiometry of binding implies that the binding process is not site-specific with respect to histone and likely is driven by just electrostatic interactions. Co-incubation of positively charged poly-amino acids (poly-Lys and poly-Arg) with alpha-LA resulted in effects which were similar to those caused by histone HIII, confirming the electrostatic nature of the alpha-LA-histone interaction. In all cases that were studied, the binding was accompanied by aggregation. The data indicate that alpha-lactalbumin can be used as a basis for the design of antitumor agents, acting through disorganization of chromatin structure due to interaction between alpha-LA and histone proteins.

Subcritical Water Hydrolysis of Peptides: Amino Acid Side-Chain Modifications

Science.gov (United States)

Powell, Thomas; Bowra, Steve; Cooper, Helen J.

2017-09-01

Previously we have shown that subcritical water may be used as an alternative to enzymatic digestion in the proteolysis of proteins for bottom-up proteomics. Subcritical water hydrolysis of proteins was shown to result in protein sequence coverages greater than or equal to that obtained following digestion with trypsin; however, the percentage of peptide spectral matches for the samples treated with trypsin were consistently greater than for those treated with subcritical water. This observation suggests that in addition to cleavage of the peptide bond, subcritical water treatment results in other hydrolysis products, possibly due to modifications of amino acid side chains. Here, a model peptide comprising all common amino acid residues (VQSIKCADFLHYMENPTWGR) and two further model peptides (VCFQYMDRGDR and VQSIKADFLHYENPTWGR) were treated with subcritical water with the aim of probing any induced amino acid side-chain modifications. The hydrolysis products were analyzed by direct infusion electrospray tandem mass spectrometry, either collision-induced dissociation or electron transfer dissociation, and liquid chromatography collision-induced dissociation tandem mass spectrometry. The results show preferential oxidation of cysteine to sulfinic and sulfonic acid, and oxidation of methionine. In the absence of cysteine and methionine, oxidation of tryptophan was observed. In addition, water loss from aspartic acid and C-terminal amidation were observed in harsher subcritical water conditions. [Figure not available: see fulltext.

Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex

DEFF Research Database (Denmark)

Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

1999-01-01

receptor was located in the cytoplasm of glomerulosa and outer fasciculata cells. The intensity of the reaction product decreased in the fasciculata, and no staining was seen in inner fasciculata and reticularis. Inhibition with the simple sugars, mannose and GlcNAc confirmed a lectin-like reaction...... specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution...

Branched-chain alpha-keto acid catabolism via the gene products of the bkd operon in Enterococcus faecalis: a ne, secreted metabolite serving as a temporary redox sink.

NARCIS (Netherlands)

Ward, D.E.; van der Weijden, C.C.; van der Merwe, M.J.; Westerhoff, H.V.; Claiborne, A.; Snoep, J.L.

2000-01-01

Recently the bkd gene cluster from Enterococcus faecalis was sequenced, and it was shown that the gene products constitute a pathway for the catabolism of branched-chain α-keto acids. We have now investigated the regulation and physiological role of this pathway. Primer extension analysis identified

Titanium oxo-clusters: precursors for a Lego-like construction of nanostructured hybrid materials.

Science.gov (United States)

Rozes, Laurence; Sanchez, Clément

2011-02-01

Titanium oxo-clusters, well-defined monodispersed nano-objects, are appropriate nano-building blocks for the preparation of organic-inorganic materials by a bottom up approach. This critical review proposes to present the different structures of titanium oxo-clusters referenced in the literature and the different strategies followed to build up hybrid materials with these versatile building units. In particular, this critical review cites and reports on the most important papers in the literature, concentrating on recent developments in the field of synthesis, characterization, and the use of titanium oxo-clusters for the construction of advanced hybrid materials (137 references).

Effectiveness and Mechanisms of Antagonism of Toxic Effects of Cyanide by Alpha-Keto Acids.

Science.gov (United States)

1986-12-31

until the miss-w near death. Lethal blood levels of cyanide in alpha-KG treated animl. as levels of 5-7 mcg cyani0e, which so 5-7 times the expected...lethal levels . rwm these studies, alpha-KC is effettive in antagonising administered dos of CH of five time the lethal dose before the toxic effects are...parameters in the dog .................. 26 Table 6 The effects of cyanide on 2,3 diphosphoglyceric acid .......... 28 Table 7 Stability of solution of ci

Effect of alpha-lipoic acid on endometrial implants in an experimental rat model.

Science.gov (United States)

Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Özgür, Tümay; Bayraktar, Suphi

2017-10-01

To investigate the antioxidant and anti-inflammatory effects of alpha-lipoic acid (ALA) in the treatment of endometriosis in an experimental rat model by evaluating biochemical and histopathologic parameters. Experimental endometriosis was induced by the peritoneal implantation of autologous endometrial tissue. The rats were randomly divided into two groups with eight rats each. Group I was intraperitoneally administered ALA 100 mg/kg/day for 14 days. Group II was intraperitoneally administered saline solution at the same dosage and over the same period. Endometrial implant volume was measured in both groups both pre- and post-treatment. Tumor necrosis factor alpha (TNF-α) was measured in peritoneal fluid. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were assessed in serum. The implants were histopathologically evaluated. In the ALA group, the serum TOS and OSI levels, the endometrial implant volumes, the TNF-α levels in serum and peritoneal fluid, and the histopathologic scores were significantly lower compared to the control group (P < 0.05). Alpha-lipoic acid may have a therapeutic potential in the treatment of endometriosis due to its antioxidant and anti-inflammatory effects. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

DEFF Research Database (Denmark)

Jakobsen, Marianne Uhre; Dethlefsen, Claus; Due, Karen Margrete

2011-01-01

We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers.......We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers....

Synthesis of deuterium-labeled analogs of the lipid hydroperoxide-derived bifunctional electrophile 4-oxo-2(E)-nonenal

OpenAIRE

Arora, Jasbir S.; Oe, Tomoyuki; Blair, Ian A.

2011-01-01

Lipid hydroperoxides undergo homolytic decomposition into the bifunctional 4-hydroxy-2(E)-nonenal and 4-oxo-2(E)-nonenal (ONE). These bifunctional electrophiles are highly reactive and can readily modify intracellular molecules including glutathione (GSH), deoxyribonucleic acid (DNA) and proteins. Lipid hydroperoxide-derived bifunctional electrophiles are thought to contribute to the pathogenesis of a number of diseases. ONE is an α,β-unsaturated aldehyde that can react in multiple ways and w...

On the diffusion of alpha-helical proteins in solvents

Science.gov (United States)

Barredo, Wilson I.; Bornales, Jinky B.; Bernido, Christopher C.; Aringa, Henry P.

2015-01-01

The winding probability function for a biopolymer diffusing in a crowded cell is obtained with the drift coefficient f(s) involving Bessel functions of general form f(s) = kJ2p+1 (νs). The variable s is the length along the chain and ν is a constant which can be used to simulate the frequency of appearance of a certain type of amino acid. Application of a particular case p = 3 to protein chains is carried out for different alpha helical proteins found in the Protein Data Bank (PDB). Analysis of our results leads us to an empirical formula that can be used to conveniently predict k/D and ν, where D is the diffusion coefficient of various α-helical proteins in solvents.

Time-resolved fluorescence sensing of N-acetyl amino acids, nucleobases, nucleotides and DNA by the luminescent Tb (III) - 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde probe

Energy Technology Data Exchange (ETDEWEB)

Azab, Hassan A. [Chemistry Department, Faculty of Science, Suez Canal University, 41522 Ismailia (Egypt); Khairy, Gasser M., E-mail: gasser_chemist@yahoo.com [Chemistry Department, Faculty of Science and Arts, Aljouf University, P.O. Box # 2014, Skaka 41421 (Saudi Arabia); Chemistry Department, Faculty of Science, Suez Canal University, 41522 Ismailia (Egypt); Abd El-Ghany, N.; Ahmed, Marwa A. [Chemistry Department, Faculty of Science, Suez Canal University, El-Arish (Egypt)

2016-08-15

A time-resolved (gated) luminescence-based method for the detection of some of N-acetyl amino acids, nucleobases, nucleotides, and DNA using terbium- 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde (AOCC) complex in 1:2 metal: ligand ratio in microtiterplate format has been evolved. The linear range for determination of the selected biomolecules is 0.1–1.0 µM. The detection limit was in the range of 0.0371–0.106 µM. The thermodynamic parameters, and binding constants (K) of N-acetyl amino acids, nucleobases, nucleotides with Tb (III) –(AOCC) {sub 2} complex were calculated. Positive and negative values of entropy (ΔS) and enthalpy (ΔH) changes for Tb (III) –(AOCC){sub 2}– N-acetyl amino acids, nucleobases or nucleotides ternary complexes were evaluated. Selectivity of Tb (III) -complex towards different biomolecules has been studied using ratiometric methods of analysis by comparison of biomolecules binding affinities for Tb (III) -complex. Interaction of Tb (III) complex with DNA has been studied.

Time-resolved fluorescence sensing of N-acetyl amino acids, nucleobases, nucleotides and DNA by the luminescent Tb (III) - 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde probe

International Nuclear Information System (INIS)

Azab, Hassan A.; Khairy, Gasser M.; Abd El-Ghany, N.; Ahmed, Marwa A.

2016-01-01

A time-resolved (gated) luminescence-based method for the detection of some of N-acetyl amino acids, nucleobases, nucleotides, and DNA using terbium- 8-alkyl-2-oxo-2H-chromene-3-carbaldehyde (AOCC) complex in 1:2 metal: ligand ratio in microtiterplate format has been evolved. The linear range for determination of the selected biomolecules is 0.1–1.0 µM. The detection limit was in the range of 0.0371–0.106 µM. The thermodynamic parameters, and binding constants (K) of N-acetyl amino acids, nucleobases, nucleotides with Tb (III) –(AOCC) 2 complex were calculated. Positive and negative values of entropy (ΔS) and enthalpy (ΔH) changes for Tb (III) –(AOCC) 2 – N-acetyl amino acids, nucleobases or nucleotides ternary complexes were evaluated. Selectivity of Tb (III) -complex towards different biomolecules has been studied using ratiometric methods of analysis by comparison of biomolecules binding affinities for Tb (III) -complex. Interaction of Tb (III) complex with DNA has been studied.

Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

International Nuclear Information System (INIS)

Chiba, S.; Shibuya, K.; Miyazono, K.; Tojo, A.; Oka, Y.; Miyagawa, K.; Takaku, F.

1990-01-01

The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of 125 I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB- 125 I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein

Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

KAUST Repository

Chen, Hao; Saksa, Kristen; Zhao, Feiyi; Qiu, Joyce; Xiong, Liming

2010-01-01

The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants

Saponification of esters of chiral alpha-amino acids anchored through their amine function on solid support.

Science.gov (United States)

Cantel, Sonia; Desgranges, Stéphane; Martinez, Jean; Fehrentz, Jean-Alain

2004-06-01

Anchoring an alpha-amino acid residue by its amine function onto a solid support is an alternative to develop chemistry on its carboxylic function. This strategy can involve the use of amino-acid esters as precursors of the carboxylic function. A complete study on the Wang-resin was performed to determine the non racemizing saponification conditions of anchored alpha-amino esters. The use of LiOH, NaOH, NaOSi(Me)3, various solvents and temperatures were tested for this reaction. After saponification and cleavage from the support, samples were examined through their Marfey's derivatives by reversed phase HPLC to evaluate the percentage of racemization.

Medium-chain fatty acid binding to albumin and transfer to phospholipid bilayers

International Nuclear Information System (INIS)

Hamilton, J.A.

1989-01-01

Temperature-dependent (5-42 degree C) 13 C NMR spectra of albumin complexes with 90% isotopically substituted [1- 13 C]octanoic or [1- 13 C]decanoic acids showed a single peak at >30 degree C but three peaks at lower temperatures. The chemical-shift differences result from different ionic and/or hydrogen-bonding interactions between amino acid side chains and the fatty acid carboxyl carbon. Rapid exchange of fatty acid among binding sites obscures these sites at temperatures >30 degree C. Rate constants for exchange at 33 degree C were 350 sec -1 for octanoate and 20 sec -1 for decanoate. Temperature-dependent data for octanoate showed an activation energy of 2 kcal/mol for exchange. Spectra of albumin complexes with the 12-carbon saturated fatty acid, lauric acid, had several narrow laurate carboxyl peaks at 35 degree C, indicating longer lifetimes in the different binding sites. Fatty acid exchange between albumin and model membranes (phosphatidylcholine bilayers) occurred on a time scale comparable to that for exchange among albumin binding sites, following the order octanoate > decanoate > laurate. The equilibrium distribution of fatty acid between lipid bilayers and protein was measured directly from NMR spectra. Decreasing pH increased the relative affinity of fatty acid for the lipid bilayer. The results predict that the relative affinity of octanoic acid for albumin and membranes will be similar to that of long-chain fatty acids, but the rate of equilibration will be ∼ 10 4 faster for octanoic acid

Activity of 3-Ketosteroid 9α-Hydroxylase (KshAB) Indicates Cholesterol Side Chain and Ring Degradation Occur Simultaneously in Mycobacterium tuberculosis*

Science.gov (United States)

Capyk, Jenna K.; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C.; Eltis, Lindsay D.

2011-01-01

Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (kcat/Km) of KshAB for the CoA thioester substrates was 20–30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent KmO2 was 90 ± 10 μm in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ1 ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism. PMID:21987574

Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis.

Science.gov (United States)

Capyk, Jenna K; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C; Eltis, Lindsay D

2011-11-25

Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (k(cat)/K(m)) of KshAB for the CoA thioester substrates was 20-30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent K(m)(O(2)) was 90 ± 10 μM in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ(1) ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism.

Branched Chain Amino Acid Oxidation in Cultured Rat Skeletal Muscle Cells

Science.gov (United States)

Pardridge, William M.; Casanello-Ertl, Delia; Duducgian-Vartavarian, Luiza

1980-01-01

Leucine metabolism in skeletal muscle is linked to protein turnover. Since clofibrate is known both to cause myopathy and to decrease muscle protein content, the present investigations were designed to examine the effects of acute clofibrate treatment on leucine oxidation. Rat skeletal muscle cells in tissue culture were used in these studies because cultivated skeletal muscle cells, like muscle in vivo, have been shown to actively utilize branched chain amino acids and to produce alanine. The conversion of [1-14C]leucine to 14CO2 or to the [1-14C]keto-acid of leucine (α-keto-isocaproate) was linear for at least 2 h of incubation; the production of 14CO2 from [1-14C]leucine was saturable with a Km = 6.3 mM and a maximum oxidation rate (Vmax) = 31 nmol/mg protein per 120 min. Clofibric acid selectively inhibited the oxidation of [1-14C]leucine (Ki = 0.85 mM) and [U-14C]isoleucine, but had no effect on the oxidation of [U-14C]glutamate, -alanine, -lactate, or -palmitate. The inhibition of [1-14C]leucine oxidation by clofibrate was also observed in the rat quarter-diaphragm preparation. Clofibrate primarily inhibited the production of 14CO2 and had relatively little effect on the production of [1-14C]keto-acid of leucine. A physiological concentration—3.0 g/100 ml—of albumin, which actively binds clofibric acid, inhibited but did not abolish the effects of a 2-mM concentration of clofibric acid on leucine oxidation. Clofibrate treatment stimulated the net consumption of pyruvate, and inhibited the net production of alanine. The drug also increased the cytosolic NADH/NAD+ ratio as reflected by an increase in the lactate/pyruvate ratio, in association with a decrease in cell aspartate levels. The changes in pyruvate metabolism and cell redox state induced by the drug were delayed compared with the nearly immediate inhibition of leucine oxidation. These studies suggest that clofibric acid, in concentrations that approximate high therapeutic levels of the drug

Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes.

Science.gov (United States)

Du, X; Edelstein, D; Brownlee, M

2008-10-01

We determined whether fixed doses of benfotiamine in combination with slow-release alpha-lipoic acid normalise markers of reactive oxygen species-induced pathways of complications in humans. Male participants with and without type 1 diabetes were studied in the General Clinical Research Centre of the Albert Einstein College of Medicine. Glycaemic status was assessed by measuring baseline values of three different indicators of hyperglycaemia. Intracellular AGE formation, hexosamine pathway activity and prostacyclin synthase activity were measured initially, and after 2 and 4 weeks of treatment. In the nine participants with type 1 diabetes, treatment had no effect on any of the three indicators used to assess hyperglycaemia. However, treatment with benfotiamine plus alpha-lipoic acid completely normalised increased AGE formation, reduced increased monocyte hexosamine-modified proteins by 40% and normalised the 70% decrease in prostacyclin synthase activity from 1,709 +/- 586 pg/ml 6-keto-prostaglandin F(1alpha) to 4,696 +/- 533 pg/ml. These results show that the previously demonstrated beneficial effects of these agents on complication-causing pathways in rodent models of diabetic complications also occur in humans with type 1 diabetes.

Ethylmalonic aciduria is associated with an amino acid variant of short chain acyl-coenzyme A dehydrogenase

DEFF Research Database (Denmark)

Corydon, M J; Gregersen, N; Lehnert, W

1996-01-01

Ethylmalonic aciduria is a common biochemical finding in patients with inborn errors of short chain fatty acid beta-oxidation. The urinary excretion of ethylmalonic acid (EMA) may stem from decreased oxidation by short chain acyl-CoA dehydrogenase (SCAD) of butyryl-CoA, which is alternatively...

Homoserine as an Aspartic Acid Precursor for Synthesis of Proteoglycan Glycopeptide Containing Aspartic Acid and Sulfated Glycan Chain

OpenAIRE

Yang, Weizhun; Ramadan, Sherif; Yang, Bo; Yoshida, Keisuke; Huang, Xuefei

2016-01-01

Among many hurdles in synthesizing proteoglycan glycopeptides, one challenge is the incorporation of aspartic acid in the peptide backbone and acid sensitive O-sulfated glycan chains. To overcome this, a new strategy was developed utilizing homoserine as an aspartic acid precursor. The conversion of homoserine to aspartic acid in the glycopeptide was successfully accomplished by late stage oxidation using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and bis(acetoxy)iodobenzene (BAIB). This is...

Crystal structures of hibiscus acid and hibiscus acid dimethyl ester isolated from Hibiscus sabdariffa (Malvaceae).

Science.gov (United States)

Zheoat, Ahmed M; Gray, Alexander I; Igoli, John O; Kennedy, Alan R; Ferro, Valerie A

2017-09-01

The biologically active title compounds have been isolated from Hibiscus sabdariffa plants, hibiscus acid as a dimethyl sulfoxide monosolvate [systematic name: (2 S ,3 R )-3-hy-droxy-5-oxo-2,3,4,5-tetra-hydro-furan-2,3-di-carb-oxy-lic acid dimethyl sulfoxide monosolvate], C 6 H 6 O 7 ·C 2 H 6 OS, (I), and hibiscus acid dimethyl ester [systematic name: dimethyl (2 S ,3 R )-3-hy-droxy-5-oxo-2,3,4,5-tetra-hydro-furan-2,3-di-carboxyl-ate], C 8 H 10 O 7 , (II). Compound (I) forms a layered structure with alternating layers of lactone and solvent mol-ecules, that include a two-dimensional hydrogen-bonding construct. Compound (II) has two crystallographically independent and conformationally similar mol-ecules per asymmetric unit and forms a one-dimensional hydrogen-bonding construct. The known absolute configuration for both compounds has been confirmed.

Diversion of phagosome trafficking by pathogenic Rhodococcus equi depends on mycolic acid chain length.

Science.gov (United States)

Sydor, Tobias; von Bargen, Kristine; Hsu, Fong-Fu; Huth, Gitta; Holst, Otto; Wohlmann, Jens; Becken, Ulrike; Dykstra, Tobias; Söhl, Kristina; Lindner, Buko; Prescott, John F; Schaible, Ulrich E; Utermöhlen, Olaf; Haas, Albert

2013-03-01

Rhodococcus equi is a close relative of Mycobacterium spp. and a facultative intracellular pathogen which arrests phagosome maturation in macrophages before the late endocytic stage. We have screened a transposon mutant library of R. equi for mutants with decreased capability to prevent phagolysosome formation. This screen yielded a mutant in the gene for β-ketoacyl-(acyl carrier protein)-synthase A (KasA), a key enzyme of the long-chain mycolic acid synthesizing FAS-II system. The longest kasA mutant mycolic acid chains were 10 carbon units shorter than those of wild-type bacteria. Coating of non-pathogenic E. coli with purified wild-type trehalose dimycolate reduced phagolysosome formation substantially which was not the case with shorter kasA mutant-derived trehalose dimycolate. The mutant was moderately attenuated in macrophages and in a mouse infection model, but was fully cytotoxic.Whereas loss of KasA is lethal in mycobacteria, R. equi kasA mutant multiplication in broth was normal proving that long-chain mycolic acid compounds are not necessarily required for cellular integrity and viability of the bacteria that typically produce them. This study demonstrates a central role of mycolic acid chain length in diversion of trafficking by R. equi. © 2012 Blackwell Publishing Ltd.

Self-assembly of long chain fatty acids: Effect of a methyl branch

DEFF Research Database (Denmark)

Liljeblad, Jonathan F. D.; Tyrode, Eric; Thormann, Esben

2014-01-01

chains of the straight chain fatty acids appear to be oriented perpendicular to the sample surface, based on an orientational analysis of VSFS data and the odd/even effect. In addition, the selection of the subphase (neat water or CdCl2 containing water buffered to pH 6.0) used for the LB-deposition has...

QUAFRINOIC ACIDS: TWO NEW TRITERPENIODS FROM ...

African Journals Online (AJOL)

From the stem bark of Quassia africana, two new triterpenoids with the ursolic acid skeleton, characterized as 3-oxo-urs-12-en-27a, 28di-oic acid and its dihydro derivative, 3β-urs-12-en-27α, 28di-oic acid have been isolated. The structures were determined using spectroscopic techniques. KEY WORDS: Quassia africana; ...

IR, FT-ICR-MS studies on (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt.

Science.gov (United States)

Lin, Zhiwei

2014-01-01

The infrared spectra of (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt (CLF-HCl) were studied and compared with free base. Their fragmentation pathways were investigated using tandem mass spectrometric (MS/MS) techniques on Fourier-transform ion cyclotron resonance spectrum, and many characteristic fragment ions were found. Copyright © 2013 Elsevier B.V. All rights reserved.

Triterpene Esters: Natural Products from Dorstenia arifolia (Moraceae

Directory of Open Access Journals (Sweden)

Maria Auxiliadora C. Kaplan

2013-04-01

Full Text Available The phytochemical study of Dorstenia arifolia Lam. (Moraceae has led to the identification of 18 triterpenes esterified by fatty acids, five triterpenes without esterification, 12 triterpenes esterified by acetic acid, together with a known furanocoumarin: α-amyrin (1, β-amyrin (2 α-amyrin acetate (3 β-amyrin acetate (4, α-amyrin octanoate (5, β-amyrin octanoate (6, α-amyrin decanoate (7, β-amyrin decanoate (8, α-amyrin dodecanoate (9, β-amyrin dodecanoate (10, α-amyrin tetradecanoate (11, β-amyrin tetradecanoate (12, α-amyrin hexadecanoate (13, β-amyrin hexadecanoate (14, glutinol (15, glutinyl acetate (16, 11-oxo-α-amyrin (17, 11-oxo-β-amyrin (18, 11-oxo-α-amyrin acetate (19, 11-oxo-β-amyrin acetate (20 11-oxo-α-amyrin octanoate (21 11-oxo-β-amyrin octanoate (22, 11-oxo-α-amyrin decanoate (23, 11-oxo-β-amyrin decanoate (24 11-oxo-α-amyrin dodecanoate (25 11-oxo-β-amyrin dodecanoate (26, ursa-9(11,12-dien-3-yl acetate (27, oleana-9(11,12-dien-3-yl acetate (28, ursa-9(11,12-dien-3-yl decanoate (29, oleana-9(11,12-dien-3-yl decanoate (30, 12,13-epoxyolean-3-yl acetate (31, 12,13-epoxyolean-9(11en-3-yl acetate (32, taraxeryl acetate (33, lupenyl acetate (34, lanosta-8,24-dien-3-yl acetate (35 and psoralen (36. The identification of the triterpene compounds isolated as isomeric mixtures obtained from the hexane extract was based mainly in mass spectra and 13C-NMR data. The long-chain alkanoic acid esters of the triterpenes α- and β-amyrin; 11-oxo-α- and 11-oxo-β-amyrin; ursa- and olean-9(11,12-dien-3-yl; have not been reported before in the literature as constituents of the Dorstenia genus.

Physcomitrella patens activates reinforcement of the cell wall, programmed cell death and accumulation of evolutionary conserved defence signals, such as salicylic acid and 12-oxo-phytodienoic acid, but not jasmonic acid, upon Botrytis cinerea infection.

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Ponce De León, Inés; Schmelz, Eric A; Gaggero, Carina; Castro, Alexandra; Álvarez, Alfonso; Montesano, Marcos

2012-10-01

The moss Physcomitrella patens is an evolutionarily basal model system suitable for the analysis of plant defence responses activated after pathogen assault. Upon infection with the necrotroph Botrytis cinerea, several defence mechanisms are induced in P. patens, including the fortification of the plant cell wall by the incorporation of phenolic compounds and the induced expression of related genes. Botrytis cinerea infection also activates the accumulation of reactive oxygen species and cell death with hallmarks of programmed cell death in moss tissues. Salicylic acid (SA) levels also increase after fungal infection, and treatment with SA enhances transcript accumulation of the defence gene phenylalanine ammonia-lyase (PAL) in P. patens colonies. The expression levels of the genes involved in 12-oxo-phytodienoic acid (OPDA) synthesis, including lipoxygenase (LOX) and allene oxide synthase (AOS), increase in P. patens gametophytes after pathogen assault, together with a rise in free linolenic acid and OPDA concentrations. However, jasmonic acid (JA) could not be detected in healthy or infected tissues of this plant. Our results suggest that, although conserved defence signals, such as SA and OPDA, are synthesized and are probably involved in the defence response of P. patens against B. cinerea infection, JA production appears to be missing. Interestingly, P. patens responds to OPDA and methyl jasmonate by reducing moss colony growth and rhizoid length, suggesting that jasmonate perception is present in mosses. Thus, P. patens can provide clues with regard to the evolution of different defence pathways in plants, including signalling and perception of OPDA and jasmonates in nonflowering and flowering plants. © 2012 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation.

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Franz, Marcus; Wolheim, Anke; Richter, Petra; Umbreit, Claudia; Dahse, Regine; Driemel, Oliver; Hyckel, Peter; Virtanen, Ismo; Kosmehl, Hartwig; Berndt, Alexander

2010-04-01

The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains alpha2, alpha3, alpha4, alpha5 and gamma2 in the stromal compartment/vascular structures in OSCC was analysed. Frozen tissue of OSCC (9x G1, 24x G2, 8x G3) and normal (2x)/hyperplastic (11x) oral mucosa was subjected to laminin chain and alpha-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Stromal laminin alpha2 chain significantly decreases and alpha3, alpha4, alpha5 and gamma2 chains and also ASMA significantly increase with rising grade. The amount of stromal alpha3, alpha4 and gamma2 chains significantly increased with rising ASMA positivity. There is a significant decrease in alpha3 chain positive vessels with neoplastic transformation. Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning alpha3 and gamma2 chain laminins during tumour angioneogenesis is suggested.

Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

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Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

2007-09-01

Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen

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Keyuan Liu

2017-11-01

Full Text Available Objective This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. Methods To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C. The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. Results The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05. The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05. The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. Conclusion This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter.

Dietary intake and food sources of fatty acids in Australian adolescents.

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O'Sullivan, Therese A; Ambrosini, Gina; Beilin, Lawrie J; Mori, Trevor A; Oddy, Wendy H

2011-02-01

Dietary fat consumed during childhood and adolescence may be related to the development of cardiovascular and other chronic diseases in adulthood; however, there is a lack of information on specific fatty acid intakes and food sources in these populations. Our study aimed to assess fatty acid intakes in Australian adolescents, compare intakes with national guidelines, and identify major food sources of fatty acids. Dietary intake was assessed using measured 3-d records in 822 adolescents aged 13-15 y participating in The Western Australian Pregnancy Cohort (Raine) Study, Australia. Mean daily total fat intakes were 90 ± 25 g for boys and 73 ± 20 g for girls, with saturated fat contributing 14% of total energy intake. Mean contribution to daily energy intake for linoleic, alpha-linolenic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids were 3.0%, 0.40%, 0.02%, 0.01%, and 0.04%, respectively, for boys, and 3.3%, 0.42%, 0.02%, 0.01%, and 0.05% for girls. To meet guidelines for chronic disease prevention, consumption of long-chain omega-3 fatty acids in this population may need to increase up to three-fold and the proportion of saturated fat decrease by one-third. Girls were more likely to achieve the guidelines. Major food sources were dairy products for total fat, saturated fat and alpha-linolenic acid, margarines for linoleic acid, and fish for long-chain omega-3 fatty acids. Results suggest that for this population, a higher dietary intake of long-chain omega-3 fatty acids, particularly for boys, and lower proportion of saturated fat is required to meet recommendations for prevention of chronic disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

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Lotta, Luca A.; Scott, Robert A.; Luan, Jian’an; Tillin, Therese; Stewart, Isobel D.; Perry, John R. B.; Karoly, Edward D.; Forouhi, Nita G.; Zierath, Juleen R.; Savage, David B.; Griffin, Julian L.; Hingorani, Aroon D.; Khaw, Kay-Tee; O’Rahilly, Stephen; Langenberg, Claudia

2016-01-01

Background Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Methods and Findings Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26–1.65, p = 9.5 × 10−8) for isoleucine, 1.85 (95% CI 1.41–2.42, p = 7.3 × 10−6) for leucine, and 1.54 (95% CI 1.28–1.84, p = 4.2 × 10−6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Conclusions Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the

Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

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Luca A Lotta

2016-11-01

Full Text Available Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question.Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8. The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25, encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8 for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6 for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6 for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are

Imaging Tumor Vasculature Noninvasively with Positron Emission Tomography and RGD Peptides Labeled with Copper 64 Using the Bifunctonal Chelates DOTA, Oxo-DO3A. and PCTA

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Donald T.T. Yapp

2013-06-01

Full Text Available Two novel bifunctional chelates, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15,11,13-triene-3,6,9-triacetic acid (PCTA and 1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (Oxo-DO3A, were found to radiolabel antibodies with copper 64 (64Cu well for positron emission tomography (PET. In this study, the same chelators were used to radiolabel peptides with 64Cu for PET imaging of angiogenesis. PCTA, Oxo-DO3A, and 1,4,7,10-tetraazacyclododecane-N,N‘,N“,N”’-tetraacetic acid (DOTA were conjugated to cyclic-(RGDyK, and their binding affinities were confirmed. Conditions for 64Cu radiolabeling were optimized for maximum yield and specific activity. The in vitro stability of the radiolabeled compounds was challenged with serum incubation. PET studies were carried out in a non-αvβ3-expressing tumor model to evaluate the compounds' specificity for proliferating tumor vasculature and their in vivo pharmacokinetics. The PCTA and Oxo-DO3A bioconjugates were labeled with 64Cu at higher effective specific activity and radiochemical yield than the DOTA bioconjugate. In the imaging studies, all the 64Cu bioconjugates could be used to visualize the tumor and the radiotracer uptake was blocked with cyclic-(RGDyK. Target uptake of each bioconjugate was similar, but differences in other tissues were observed. 64Cu-PCTA-RGD showed the best clearance from nontarget tissue and the highest tumor to nontarget ratios. PCTA was the most promising bifunctional chelate for 64Cu peptide imaging and warrants further investigation.

Effect of Supplementation of Branched Chain Fatty Acid on Colony of Ruminal Bacteria and Cell of Protozoa

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W Suryapratama

2009-05-01

Full Text Available A study was conducted to evaluate the potential of branched-chain volatile fatty acids (isobutyric, α-methylbutyric and β-methylbutiric that supplemented into the diet on the colony of ruminal bacteria and the cell of protozoa population. Five progeny Friesian Holstein males with initial weight 348±29 kg were used in a 5x5 Latin square design (30-d periods. The basal diet composed of 55% forage and 45% concentrate containing 10.5 MJ ME/kg and 15% crude protein (CP. There were five dietary treatments where A: basal diet, B: A+139 mg urea/kg W0.75, C: B+28 mg CaSO4/kg W0.75, D: C+0.05 mM isobutyric acid+0.05 mM β-methylbutyric acid, and E: D+0.05 mM α-methylbutyric acid. Rearing period was 30 days, consists of feed adaptation period 20 days, then growth observation was done within the last 10 days. Collection of ruminal fluid was done within the last day of observation period, and took 3-4 h after the feeding. The results showed that supplementation branched chain volatile fatty acids did not significant affect on the number of colonies of bacteria and protozoa population, but the significant effect (P<0.05 on the concentration of branched chain volatile fatty acids in the rumen fluid. The supplementation of α-methylbutyric (P <0.05 decreased of concentration of isobutyric and isovaleric in rumen fluid than the other treatments. It is concluded that supplementation of branched chain volatile fatty acids not used by rumen bacteria for their growth but for the elongation of fatty acid synthesis. The supplementation of branched chain volatile fatty acids was 0.05 mM not enough strong influence on the growth of colony of rumen bacteria. (Animal Production 11(2: 129-134 (2009 Key Words: rumen fermentation, branched-chain fatty acid, ruminal bacteria, protozoa

(E-3-Methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenylprop-1-en-1-yl-2(3H-benzothiazolone

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Yordanka Ivanova

2016-09-01

Full Text Available The title compound, (E-3-methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenylprop-1-en-1-yl-2(3H-benzothiazolone, was synthesized by both an acid- and base-catalyzed aldol condensation of 3-methyl-6-acetyl-2(3H-benzothiazolone and 3,4,5-trimethoxyacetophenone. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

Effects of medium-chain triglycerides, long-chain triglycerides, or 2-monododecanoin on fatty acid composition in the portal vein, intestinal lymph, and systemic circulation in rats.

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You, Yi-Qian Nancy; Ling, Pei-Ra; Qu, Jason Zhensheng; Bistrian, Bruce R

2008-01-01

Fatty acid absorption patterns can have a major impact on the fatty acid composition in the portal, intestinal lymph, and systemic circulation. This study sought to determine the effects of long-chain triglycerides (LCT), medium-chain triglycerides (MCT), and 2-monododecanoin (2mono) on intestinal fatty acid composition during continuous feeding over a brief period. The lipid sources were 100% LCT, 100% MCT, a 50:50 mixture of LCT and MCT (LCT/MCT), and a 50:50 mixture of LCT and 2mono (LCT/2mono). A total of 27 rats were randomly given 1 of the 4 diets at 200 kcal/kg/d, with 30% of total calories from lipids over 3 hours. MCT significantly increased each of the medium-chain fatty acids (C6:0, C8:0, and C10:0) as free fatty acids in the portal vein and about 10%/mol of C10:0 as triglycerides in the lymph compared with the other groups. There was significantly less C10:0 in lymphatic triglycerides with LCT/MCT than with MCT, but more than in the LCT and LCT/2mono diets. MCT also significantly increased the contents of C16:0, C18:0, C18:1, and C20:4 in the lymphatic triglycerides compared with all other groups including LCT/MCT. The amount of linoleic acid (C18:2) in lymphatic triglycerides followed the relative amounts of this fatty acid in the diet, with the greatest in LCT followed by LCT/MCT and LCT/2mono and least in MCT. A so-called structured lipid composed of the medium-chain fatty acid dodecanoic acid on the 2 position and long-chain fatty acids on the 1 and 3 positions appeared to be endogenously synthesized in response to the LCT/2mono diet. The original differences in MCT and LCT content in the diets were preserved in the fatty acid composition in the intestinal free fatty acids and triglycerides during feeding. In addition, the duration of lipid administration can play a role in altering fatty acid composition in the intestine.

Effects of Medium-Chain Triglycerides, Long-Chain Triglycerides, or 2-Monododecanoin on Fatty Acid Composition in the Portal Vein, Intestinal Lymph, and Systemic Circulation in Rats

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Nancy You, Yi-Qian; Ling, Pei-Ra; Qu, Jason Zhensheng; Bistrian, Bruce R.

2011-01-01

Background Fatty acid absorption patterns can have a major impact on the fatty acid composition in the portal, intestinal lymph, and systemic circulation. This study sought to determine the effects of long-chain triglycerides (LCT), medium-chain triglycerides (MCT), and 2-monododecanoin (2mono) on intestinal fatty acid composition during continuous feeding over a brief period. Methods The lipid sources were 100% LCT, 100% MCT, a 50:50 mixture of LCT and MCT (LCT/MCT), and a 50:50 mixture of LCT and 2mono (LCT/2mono). A total of 27 rats were randomly given 1 of the 4 diets at 200 kcal/kg/d, with 30% of total calories from lipids over 3 hours. Results MCT significantly increased each of the medium-chain fatty acids (C6:0, C8:0, and C10:0) as free fatty acids in the portal vein and about 10%/mol of C10:0 as triglycerides in the lymph compared with the other groups. There was significantly less C10:0 in lymphatic triglycerides with LCT/MCT than with MCT, but more than in the LCT and LCT/2mono diets. MCT also significantly increased the contents of C16:0, C18:0, C18:1, and C20:4 in the lymphatic triglycerides compared with all other groups including LCT/MCT. The amount of linoleic acid (C18:2) in lymphatic triglycerides followed the relative amounts of this fatty acid in the diet, with the greatest in LCT followed by LCT/MCT and LCT/2mono and least in MCT. A so-called structured lipid composed of the medium-chain fatty acid dodecanoic acid on the 2 position and long-chain fatty acids on the 1 and 3 positions appeared to be endogenously synthesized in response to the LCT/2mono diet. Conclusions The original differences in MCT and LCT content in the diets were preserved in the fatty acid composition in the intestinal free fatty acids and triglycerides during feeding. In addition, the duration of lipid administration can play a role in altering fatty acid composition in the intestine. PMID:18407910

Branched-chain amino acids in metabolic signaling and insulin resistance

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Branched-chain amino acids (BCAAs) are important directly- and indirectly-acting nutrient signals. Frequently, their actions have been reported to be anti-obesity in nature, especially in rodent models. Yet, circulating BCAAs tend to be elevated in obesity, and even associated with poorer metaboli...

Abiotic and biotic degradation of oxo-biodegradable plastic bags by Pleurotus ostreatus.

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José Maria Rodrigues da Luz

Full Text Available In this study, we evaluated the growth of Pleurotus ostreatus PLO6 using oxo-biodegradable plastics as a carbon and energy source. Oxo-biodegradable polymers contain pro-oxidants that accelerate their physical and biological degradation. These polymers were developed to decrease the accumulation of plastic waste in landfills. To study the degradation of the plastic polymers, oxo-biodegradable plastic bags were exposed to sunlight for up to 120 days, and fragments of these bags were used as substrates for P. ostreatus. We observed that physical treatment alone was not sufficient to initiate degradation. Instead, mechanical modifications and reduced titanium oxide (TiO2 concentrations caused by sunlight exposure triggered microbial degradation. The low specificity of lignocellulolytic enzymes and presence of endomycotic nitrogen-fixing microorganisms were also contributing factors in this process.

Abiotic and biotic degradation of oxo-biodegradable plastic bags by Pleurotus ostreatus.

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da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Bazzolli, Denise Mara Soares; Tótola, Marcos Rogério; Demuner, Antônio Jacinto; Kasuya, Maria Catarina Megumi

2014-01-01

In this study, we evaluated the growth of Pleurotus ostreatus PLO6 using oxo-biodegradable plastics as a carbon and energy source. Oxo-biodegradable polymers contain pro-oxidants that accelerate their physical and biological degradation. These polymers were developed to decrease the accumulation of plastic waste in landfills. To study the degradation of the plastic polymers, oxo-biodegradable plastic bags were exposed to sunlight for up to 120 days, and fragments of these bags were used as substrates for P. ostreatus. We observed that physical treatment alone was not sufficient to initiate degradation. Instead, mechanical modifications and reduced titanium oxide (TiO2) concentrations caused by sunlight exposure triggered microbial degradation. The low specificity of lignocellulolytic enzymes and presence of endomycotic nitrogen-fixing microorganisms were also contributing factors in this process.

Abiotic and Biotic Degradation of Oxo-Biodegradable Plastic Bags by Pleurotus ostreatus

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da Luz, José Maria Rodrigues; Paes, Sirlaine Albino; Bazzolli, Denise Mara Soares; Tótola, Marcos Rogério; Demuner, Antônio Jacinto; Kasuya, Maria Catarina Megumi

2014-01-01

In this study, we evaluated the growth of Pleurotus ostreatus PLO6 using oxo-biodegradable plastics as a carbon and energy source. Oxo-biodegradable polymers contain pro-oxidants that accelerate their physical and biological degradation. These polymers were developed to decrease the accumulation of plastic waste in landfills. To study the degradation of the plastic polymers, oxo-biodegradable plastic bags were exposed to sunlight for up to 120 days, and fragments of these bags were used as substrates for P. ostreatus. We observed that physical treatment alone was not sufficient to initiate degradation. Instead, mechanical modifications and reduced titanium oxide (TiO2) concentrations caused by sunlight exposure triggered microbial degradation. The low specificity of lignocellulolytic enzymes and presence of endomycotic nitrogen-fixing microorganisms were also contributing factors in this process. PMID:25419675

Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes.

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Klette, K L; Anderson, C J; Poch, G K; Nimrod, A C; ElSohly, M A

2000-10-01

The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

Significance of long chain polyunsaturated fatty acids in human health

Czech Academy of Sciences Publication Activity Database

Zárate, R.; El Jaber-Vazdekis, Nabil; Tejera, N.; Pérez, J.A.; Rodrígues, C.

2017-01-01

Roč. 6, JUL 27 (2017), s. 1-19, č. článku 25. ISSN 2001-1326 R&D Projects: GA MŠk(CZ) LO1416 Institutional support: RVO:61388971 Keywords : Lipidomics * Lipids * Long chain polyunsaturated fatty acids Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology

Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

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Oliver, A. E.; Deamer, D. W.

1994-01-01

Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

Induction of peroxisomal beta-oxidation by a microbial catabolite of cholic acid in rat liver and cultured rat hepatocytes.

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Nishimaki-Mogami, T; Takahashi, A; Toyoda, K; Hayashi, Y

1993-01-01

The capability of (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo-1H-cyclopental[f]quinolin-7 beta-yl)valeric acid (DCQVA), a catabolite of cholic acid produced by enterobacteria, to induce peroxisome proliferation in vivo and in vitro was studied. Rats given 0.3% DCQVA in the diet for 2 weeks showed marked increases in peroxisomal beta-oxidation, mitochondrial 2,4-dienoyl-CoA reductase and microsomal laurate omega-oxidation activities in the liver compared with control rats given the diet without DCQVA. Cultured rat hepatocytes treated with DCQVA for 72 h also exhibited greatly enhanced beta-oxidation activity. The increased activity was concentration-dependent and the effective concentrations were comparable with those of clofibric acid that produced the same degree of induction in the assay. The results demonstrate that DCQVA is a potent peroxisome proliferator that occurs naturally in rat intestine. PMID:8216219

Thermometric titration of beta-aryl-alpha-mercaptopropenoic acids and determination of the stoichiometry of their metal complexes.

Science.gov (United States)

Izquierdo, A; Carrasco, J

1981-05-01

Automatic thermometric titration was applied to some beta-aryl-alpha-mercaptopropenoic acids and the stoichiometry of their complexes with several metal ions was investigated. The heats of neutralization of the mercapto-acids with sodium hydroxide and the heats of their reaction with metal ions were calculated.

Distinct energetics and closing pathways for DNA polymerase β with 8-oxoG template and different incoming nucleotides

Directory of Open Access Journals (Sweden)

Wang Yanli

2007-02-01

Full Text Available Abstract Background 8-Oxoguanine (8-oxoG is a common oxidative lesion frequently encountered by DNA polymerases such as the repair enzyme DNA polymerase β (pol β. To interpret in atomic and energetic detail how pol β processes 8-oxoG, we apply transition path sampling to delineate closing pathways of pol β 8-oxoG complexes with dCTP and dATP incoming nucleotides and compare the results to those of the nonlesioned G:dCTP and G:dATPanalogues. Results Our analyses show that the closing pathways of the 8-oxoG complexes are different from one another and from the nonlesioned analogues in terms of the individual transition states along each pathway, associated energies, and the stability of each pathway's closed state relative to the corresponding open state. In particular, the closed-to-open state stability difference in each system establishes a hierarchy of stability (from high to low as G:C > 8-oxoG:C > 8-oxoG:A > G:A, corresponding to -3, -2, 2, 9 kBT, respectively. This hierarchy of closed state stability parallels the experimentally observed processing efficiencies for the four pairs. Network models based on the calculated rate constants in each pathway indicate that the closed species are more populated than the open species for 8-oxoG:dCTP, whereas the opposite is true for 8-oxoG:dATP. Conclusion These results suggest that the lower insertion efficiency (larger Km for dATP compared to dCTP opposite 8-oxoG is caused by a less stable closed-form of pol β, destabilized by unfavorable interactions between Tyr271 and the mispair. This stability of the closed vs. open form can also explain the higher insertion efficiency for 8-oxoG:dATP compared to the nonlesioned G:dATP pair, which also has a higher overall conformational barrier. Our study offers atomic details of the complexes at different states, in addition to helping interpret the different insertion efficiencies of dATP and dCTP opposite 8-oxoG and G.

Gut microbiota–derived short-chain fatty acids and kidney diseases

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Li L

2017-12-01

Full Text Available Lingzhi Li, Liang Ma, Ping Fu Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China Abstract: Gut microbiota and its metabolites play pivotal roles in host physiology and pathology. Short-chain fatty acids (SCFAs, as a group of metabolites, exert positive regulatory effects on energy metabolism, hormone secretion, immune inflammation, hypertension, and cancer. The functions of SCFAs are related to their activation of transmembrane G protein-coupled receptors and their inhibition of histone acetylation. Though controversial, growing evidence suggests that SCFAs, which regulate inflammation, oxidative stress, and fibrosis, have been involved in kidney disease through the activation of the gut–kidney axis; however, the molecular relationship among gut microbiota–derived metabolites, signaling pathways, and kidney disease remains to be elucidated. This review will provide an overview of the physiology and functions of SCFAs in kidney disease. Keywords: gut microbiome, short-chain fatty acids, kidney diseases, gut–kidney axis

Lipase-catalyzed esterification of lactic acid with straight-chain alcohols

DEFF Research Database (Denmark)

Rønne, Torben Harald; Xu, Xuebing; Tan, Tianwei

2005-01-01

Enzymatic synthesis of esters of lactic acid and straight-chain alcohols with different chain lengths (C6–C18) were investigated in batch reactions with hexadecanol (C16) as the model alcohol. Cyclohexane was the best solvent for higher ester yields, and the best biocatalyst was the immobilized...... Candida antarctica lipase B (Novozym 435) as well as the textile-immobilized Candida sp. lipase. A method was established to obtain ester yields in the range of 71 to 82% for the different alcohols, and the most favorable conditions for the esterification reaction using Novozym 435 were an equimolar ratio...... of lactic acid to alcohol, each at a concentration of 120 mM each; a 50°C reaction temperature; 190 rpm shaking speed; and the addition of 100 mg molecular sieves (4 Å) for drying. The ester yield increased with increasing lipase load, and a yield of 79.2% could be obtained after 24 h of reaction at 20 wt...

Serum alpha-tocopherol and ascorbic acid concentrations in Type 1 and Type 2 diabetic patients with and without angiopathy.

Science.gov (United States)

Skrha, Jan; Prázný, Martin; Hilgertová, Jirina; Weiserová, Hana

2003-03-01

Alpha-tocopherol and ascorbic acid form a part of scavenger system influencing the level of oxidative stress in diabetes mellitus. The aim of this study was to evaluate serum concentrations of alpha-tocopherol and ascorbic acid in Type 1 and Type 2 diabetes mellitus and to compare them with the presence of vascular complications as well as with oxidative stress and endothelial dysfunction. A total of 38 Type 1 and 62 Type 2 diabetic patients were subdivided into those with and without angiopathy. Serum alpha-tocopherol and ascorbic acid concentrations were estimated in all patients and in 38 healthy persons. Their results were compared with diabetes control, with oxidative stress measured by plasma malondialdehyde and with endothelial dysfunction estimated by serum N-acetyl-beta-glucosaminidase activity. In addition, the differences in biochemical variables were compared between patients with and without angiopathy. Serum alpha-tocopherol related to the sum of cholesterol and triglyceride concentrations (AT/CHT ratio) was significantly lower in diabetic patients with macroangiopathy than in those without vascular changes (pascorbic acid levels were significantly lower only in Type 2 diabetic patients with macroangiopathy as compared with healthy controls as well as with patients without vascular disease (pcholesterol or triglyceride concentrations in both Type 1 and Type 2 diabetic patients. The presence of oxidative stress together with endothelial dysfunction measured by N-acetyl-beta-glucosaminidase activity was accompanied by lower AT/CHT ratio (pascorbic acid concentration in serum. Their low concentrations may participate at the increased level of oxidative stress in these individuals.

Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle.

Science.gov (United States)

Cohn, R D; Mayer, U; Saher, G; Herrmann, R; van der Flier, A; Sonnenberg, A; Sorokin, L; Voit, T

1999-03-01

The integrins are a large family of heterodimeric transmembrane cellular receptors which mediate the association between the extracellular matrix (ECM) and cytoskeletal proteins. The alpha7beta1 integrin is a major laminin binding integrin in skeletal and cardiac muscle and is thought to be involved in myogenic differentiation and migration processes. The main binding partners of the alpha7 integrin are laminin-1 (alpha1-beta1-gamma1), laminin-2 (alpha2-beta1-gamma1) and laminin-4 (alpha2-beta2-gamma1). Targeted deletion of the gene for the alpha7 integrin subunit (ITGA7) in mice leads to a novel form of muscular dystrophy. In the present study we have investigated the expression of two alternative splice variants, the alpha7B and beta1D integrin subunits, in normal human skeletal muscle, as well as in various forms of muscular dystrophy. In normal human skeletal muscle the expression of the alpha7 integrin subunit appeared to be developmentally regulated: it was first detected at 2 years of age. In contrast, the beta1D integrin could be detected in immature and mature muscle in the sarcolemma of normal fetal skeletal muscle at 18 weeks gestation. The expression of alpha7B integrin was significantly reduced at the sarcolemma in six patients with laminin alpha2 chain deficient congenital muscular dystrophy (CMD) (age >2 years). However, this reduction was not correlated with the amount of laminin alpha2 chain expressed. In contrast, the expression of the laminin alpha2 chain was not altered in the skeletal muscle of the alpha7 knock-out mice. These data argue in favor that there is not a tight correlation between the expression of the alpha7 integrin subunit and that of the laminin alpha2 chain in either human or murine dystrophic muscle. Interestingly, in dystrophinopathies (Duchenne and Becker muscular dystrophy; DMD/BMD) expression of alpha7B was upregulated irrespective of the level of dystrophin expression as shown by a strong sarcolemmal staining pattern even