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Acid Synthesis (acid + synthesis)
Kinds of Acid Synthesis Selected AbstractsOrtholithiation of Unprotected Benzoic Acids: Application for Novel 2-Chloro-6-substituted Benzoic Acid Syntheses.CHEMINFORM, Issue 33 2005Frederic Gohier Abstract For Abstract see ChemInform Abstract in Full Text. [source] Effect of Salt Stress on the Salicylic Acid Synthesis in Young Maize (Zea mays L.) PlantsJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 3 2009G. Szalai Abstract The effect of salt stress on salicylic acid (SA) synthesis was investigated parallel with the induction of antioxidant enzymes in young maize plants. Two-week-old maize plants grown in hydroponic solution were treated with 50 or 100 mm NaCl for 7 days. Antioxidant enzyme activities, and the SA and o -hydroxy-cinnamic acid (oHCA) levels were measured on the 3rd and 7th day of treatment and after 4 days of recovery. Ascorbate peroxidase activity increased in the leaves, but changes in guaiacol peroxidase activity only could be detected in the roots after 7 days. Glutathione reductase activity increased both in the leaves and in the roots after the 3rd day of 100 mm NaCl treatment. Free SA only increased during recovery in the leaves and roots. In the leaves of plants treated with 100 mm NaCl, a slight increase was observed in the free oHCA level, which rose dramatically after recovery, while in the roots an increase could only be seen after recovery. These results suggest that oHCA may serve not only as a precursor of SA but may also have an antioxidant role during salt stress and recovery. [source] Antioxidant Protection Mechanisms And Arachidonic Acid Synthesis Are Altered In Schwann Cells Grown In Elevated GlucoseJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000C Miinea Accumulating evidence points to oxidative stress as an important factor in the onset of diabetic neuropathy. We have investigated the status of antioxidant protection mechanisms in immortalized rat Schwann cells cultured in high (30 and 50 mM) concentrations of glucose. As compared to growth in 5 mM glucose, the cells contained 40% less reduced glutathione (n =8, p < 0.01). Total superoxide dismutase activity was diminished by more than 50% (n=3; p < 0.001), whereas catalase activity was unchanged. The cellular NADH/NAD+ ratio was progressively increased with increasing medium glucose concentrations. Our previous findings have established that upon exposure of cultured cells to elevated glucose, the proportions of arachidonic acid-containing molecular species (ACMS) in phospholipids are decreased in a pattern similar to alterations exhibited by diabetic nerve. To examine whether biosynthesis of arachidonic acid might be perturbed, confluent cells maintained in either high or low glucose were incubated with either [14C]linoleic acid (18:2) or [14C]dihomo-,-linolenic acid (20:3) and radioactivity incorporated into molecular species of major phospholipid classes was measured. The incorporation of 18:2 either as unchanged fatty acid or into ACMS did not differ as a function of glucose concentration. Negligible labeled 18:3 or 20:3 molecular species were detected. In contrast, the uptake of 20:3 into 18:1/20:4 and 16:0/20:4 phosphatidylcholine and 18:1/20:4 phosphatidylethanolamine, but not into 20:3-containing molecular species, was significantly reduced in cells cultured in 30 mM glucose. These data imply that ,5 desaturase activity is decreased in cells exposed to elevated glucose. This reduced enzyme activity could adversely affect polyunsaturated fatty acid metabolism and might arise as a consequence of impaired scavenging of reactive oxygen species. (Supported by NIH grant DK30577) [source] Free Radical-Mediated Aryl Amination and Its Use in a Convergent [3 + 2] Strategy for Enantioselective Indoline ,-Amino Acid Synthesis.CHEMINFORM, Issue 22 2003Rajesh Viswanathan Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Scope and Limitations in the Use of N-(PhF)Serine-Derived Cyclic Sulfamidates for Amino Acid Synthesis.CHEMINFORM, Issue 41 2001Lan Wei Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instabilityAPMIS, Issue 5 2010SANG YONG SONG Song SY, Kang MR, Yoo NJ, Lee SH. Mutational analysis of mononucleotide repeats in dual specificity tyrosine phosphatase genes in gastric and colon carcinomas with microsatellite instability. APMIS 2010; 118: 389,93. Coordinated protein phosphorylation and dephosphorylation are crucial in the regulation of cell signaling, and disruption of the coordination is known to play important roles in cancer development. Recent reports revealed that classical protein tyrosine phosphatase (PTP)-encoded genes are somatically mutated in human colorectal cancer. However, data on dual specificity phosphatase (DPTP) gene mutations in human cancers are lacking. By analyzing a public genomic database, we found that five DPTP genes, CDC14A, MTM1, MTMR3, SSH1, and SSH2, have mononucleotide repeats in their coding DNA sequences. To see whether these genes are mutated in cancers with microsatellite instability (MSI), we analyzed the mononucleotide repeats in 26 gastric cancers (GC) with MSI (MSI-H), 12 GC with low MSI (MSI-L), 45 GC with stable MSI (MSS), 33 colorectal cancers (CRC) with MSI-H, 14 CRC with MSI-L, and 45 CRC with MSS by single-strand conformation polymorphism (SSCP). We found CDC14A and MTMR3 mutations in five and one cancer (s), respectively. These mutations were detected in MSI-H cancers, but not in MSI-L or MSS cancers. The GC and CRC with MSI-H harbored the mutations in 15% and 6%, respectively. The CDC14A and MTMR3 mutations detected in the GC and CRC were deletion or duplication mutations of one base in the nucleotide repeats that would result in premature stops of the amino acid syntheses. Our data show that frameshift mutations of DPTP genes in MSI-H cancers occur at moderate frequencies. The data suggested that alterations in the CDC14A and MTMR3 genes may play a role in the development of GC and CRC with MSI-H by deregulating phosphatase functions possibly together with mutations of classical PTP genes. [source] Novel pathways for glycaemic control in type 2 diabetes: focus on bile acid modulationDIABETES OBESITY & METABOLISM, Issue 11 2008Eliot A. Brinton Type 2 diabetes is a common disorder with high risk of macrovascular and microvascular complications. These complications are largely driven by hyperglycaemia, dyslipidaemia and hypertension, for which aggressive treatment is thus warranted. Achieving and maintaining control of all three risk factors is especially difficult, however, and new therapeutic approaches could be useful. Bile acids have a well-established and important role in cholesterol homeostasis. Normally, their levels are maintained primarily by ileal reabsorption and enterohepatic recycling. Bile acid sequestrants bind bile acids in the intestine, reduce this recycling and deplete the bile acid pool, thereby stimulating use of hepatic cholesterol for bile acid synthesis, which leads to accelerated removal of LDL from the plasma and a decrease in LDL-cholesterol levels. Interestingly, recent evidence suggests that bile acid sequestrants can lower glucose levels to a clinically meaningful degree. This review presents this evidence and the possible mechanisms by which these glucose-lowering effects occur and discusses the apparently unique ability of bile acid sequestrants among lipid-lowering agents to significantly improve two cardiovascular risk factors, hyperglycaemia and dyslipidaemia. There is renewed interest in the use of bile acid sequestrants in individuals with type 2 diabetes, most of whom would benefit from additional reductions in both LDL-cholesterol and glycaemia. [source] Growth-induced changes in the proteome of Helicobacter pyloriELECTROPHORESIS, Issue 5-6 2006Christina Uwins Abstract Helicobacter pylori is a major human pathogen that is responsible for a number of gastrointestinal infections. We have used 2-DE to characterise protein synthesis in bacteria grown either on solid agar-based media or in each of two broth culture media (Brucella and brain heart infusion (BHI) broth). Significant differences were observed in the proteomes of bacteria grown either on agar-based or in broth media. Major changes in protein abundance were identified using principal component analysis (PCA), which delineated the profiles derived for the three key growth conditions (i.e. agar plates, Brucella and BHI broth). Proteins detected across the gel series were identified by peptide mass mapping and Edman sequencing. A number of proteins associated with protein synthesis in general as well as specific amino acid synthesis were depressed in broth-grown bacteria compared to plate-grown bacteria. A similar reduction was also observed in the abundance of proteins involved in detoxification. Two of the most abundant spots, identified as UreB and GroEL, in plate-grown bacteria showed a >140-fold drop in abundance in bacteria grown in Brucella broth compared to bacteria grown on agar plates. Two protein spots induced in bacteria grown in broth culture were both identified as glyceraldehyde 3-phosphate dehydrogenase based on their N -terminal amino acid sequences derived by Edman degradation. The underlying causes of the changes in the proteins abundance were not clear, but it was likely that a significant proportion of the changes were due to the alkaline pH of the broth culture media. [source] Sodium lauryl sulphate alters the mRNA expression of lipid-metabolizing enzymes and PPAR signalling in normal human skin in vivoEXPERIMENTAL DERMATOLOGY, Issue 12 2009Hans Törmä Abstract:, Detergents irritate skin and affect skin barrier homeostasis. In this study, healthy skin was exposed to 1% sodium lauryl sulphate (SLS) in water for 24 h. Biopsies were taken 6 h to 8 days post exposure. Lipid patterns were stained in situ and real-time polymerase chain reaction (PCR) was used to examine mRNA expression of enzymes synthesizing barrier lipids, peroxisome proliferator-activated receptors (PPAR) and lipoxygenases. The lipid pattern was disorganized from 6 h to 3 days after SLS exposure. Concomitant changes in mRNA expression included: (i) reduction, followed by induction, of ceramide-generating ,-glucocerebrosidase, (ii) increase on day 1 of two other enzymes for ceramide biosynthesis and (iii) persistent reduction of acetyl-CoA carboxylase-B, a key enzyme in fatty acid synthesis. Surprisingly, the rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase, was unaltered. Among putative regulators of barrier lipids synthesis, PPAR, and PPAR, exhibited reduced mRNA expression, while PPAR,/, and LXR, were unaltered. Epidermal lipoxygenase-3, which may generate PPAR, agonists, exhibited reduced expression. In conclusion, SLS induces reorganization of lipids in the stratum corneum, which play a role in detergents' destruction of the barrier. The changes in mRNA expression of enzymes involved in synthesizing barrier lipids are probably important for the restoration of the barrier. [source] Implication of the glutamine synthetase/glutamate synthase pathway in conditioning the amino acid metabolism in bundle sheath and mesophyll cells of maize leavesFEBS JOURNAL, Issue 12 2008Marie-Hélène Valadier We investigated the role of glutamine synthetases (cytosolic GS1 and chloroplast GS2) and glutamate synthases (ferredoxin-GOGAT and NADH-GOGAT) in the inorganic nitrogen assimilation and reassimilation into amino acids between bundle sheath cells and mesophyll cells for the remobilization of amino acids during the early phase of grain filling in Zea mays L. The plants responded to a light/dark cycle at the level of nitrate, ammonium and amino acids in the second leaf, upward from the primary ear, which acted as the source organ. The assimilation of ammonium issued from distinct pathways and amino acid synthesis were evaluated from the diurnal rhythms of the transcripts and the encoded enzyme activities of nitrate reductase, nitrite reductase, GS1, GS2, ferredoxin-GOGAT, NADH-GOGAT, NADH-glutamate dehydrogenase and asparagine synthetase. We discerned the specific role of the isoproteins of ferredoxin and ferredoxin:NADP+ oxidoreductase in providing ferredoxin-GOGAT with photoreduced or enzymatically reduced ferredoxin as the electron donor. The spatial distribution of ferredoxin-GOGAT supported its role in the nitrogen (re)assimilation and reallocation in bundle sheath cells and mesophyll cells of the source leaf. The diurnal nitrogen recycling within the plants took place via the specific amino acids in the phloem and xylem exudates. Taken together, we conclude that the GS1/ferredoxin-GOGAT cycle is the main pathway of inorganic nitrogen assimilation and recycling into glutamine and glutamate, and preconditions amino acid interconversion and remobilization. [source] The specificity of alcohol dehydrogenase with cis -retinoidsFEBS JOURNAL, Issue 9 2004Activity with 11- cis -retinol, localization in retina Studies in knockout mice support the involvement of alcohol dehydrogenases ADH1 and ADH4 in retinoid metabolism, although kinetics with retinoids are not known for the mouse enzymes. Moreover, a role of alcohol dehydrogenase (ADH) in the eye retinoid interconversions cannot be ascertained due to the lack of information on the kinetics with 11- cis -retinoids. We report here the kinetics of human ADH1B1, ADH1B2, ADH4, and mouse ADH1 and ADH4 with all- trans -, 7- cis -, 9- cis -, 11- cis - and 13- cis -isomers of retinol and retinal. These retinoids are substrates for all enzymes tested, except the 13- cis isomers which are not used by ADH1. In general, human and mouse ADH4 exhibit similar activity, higher than that of ADH1, while mouse ADH1 is more efficient than the homologous human enzymes. All tested ADHs use 11- cis -retinoids efficiently. ADH4 shows much higher kcat/Km values for 11- cis -retinol oxidation than for 11- cis -retinal reduction, a unique property among mammalian ADHs for any alcohol/aldehyde substrate pair. Docking simulations and the kinetic properties of the human ADH4 M141L mutant demonstrated that residue 141, in the middle region of the active site, is essential for such ADH4 specificity. The distinct kinetics of ADH4 with 11- cis -retinol, its wide specificity with retinol isomers and its immunolocalization in several retinal cell layers, including pigment epithelium, support a role of this enzyme in the various retinol oxidations that occur in the retina. Cytosolic ADH4 activity may complement the isomer-specific microsomal enzymes involved in photopigment regeneration and retinoic acid synthesis. [source] Stereoselective biosynthesis of chloroarylpropane diols by the basidiomycete Bjerkandera adusta: exploring the roles of amino acids, pyruvate, glycerol and phenyl acetyl carbinolFEMS MICROBIOLOGY LETTERS, Issue 1 2003Peter James Silk Abstract Bjerkandera adusta produces many chlorometabolites including chlorinated anisyl metabolites (CAMs) and 1-arylpropane-1,2-diols (1, 2, 3, 4) as idiophasic metabolic products of l -phenylalanine. These diols are stereoselectively biosynthesized from a C7 -unit (benzylic, from l -phenylalanine) and a C2 -unit, of unknown origin, as predominantly erythro (1R,2S) enantiomers. Of the labeled amino acids tested as possible C2 -units, at the 4,10 mM level, none were found to efficiently label the 2,3-propane carbons of the diols. However, glycine (2- 13C), l -serine (2,3,3-d3) and l -methionine (methyl-d3) entered the biomethylation pathway. Neither pyruvate (2,3- 13C2), acetate (1,2- 13C2), acetaldehyde (d4) nor ethanol (ethyl-d5) labeled the 2,3-propane carbons of the diols at the 4,10 mM level. Pyruvate (2,3- 13C2) and l -serine (2,3,3-d3) (which also entered the biomethylation pathway) did, however, effectively label the 2,3-propane carbons of the ,-ketols and diols at the 40 mM level as evidenced by mass spectrometry. Glycerol (1,1,2,3,3-d5) also appeared to label one of the 2,3-propane carbons (ca. 5% as 2H2 in the C3 side chain) as suggested by mass spectrometric data and also entered the biomethylation pathway, likely via amino acid synthesis. Glycerol (through pyruvate), therefore, likely supplies C2 and C3 of the propane side chain with arylpropane diol biosynthesis. Incubation of B. adusta with synthetic [2- 2H1,2- 18O]-glycerol showed that neither 2H nor 18O were incorporated in the ,-ketols or diols. The oxygen atom on the C2 of the ketols/diols, therefore, does not appear to come from the oxygen atom on the C2 of glycerol. Glycerol, however, can readily form l -serine (which can then form pyruvate via PLP/serine dehydratase and involve transamination washing out the 18O label and providing the oxygen from water), and can then go on to label the C2 -unit. Labeled ,-ketol, phenyl acetyl carbinol (5) (PAC; ring-d5, 2,3- 13C2 propane) cultured with B. adusta leads to stereospecific reduction to the (1R,2S)-diol (6) (ring-d5 and 2,3- 13C2); in all other metabolites produced, the 2,3- 13C2 label is washed out. Incubation of the fungus with 4-fluorobenzaldehyde (13) produces a pooling of predominantly erythro (1R,2S) 1-(4,-fluorophenyl)-1,2-propane diol (18 as diacetate) (through the corresponding ,-ketols 16, 17). Blocking the para-position with fluorine thus appears to prevent ring oxygenation and also chlorination, forcing the conclusion that para-ring oxygenation precedes meta-chlorination. [source] Apparent growth phase-dependent phosphorylation of malonyl coenzyme A:acyl carrier protein transacylase (MCAT), a major fatty acid synthase II component in Mycobacterium bovis BCGFEMS MICROBIOLOGY LETTERS, Issue 1 2003Indrajit Sinha Abstract Probing protein extracts from exponentially growing and stationary phase cultures of Mycobacterium bovis BCG with anti-phospho amino acid antibodies revealed a 31-kDa anti-phospho threonine antibody-reactive protein specific to growing culture. The corresponding protein was purified via two-dimensional gel electrophoresis and identified via mass spectrometry to be malonyl coenzyme A:acyl carrier protein transacylase (MCAT), a component of the fatty acid biosynthetic pathway. MCAT tagged with histidine reacted with anti-phospho threonine antibody and was positive in an in-gel chemical assay for phospho proteins. Analysis of the growth phase dependence of MCAT-His phosphorylation and protein levels showed that phosphorylated MCAT-His can be detected only in growing culture. In contrast, MCAT-His protein level was growth phase-independent. These results suggest that MCAT may be a substrate of a protein kinase and phosphatase, and that aspects of fatty acid synthesis in tubercle bacilli are regulated by protein phosphorylation. [source] Nucleoside transporter expression and function in cultured mouse astrocytesGLIA, Issue 1 2005Liang Peng Abstract Uptake of purine and pyrimidine nucleosides in astrocytes is important for several reasons: (1) uptake of nucleosides contributes to nucleic acid synthesis; (2) astrocytes synthesize AMP, ADP, and ATP from adenosine and GTP from guanosine; and (3) adenosine and guanosine function as neuromodulators, whose effects are partly terminated by cellular uptake. It has previously been shown that adenosine is rapidly accumulated by active uptake in astrocytes (Hertz and Matz, Neurochem Res 14:755,760, 1989), but the ratio between active uptake and metabolism-driven uptake of adenosine is unknown, as are uptake characteristics for guanosine. The present study therefore aims at providing detailed information of nucleoside transport and transporters in primary cultures of mouse astrocytes. Reverse transcription-polymerase chain reaction identified the two equilibrative nucleoside transporters, ENT1 and ENT2, together with the concentrative nucleoside transporter CNT2, whereas CNT3 was absent, and CNT1 expression could not be investigated. Uptake studies of tritiated thymidine, formycin B, guanosine, and adenosine (3-s uptakes at 1,4°C to study diffusional uptake and 1,60-min uptakes at 37°C to study concentrative uptake) demonstrated a fast diffusional uptake of all four nucleosides, a small, Na+ -independent and probably metabolism-driven uptake of thymidine (consistent with DNA synthesis), larger metabolism-driven uptakes of guanosine (consistent with synthesis of DNA, RNA, and GTP) and especially of adenosine (consistent with rapid nucleotide synthesis), and Na+ -dependent uptakes of adenosine (consistent with its concentrative uptake) and guanosine, rendering neuromodulator uptake independent of nucleoside metabolism. Astrocytes are accordingly well suited for both intense nucleoside metabolism and metabolism-independent uptake to terminate neuromodulator effects of adenosine and guanosine. © 2005 Wiley-Liss, Inc. [source] Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice,HEPATOLOGY, Issue 5 2009Nora Bijl Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. The hyperinsulinemia that occurs as a consequence of insulin resistance is thought to be an important contributor to the development of fatty liver. We have shown that the iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase, is a potent enhancer of insulin signaling in rodent models for insulin resistance and type 2 diabetes. The present study was designed to assess the impact of AMP-DNM on insulin levels, liver triglyceride synthesis, and gene expression profile. Treatment of ob/ob mice with AMP-DNM restored insulin signaling in the liver, corrected blood glucose values to levels found in lean mice, and decreased insulin concentration. The expression of sterol regulatory element-binding protein 1c target genes involved in fatty acid synthesis normalized. AMP-DNM treatment significantly reduced liver to body weight ratio and reversed hepatic steatosis, comprising fat as well as inflammatory markers. In addition, AMP-DNM treatment corrected to a large extent the gene expression profile of ob/ob mice livers toward the profile of lean mice. Conclusion: Pharmacological lowering of glycosphingolipids with the iminosugar AMP-DNM is a promising approach to restore insulin signaling and improve glucose homeostasis as well as hepatic steatosis. (HEPATOLOGY 2009.) [source] Specific role for acyl CoA:Diacylglycerol acyltransferase 1 (Dgat1) in hepatic steatosis due to exogenous fatty acids,HEPATOLOGY, Issue 2 2009Claudio J. Villanueva Nonalcoholic fatty liver disease, characterized by the accumulation of triacylglycerols (TGs) and other lipids in the liver, often accompanies obesity and is a risk factor for nonalcoholic steatohepatitis and fibrosis. To treat or prevent fatty liver, a thorough understanding of hepatic fatty acid and TG metabolism is crucial. To investigate the role of acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), a key enzyme of TG synthesis, in fatty liver development, we studied mice with global and liver-specific knockout of Dgat1. DGAT1 was required for hepatic steatosis induced by a high-fat diet and prolonged fasting, which are both characterized by delivery of exogenous fatty acids to the liver. Studies in primary hepatocytes showed that DGAT1 deficiency protected against hepatic steatosis by reducing synthesis and increasing the oxidation of fatty acids. In contrast, lipodystrophy (aP2-SREBP-1c436) and liver X receptor activation (T0901317), which increase de novo fatty acid synthesis in liver, caused steatosis independently of DGAT1. Pharmacologic inhibition of Dgat1 with antisense oligonucleotides protected against fatty liver induced by a high-fat diet. Conclusion: Our findings identify a specific role for hepatic DGAT1 in esterification of exogenous fatty acids and indicate that DGAT1 contributes to hepatic steatosis induced by this mechanism. (HEPATOLOGY 2009.) [source] ,Klotho: A new kid on the bile acid biosynthesis block,HEPATOLOGY, Issue 1 2006Marco Arrese We have generated a line of mutant mouse that lacks ,Klotho, a protein that structurally resembles Klotho. The synthesis and excretion of bile acids were found to be dramatically elevated in these mutants, and the expression of 2 key bile acid synthase genes, cholesterol 7,-hydroxylase (Cyp7a1) and sterol 12,- hydroxylase (Cyp8b1), was strongly upregulated. Nuclear receptor pathways and the enterohepatic circulation, which regulates bile acid synthesis, seemed to be largely intact; however, bile acid,dependent induction of the small heterodimer partner (SHP) NR0B2, a common negative regulator of Cyp7a1 and Cyp8b1, was significantly attenuated. The expression of Cyp7a1 and Cyp8b1 is known to be repressed by dietary bile acids via both SHP-dependent and -independent regulations. Interestingly, the suppression of Cyp7a1 expression by dietary bile acids was impaired, whereas that of Cyp8b1 expression was not substantially altered in ,klotho,/, mice. Therefore, ,Klotho may stand as a novel contributor to Cyp7a1 -selective regulation. Additionally, ,Klotho-knockout mice exhibit resistance to gallstone formation, which suggests the potential future clinical relevance of the ,Klotho system. [source] Relevance between lipid metabolism-associated genes and rat liver regenerationHEPATOLOGY RESEARCH, Issue 8 2008Cunshuan Xu Aim:, Lipids are important in constituting cell structure and participating in many biological processes, particularly in energy supplementation to cells. The aim of the present study is to elucidate the action of lipid metabolism-associated genes on rat liver regeneration (LR). Methods:, Lipid metabolism-associated genes were obtained by collecting website data and retrieving related articles, and their expression changes in the regenerating rat liver were checked by the Rat Genome 230 2.0 array. Results:, In total, 280 genes involved in lipid metabolism were proven to be LR-associated by comparing the gene expression discrepancy between the partial-hepatectomy and sham-operation groups. The initial and total expression numbers of these genes occurring in the initial phase, G0/G1 transition, cell proliferation, cell differentiation, and structure,functional rebuilding of LR were 128, 33, 135, 6, and 267, 147, 1026, 306, respectively, illustrating that these genes were initially expressed mainly in the initiation stage and functioned in different phases. Upregulation (850 times) and downregulation (749 times), as well as 25 types of expression patterns, showed that the physiological and biochemical activities were diverse and complicated in LR. Conclusion:, According to the results of the chip detection, it was presumed that fatty acid synthesis at 24,66 h, leukotriene and androgen synthesis at 16,168 h, prostaglandin synthesis at 2,96 h, triglyceride synthesis at 18,24 h, glycosphingolipid synthesis at 0.5,66 h, metabolism of phosphatidyl inositol and sphingomyelin at 2,16 h, and cholesterol catabolism at 30,168 h were enhanced. Throughout almost the whole LR, the genes participating in estrogen, glucocorticoid, and progesterone synthesis, and triglyceride catabolism were upregulated, while phospholipid and glycosphingolipid catabolism were downregulated. [source] Hypolipidaemic effects of potato protein and fish protein in pigsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 4 2009J. Spielmann Summary This study was performed to assess the effects of potato protein and fish protein on concentrations of lipids in plasma and lipoproteins and the expression of genes involved in lipid metabolism in pigs used as an animal model. Therefore, 27 young male pigs with an average body weight of 22 kg were fed diets supplemented with protein extracted from potatoes (containing 849 g protein/kg dry matter), Alaska Pollack fillet as a source of fish protein (containing 926 g crude protein/kg dry matter) or casein which was used as control, for 3 weeks. Diets were formulated to supply identical amounts of each protein to the pigs by the three protein sources, namely 116 g/day in first week and 150 g/day in the second and third week. Pigs fed potato protein had lower concentrations of cholesterol in plasma and LDL than pigs fed casein (p < 0.05); no effect was observed on concentrations of HDL cholesterol and triglycerides. Pigs fed fish protein had lower cholesterol concentrations in plasma, LDL and HDL, and lower triglyceride concentrations in triglyceride-rich lipoproteins than pigs fed casein (p < 0.05). mRNA concentrations of genes involved in bile acid synthesis and cholesterol uptake were higher in pigs fed fish protein than in pigs fed casein (p < 0.05); no effect on these genes was observed in pigs fed potato protein. Expression of genes involved in lipogenesis and fatty acid oxidation was not altered by fish protein. In conclusion, this study shows that fish protein and potato protein lower plasma cholesterol concentrations in pigs. The hypocholesterolaemic effect of fish protein might be in part caused by a stimulation of bile acid synthesis; the reason for the hypocholesterolaemic effect of potato protein requires further elucidation. [source] The influence of dietary linoleic and , -linolenic acid on body composition and the activities of key enzymes of hepatic lipogenesis and fatty acid oxidation in mice,JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2007M. Javadi Summary We have recently suggested that feeding the C18 polyunsaturated fatty acid, , -linolenic acid (ALA), instead of linoleic acid (LA) reduced body fat in mice. However, the difference in body fat did not reach statistical significance, which prompted us to carry out this study using more animals and diets with higher contents of ALA and LA so that the contrast would be greater. The diets contained either 12% (w/w) LA and 3% ALA or 12% ALA and 4% LA. A low-fat diet was used as control. The diets were fed for 35 days. The proportion of body fat was not influenced by the type of dietary fatty acid. Plasma total cholesterol and phospholipids were significantly lower in ALA-fed mice than in mice fed LA. Activities of enzymes in the fatty acid oxidation pathway were significantly raised by these two diets when compared with the control diet. , -Linolenic acid vs. LA did not affect fatty acid oxidation enzymes. In mice fed the diet with LA activities of enzymes of de novo fatty acid synthesis were significantly decreased when compared with mice fed the control diet. , -Linolenic acid vs. LA feeding did not influence lipogenic enzymes. It is concluded that feeding mice for 35 days with diets either rich in LA or ALA did not significantly influence body composition. [source] Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiaeAGING CELL, Issue 4 2009Ashley L. Alvers Summary Following cessation of growth, yeast cells remain viable in a nondividing state for a period of time known as the chronological lifespan (CLS). Autophagy is a degradative process responsible for amino acid recycling in response to nitrogen starvation and amino acid limitation. We have investigated the role of autophagy during chronological aging of yeast grown in glucose minimal media containing different supplemental essential and nonessential amino acids. Deletion of ATG1 or ATG7, both of which are required for autophagy, reduced CLS, whereas deletion of ATG11, which is required for selective targeting of cellular components to the vacuole for degradation, did not reduce CLS. The nonessential amino acids isoleucine and valine, and the essential amino acid leucine, extended CLS in autophagy-deficient as well as autophagy-competent yeast. This extension was suppressed by constitutive expression of GCN4, which encodes a transcriptional regulator of general amino acid control (GAAC). Consistent with this, GCN4 expression was reduced by isoleucine and valine. Furthermore, elimination of the leucine requirement extended CLS and prevented the effects of constitutive expression of GCN4. Interestingly, deletion of LEU3, a GAAC target gene encoding a transcriptional regulator of branched side chain amino acid synthesis, dramatically increased CLS in the absence of amino acid supplements. In general, this indicates that activation of GAAC reduces CLS whereas suppression of GAAC extends CLS in minimal medium. These findings demonstrate important roles for autophagy and amino acid homeostasis in determining CLS in yeast. [source] The FIC1 gene: structure and polymorphisms in baboonJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2002Laura A. Cox A genome scan performed on 648 pedigreed baboons to detect and localize quantitative trait loci (QTL) for lipoprotein phenotypes that are known risk factors for atherosclerosis indicated the presence of a QTL on chromosome 18q that exerts a major influence on HDL-cholesterol (HDL-C) related phenotypes. Inspection of the human gene map revealed that the familial intrahepatic cholestatis gene 1 (FIC1) maps to the homologous region of baboon chromosome 18 containing the major QTL influencing HDL-C phenotypes. FIC1 is a strong biological candidate for this QTL because HDL-C is the preferred precursor for bile acid synthesis. In this study, we cloned and sequenced FIC1 cDNA and found that it is highly conserved between human and baboon. We also sequenced FIC1 cDNAs from a panel of unrelated baboons revealing single nucleotide polymorphisms (SNPs) and a polymorphic dinucleotide repeat. None of the baboon SNPs corresponded to human FIC1 mutations associated with familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis disorders. [source] Terephthalic acid synthesis at higher concentrations in high-temperature liquid water.AICHE JOURNAL, Issue 6 2009Abstract We synthesized terephthalic acid (TPA) from p -xylene at an initial concentration above its solubility limit in high-temperature liquid water (HTW). The nominal p -xylene loading at the reaction conditions was 0.4 mol L,1, which is the highest reported to date for generation of high TPA yields (>70 mol %) in HTW. The presence of two liquid phases during the reaction did not appear to accelerate the rate, unlike behavior reported for some other organic reactions done "on water" at lower temperatures. Adding oxygen gas in a large increment during synthesis produced a black liquid and a black solid byproduct, which is a previously undocumented problem. Adding oxygen in smaller increments prevented formation of the liquid and solid byproducts and also provided high selectivities (90 mol %) and yields (>70 mol %) of TPA. These results demonstrate the feasibility of HTW as a medium for TPA synthesis at p -xylene concentrations even higher than its solubility limit. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Terephthalic acid synthesis at higher concentrations in high-temperature liquid water.AICHE JOURNAL, Issue 3 2009Abstract We conducted terephthalic acid (TPA) synthesis from p-xylene in high-temperature liquid water (HTW) at 300°C. The p-xylene concentration at the reaction condition was 0.2 mol L,1, which is the highest to date in research that achieved at least 80 mol % yields of TPA in HTW. Pure oxygen gas was the oxidant. Increasing the MnBr2 catalyst concentration increased the rate of TPA formation only slightly. In contrast, whether oxygen was fed in small, quick, discrete bursts, or fed continuously significantly affected the p-xylene conversion and the TPA selectivity. Adding oxygen in quick bursts and small increments led to high selectivities (>90 mol %) of TPA. Continuous addition of oxygen failed to do so. In addition to identifying the sensitivity of this synthesis to the oxygen feed method, these results also demonstrate the feasibility of HTW for TPA synthesis at higher concentrations, and hence high TPA production per unit reactor volume. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Region-selective alterations of glucose oxidation and amino acid synthesis in the thiamine-deficient rat brain: a re-evaluation using 1H/13C nuclear magnetic resonance spectroscopyJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Darren Navarro Abstract Thiamine deficiency provides an effective model of selective neuronal cell death. 1H and 13C-NMR was used to investigate the effects of thiamine deficiency on the synthesis of amino acids derived from [1- 13C]glucose in vulnerable (medial thalamus; MT) compared to non-vulnerable (frontal cortex; FC) brain regions. Following 11 days of thiamine deficiency, a time-point associated with the absence of significant neuronal cell death, regional concentrations of glutamate, glutamine and GABA remained unaffected in FC and MT; however, decreased levels of aspartate in MT at this time-point were a predictor of regional vulnerability. De novo synthesis of glutamate and GABA were unaffected at 11 days of thiamine deficiency, while synthesis of [2- 13C]aspartate was significantly impaired. Glucose loading, which has been shown to exacerbate symptoms in patients with thiamine deficiency, resulted in further decreases of TCA cycle flux and reduced de novo synthesis of glutamate, aspartate and GABA in thiamine-deficient (TD) rats. Isotopomer analysis revealed that impaired TCA cycle flux and decreased aspartate synthesis due to thiamine deficiency occurred principally in neurons. Glucose loading deteriorated TD-related decreases in TCA cycle flux, and concomitantly reduced synthesis of aspartate and glutamate in MT. [source] ,-Amido boronic acids: A synthetic challenge and their properties as serine protease inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 2 2008Donald S. Matteson Abstract This review includes a personal account of the history of the development of the ,-amido boronic acid synthesis and related chemistry in the author's laboratory, as well as a review of some of the more significant developments that have occurred elsewhere more recently. The simple initial target, suggested by biochemist G. E. Lienhard, proved much more elusive to reach than anticipated.1 The circuitous effort that ultimately revealed the deceptively simple successful route,1 for which there is still no alternative, will be described. The properties of these compounds as enzyme inhibitors will be described very briefly. More extensive reviews of the enzyme inhibiting properties of ,-amido boronic acids have appeared recently.2 © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 233,246, 2008 [source] Chemical genomics: Functional analysis of orphan nuclear receptors in the regulation of bile acid metabolismMEDICINAL RESEARCH REVIEWS, Issue 6 2001Timothy M. Willson Abstract Chemical genomics is the name we have given to the analysis of gene function through use of small molecule chemical tools. Orphan nuclear receptors are ideally suited to this technique of functional analysis, since their activity as transcription factors is regulated by small hydrophobic ligands. GW4064 is a potent and selective nonsteroidal ligand for the nuclear bile acid receptor FXR (NR1H4). Using GW4064 as a chemical tool, we have identified genes regulated by FXR in the liver, including those involved in bile acid synthesis and transport. We have also discovered that PXR (NR1I2) is a lithocholic acid receptor that controls the biosynthesis and metabolism of bile acids. Together FXR and PXR cooperate to control biliary and urinary bile acid excretion. These functions suggest that potent PXR and FXR ligands may offer a new approach to the treatment of cholestatic liver disease. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 6, 513,522, 2001 [source] Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolismMOLECULAR MICROBIOLOGY, Issue 4 2006Aurélia Battesti Summary Bacteria respond to nutritional stresses by producing an intracellular alarmone, guanosine 5,-(tri)diphosphate, 3,-diphosphate [(p)ppGpp], which triggers the stringent response resulting in growth arrest and expression of resistance genes. In Escherichia coli, upon fatty acid or carbon starvation, SpoT enzyme activity switches from (p)ppGpp degradation to (p)ppGpp synthesis, but the signal and mechanism for this response remain totally unknown. Here, we characterize for the first time a physical interaction between SpoT and acyl carrier protein (ACP) using affinity co-purifications and two-hybrid in E. coli. ACP, as a central cofactor in fatty acid synthesis, may be an ideal candidate as a mediator signalling starvation to SpoT. Accordingly, we show that the ACP/SpoT interaction is specific of SpoT and ACP functions because ACP does not interact with the homologous RelA protein and because SpoT does not interact with a non-functional ACP. Using truncated SpoT fusion proteins, we demonstrate further that ACP binds the central TGS domain of SpoT, consistent with a role in regulation. The behaviours of SpoT point mutants that do not interact with ACP reveal modifications of the balance between the two opposite SpoT catalytic activities thereby changing (p)ppGpp levels. More importantly, these mutants fail to trigger (p)ppGpp accumulation in response to fatty acid synthesis inhibition, supporting the hypothesis that the ACP/SpoT interaction may be involved in SpoT-dependent stress response. This leads us to propose a model in which ACP carries information describing the status of cellular fatty acid metabolism, which in turn can trigger the conformational switch in SpoT leading to (p)ppGpp accumulation. [source] A bacterium that has three pathways to regulate membrane lipid fluidityMOLECULAR MICROBIOLOGY, Issue 2 2006John E. Cronan Summary Well-studied bacteria such as Bacillus subtilis and Escherichia coli each have only a single pathway for synthesis of the unsaturated fatty acids required to make functional membrane lipids. In marked contrast, unsaturated fatty acid synthesis in Pseudomonas aeruginosa proceeds by three distinct pathways. [source] Strange organelles ,Plasmodium mitochondria lack a pyruvate dehydrogenase complexMOLECULAR MICROBIOLOGY, Issue 1 2005Stuart A. Ralph Summary Our understanding of the Plasmodium mitochondrion and apicoplast has been greatly assisted by the genome sequence project. Sequence data have seeded recent research showing that the apicoplast is ,the ,site ,of ,several ,anabolic ,pathways ,including fatty acid synthesis. The discovery of an active apicoplast pyruvate dehydrogenase complex implies this enzyme generates the acetyl-CoA needed for fatty acid synthesis. However, the absence of a corresponding mitochondrial complex suggests that energy generation in Plasmodium is considerably different from pathways described in other eukaryotes. [source] | ||||||||||||||||||||||||||||||||||