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Pesquisa : D08.811.277.352.897.075 [Categoria DeCS]
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[PMID]:25852051
[Au] Autor:Chen Y; Zhang Y; Siewers V; Nielsen J
[Ad] Endereço:Department of Biology & Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden;
[Ti] Título:Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase.
[So] Source:FEMS Yeast Res;15(3), 2015 May.
[Is] ISSN:1567-1364
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central carbon metabolism, but also an important precursor metabolite for native or engineered pathways that can produce many products of commercial interest such as pharmaceuticals, chemicals or biofuels. In the yeast Saccharomyces cerevisiae, acetyl-CoA is compartmentalized in the cytosol, mitochondrion, peroxisome and nucleus, and cannot be directly transported between these compartments. With the acetyl-carnitine or glyoxylate shuttle, acetyl-CoA produced in peroxisomes or the cytoplasm can be transported into the cytoplasm or the mitochondria. However, whether acetyl-CoA generated in the mitochondria can be exported to the cytoplasm is still unclear. Here, we investigated whether the transfer of acetyl-CoA from the mitochondria to the cytoplasm can occur using a pyruvate decarboxylase negative, non-fermentative yeast strain. We found that mitochondrial Ach1 can convert acetyl-CoA in this compartment into acetate, which crosses the mitochondrial membrane before being converted into acetyl-CoA in the cytosol. Based on our finding we propose a model in which acetate can be used to exchange acetyl units between mitochondria and the cytosol. These results will increase our fundamental understanding of intracellular transport of acetyl units, and also help to develop microbial cell factories for many kinds of acetyl-CoA derived products.
[Mh] Termos MeSH primário: Ácido Acético/metabolismo
Acetilcoenzima A/metabolismo
Acetil-CoA Hidrolase/metabolismo
Coenzima A-Transferases/metabolismo
Citosol/química
Mitocôndrias/enzimologia
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/enzimologia
[Mh] Termos MeSH secundário: Mitocôndrias/metabolismo
Piruvato Descarboxilase/deficiência
Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Saccharomyces cerevisiae Proteins); 72-89-9 (Acetyl Coenzyme A); EC 2.8.3.- (Ach1 protein, S cerevisiae); EC 2.8.3.- (Coenzyme A-Transferases); EC 3.1.2.1 (Acetyl-CoA Hydrolase); EC 4.1.1.1 (Pyruvate Decarboxylase); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150424
[Lr] Data última revisão:
150424
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150409
[St] Status:MEDLINE


  2 / 68 MEDLINE  
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[PMID]:25768301
[Au] Autor:Gao J; Kim HM; Elia AE; Elledge SJ; Colaiácovo MP
[Ad] Endereço:Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
[Ti] Título:NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA metabolism to the initiation of recombination during C. elegans meiosis.
[So] Source:PLoS Genet;11(3):e1005029, 2015 Mar.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The formation of DNA double-strand breaks (DSBs) must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation.
[Mh] Termos MeSH primário: Acetilcoenzima A/metabolismo
Acetil-CoA Hidrolase/metabolismo
Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/genética
Caenorhabditis elegans/metabolismo
Recombinação Genética
[Mh] Termos MeSH secundário: Acetilação
Animais
Quebras de DNA de Cadeia Dupla
Histonas/metabolismo
Cromossomo X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CRA-1 protein, C elegans); 0 (Caenorhabditis elegans Proteins); 0 (Histones); 72-89-9 (Acetyl Coenzyme A); EC 3.1.2.1 (ACER-1 protein, C elegans); EC 3.1.2.1 (Acetyl-CoA Hydrolase)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150314
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1005029


  3 / 68 MEDLINE  
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[PMID]:24823794
[Au] Autor:Laurieri N; Dairou J; Egleton JE; Stanley LA; Russell AJ; Dupret JM; Sim E; Rodrigues-Lima F
[Ad] Endereço:Department of Pharmacology, University of Oxford, Oxford, United Kingdom; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, United Kingdom.
[Ti] Título:From arylamine N-acetyltransferase to folate-dependent acetyl CoA hydrolase: impact of folic acid on the activity of (HUMAN)NAT1 and its homologue (MOUSE)NAT2.
[So] Source:PLoS One;9(5):e96370, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acetyl Coenzyme A-dependent N-, O- and N,O-acetylation of aromatic amines and hydrazines by arylamine N-acetyltransferases is well characterised. Here, we describe experiments demonstrating that human arylamine N-acetyltransferase Type 1 and its murine homologue (Type 2) can also catalyse the direct hydrolysis of acetyl Coenzyme A in the presence of folate. This folate-dependent activity is exclusive to these two isoforms; no acetyl Coenzyme A hydrolysis was found when murine arylamine N-acetyltransferase Type 1 or recombinant bacterial arylamine N-acetyltransferases were incubated with folate. Proton nuclear magnetic resonance spectroscopy allowed chemical modifications occurring during the catalytic reaction to be analysed in real time, revealing that the disappearance of acetyl CH3 from acetyl Coenzyme A occurred concomitantly with the appearance of a CH3 peak corresponding to that of free acetate and suggesting that folate is not acetylated during the reaction. We propose that folate is a cofactor for this reaction and suggest it as an endogenous function of this widespread enzyme. Furthermore, in silico docking of folate within the active site of human arylamine N-acetyltransferase Type 1 suggests that folate may bind at the enzyme's active site, and facilitate acetyl Coenzyme A hydrolysis. The evidence presented in this paper adds to our growing understanding of the endogenous roles of human arylamine N-acetyltransferase Type 1 and its mouse homologue and expands the catalytic repertoire of these enzymes, demonstrating that they are by no means just xenobiotic metabolising enzymes but probably also play an important role in cellular metabolism. These data, together with the characterisation of a naphthoquinone inhibitor of folate-dependent acetyl Coenzyme A hydrolysis by human arylamine N-acetyltransferase Type 1/murine arylamine N-acetyltransferase Type 2, open up a range of future avenues of exploration, both for elucidating the developmental role of these enzymes and for improving chemotherapeutic approaches to pathological conditions including estrogen receptor-positive breast cancer.
[Mh] Termos MeSH primário: Acetil-CoA Hidrolase/metabolismo
Acetiltransferases/metabolismo
Arilamina N-Acetiltransferase/metabolismo
Ácido Fólico/metabolismo
Isoenzimas/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Animais
Seres Humanos
Hidrólise
Camundongos
Ressonância Magnética Nuclear Biomolecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Isoenzymes); 935E97BOY8 (Folic Acid); EC 2.3.1.- (Acetyltransferases); EC 2.3.1.118 (N-hydroxyarylamine O-acetyltransferase); EC 2.3.1.5 (Arylamine N-Acetyltransferase); EC 2.3.1.5 (N-acetyltransferase 1); EC 3.1.2.1 (Acetyl-CoA Hydrolase)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140515
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0096370


  4 / 68 MEDLINE  
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[PMID]:24192375
[Au] Autor:Khandokar YB; Londhe A; Patil S; Forwood JK
[Ad] Endereço:School of Biomedical Sciences, Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales 2650, Australia.
[Ti] Título:Expression, purification and crystallization of acetyl-CoA hydrolase from Neisseria meningitidis.
[So] Source:Acta Crystallogr Sect F Struct Biol Cryst Commun;69(Pt 11):1303-6, 2013 Nov.
[Is] ISSN:1744-3091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Neisseria meningitidis is the causative microorganism of many human diseases, including bacterial meningitis; together with Streptococcus pneumoniae, it accounts for approximately 80% of bacterial meningitis infections. The emergence of antibiotic-resistant strains of N. meningitidis has created a strong urgency for the development of new therapeutics, and the high-resolution structural elucidation of enzymes involved in cell metabolism represents a platform for drug development. Acetyl-CoA hydrolase is involved in multiple functions in the bacterial cell, including membrane synthesis, fatty-acid and lipid metabolism, gene regulation and signal transduction. Here, the first recombinant protein expression, purification and crystallization of a hexameric acetyl-CoA hydrolase from N. meningitidis are reported. This protein was crystallized using the hanging-drop vapour-diffusion technique at pH 8.5 and 290 K using ammonium phosphate as a precipitant. Optimized crystals diffracted to 2.0 Šresolution at the Australian Synchrotron and belonged to space group P2(1)3 (unit-cell parameters a = b = c = 152.2 Å), with four molecules in the asymmetric unit.
[Mh] Termos MeSH primário: Acetil-CoA Hidrolase/química
Acetil-CoA Hidrolase/isolamento & purificação
Proteínas de Bactérias/química
Proteínas de Bactérias/isolamento & purificação
Neisseria meningitidis/enzimologia
[Mh] Termos MeSH secundário: Cristalização
Eletroforese em Gel de Poliacrilamida
Seres Humanos
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 3.1.2.1 (Acetyl-CoA Hydrolase)
[Em] Mês de entrada:1406
[Cu] Atualização por classe:151101
[Lr] Data última revisão:
151101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131107
[St] Status:MEDLINE
[do] DOI:10.1107/S1744309113028042


  5 / 68 MEDLINE  
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[PMID]:23709691
[Au] Autor:Horibata Y; Ando H; Itoh M; Sugimoto H
[Ad] Endereço:Department of Biochemistry, Dokkyo Medical University School of Medicine, Tochigi, Japan.
[Ti] Título:Enzymatic and transcriptional regulation of the cytoplasmic acetyl-CoA hydrolase ACOT12.
[So] Source:J Lipid Res;54(8):2049-59, 2013 Aug.
[Is] ISSN:1539-7262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acyl-CoA thioesterase 12 (ACOT12) is the major enzyme known to hydrolyze the thioester bond of acetyl-CoA in the cytosol in the liver. ACOT12 contains a catalytic thioesterase domain at the N terminus and a steroidogenic acute regulatory protein-related lipid transfer (START) domain at the C terminus. We investigated the effects of lipids (phospholipids, sphingolipids, fatty acids, and sterols) on ACOT12 thioesterase activity and found that the activity was inhibited by phosphatidic acid (PA) in a noncompetitive manner. In contrast, the enzymatic activity of a mutant form of ACOT12 lacking the START domain was not inhibited by the lipids. These results suggest that the START domain is important for regulation of ACOT12 activity by PA. We also found that PA could bind to thioesterase domain, but not to the START domain, and had no effect on ACOT12 dissociation. ACOT12 is detectable in the liver but not in hepatic cell lines such as HepG2, Hepa-1, and Fa2N-4. ACOT12 mRNA and protein levels in rat primary hepatocytes decreased following treatment with insulin. These results suggest that cytosolic acetyl-CoA levels in the liver are controlled by lipid metabolites and hormones, which result in allosteric enzymatic and transcriptional regulation of ACOT12.
[Mh] Termos MeSH primário: Acetil-CoA Hidrolase/genética
Acetil-CoA Hidrolase/metabolismo
Citoplasma/enzimologia
Transcrição Genética/genética
[Mh] Termos MeSH secundário: Acetil-CoA Hidrolase/antagonistas & inibidores
Acetil-CoA Hidrolase/deficiência
Animais
Insulina/farmacologia
Lipídeos/biossíntese
Fígado/enzimologia
Fígado/metabolismo
Dados de Sequência Molecular
Ácidos Fosfatídicos/farmacologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Ratos
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insulin); 0 (Lipids); 0 (Phosphatidic Acids); 0 (RNA, Messenger); EC 3.1.2.1 (Acetyl-CoA Hydrolase)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:160307
[Lr] Data última revisão:
160307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130528
[St] Status:MEDLINE
[do] DOI:10.1194/jlr.M030163


  6 / 68 MEDLINE  
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[PMID]:22705155
[Au] Autor:Alves MG; Socorro S; Silva J; Barros A; Sousa M; Cavaco JE; Oliveira PF
[Ad] Endereço:University of Beira Interior, Covilhã, Portugal.
[Ti] Título:In vitro cultured human Sertoli cells secrete high amounts of acetate that is stimulated by 17ß-estradiol and suppressed by insulin deprivation.
[So] Source:Biochim Biophys Acta;1823(8):1389-94, 2012 Aug.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Several important functions for a successful spermatogenesis are dependent on Sertoli cells (SCs). Besides their unique characteristics as support cells, they produce essential cofactors and metabolites, and are responsible for nurturing the developing germ cells. The continuous production of lipids, phospholipids and proteins by germ cells must require high amounts of metabolic precursors. Thus, we hypothesized that hSCs could produce acetate in a hormonally-regulated manner. METHODS: hSC-enriched primary cultures were maintained in the absence of insulin or in the presence of 17ß-estradiol (E2) or 5α-dihydrotestosterone (DHT). Acetate production was determined by 1H-NMR. mRNA gene expression levels of Acetyl CoA hydrolase (ACoA Hyd) and Acetyl CoA synthase (ACoA Synt) were determined by RT-PCR. RESULTS: hSCs produced high amounts of acetate suggesting that this metabolite should play a key role on the progression of spermatogenesis, namely as a metabolic precursor for the synthesis of cellular constituents. In addition, acetate metabolism proved to be under strict hormonal regulation. In the presence of E2 or DHT, hSCs produced different amounts of acetate. While E2 treatment increased acetate production, increasing ACoA Hyd gene transcript levels, DHT-treated cells showed decreased acetate production, differently modulating the ratio ACoA Hyd/ACoA Synt. Surprisingly, insulin-deprivation completely suppressed acetate production/export and significantly decreased the ACoA Hyd gene transcript levels. GENERAL SIGNIFICANCE: Taken together, these results suggest that, although hSCs are primarily described as lactate producers, the elevated production of acetate deserves special attention, in order to clarify the mechanisms behind its hormonal regulation and its role on a successful spermatogenesis.
[Mh] Termos MeSH primário: Acetatos/metabolismo
Estradiol/fisiologia
Insulina/fisiologia
Células de Sertoli/secreção
[Mh] Termos MeSH secundário: Acetil-CoA Hidrolase/genética
Acetil-CoA Hidrolase/metabolismo
Androgênios/farmacologia
Androgênios/fisiologia
Células Cultivadas
Di-Hidrotestosterona/farmacologia
Estradiol/farmacologia
Expressão Gênica
Seres Humanos
Insulina/deficiência
Masculino
Células de Sertoli/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetates); 0 (Androgens); 0 (Insulin); 08J2K08A3Y (Dihydrotestosterone); 4TI98Z838E (Estradiol); EC 3.1.2.1 (Acetyl-CoA Hydrolase)
[Em] Mês de entrada:1302
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120619
[St] Status:MEDLINE
[do] DOI:10.1016/j.bbamcr.2012.06.002


  7 / 68 MEDLINE  
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[PMID]:22474284
[Au] Autor:Millerioux Y; Morand P; Biran M; Mazet M; Moreau P; Wargnies M; Ebikeme C; Deramchia K; Gales L; Portais JC; Boshart M; Franconi JM; Bringaud F
[Ad] Endereço:Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536, Université Bordeaux Segalen, CNRS, 146 Rue Léo Saignat, 33076 Bordeaux, France.
[Ti] Título:ATP synthesis-coupled and -uncoupled acetate production from acetyl-CoA by mitochondrial acetate:succinate CoA-transferase and acetyl-CoA thioesterase in Trypanosoma.
[So] Source:J Biol Chem;287(21):17186-97, 2012 May 18.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Insect stage trypanosomes use an "acetate shuttle" to transfer mitochondrial acetyl-CoA to the cytosol for the essential fatty acid biosynthesis. The mitochondrial acetate sources are acetate:succinate CoA-transferase (ASCT) and an unknown enzymatic activity. We have identified a gene encoding acetyl-CoA thioesterase (ACH) activity, which is shown to be the second acetate source. First, RNAi-mediated repression of ASCT in the ACH null background abolishes acetate production from glucose, as opposed to both single ASCT and ACH mutants. Second, incorporation of radiolabeled glucose into fatty acids is also abolished in this ACH/ASCT double mutant. ASCT is involved in ATP production, whereas ACH is not, because the ASCT null mutant is ∼1000 times more sensitive to oligomycin, a specific inhibitor of the mitochondrial F(0)/F(1)-ATP synthase, than wild-type cells or the ACH null mutant. This was confirmed by RNAi repression of the F(0)/F(1)-ATP synthase F(1)ß subunit, which is lethal when performed in the ASCT null background but not in the wild-type cells or the ACH null background. We concluded that acetate is produced from both ASCT and ACH; however, only ASCT is responsible, together with the F(0)/F(1)-ATP synthase, for ATP production in the mitochondrion.
[Mh] Termos MeSH primário: Acetatos/metabolismo
Acetilcoenzima A/metabolismo
Acetil-CoA Hidrolase/metabolismo
Trifosfato de Adenosina/biossíntese
Coenzima A-Transferases/metabolismo
Mitocôndrias/enzimologia
Proteínas Mitocondriais/metabolismo
Proteínas de Protozoários/metabolismo
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Acetilcoenzima A/genética
Acetil-CoA Hidrolase/genética
Coenzima A-Transferases/genética
Ácidos Graxos/genética
Ácidos Graxos/metabolismo
Glucose/genética
Glucose/metabolismo
Mitocôndrias/genética
Proteínas Mitocondriais/genética
Mutação
ATPases Translocadoras de Prótons/genética
ATPases Translocadoras de Prótons/metabolismo
Proteínas de Protozoários/genética
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetates); 0 (Fatty Acids); 0 (Mitochondrial Proteins); 0 (Protozoan Proteins); 72-89-9 (Acetyl Coenzyme A); 8L70Q75FXE (Adenosine Triphosphate); EC 2.8.3.- (Coenzyme A-Transferases); EC 3.1.2.1 (Acetyl-CoA Hydrolase); EC 3.6.3.14 (Proton-Translocating ATPases); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1207
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120405
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M112.355404


  8 / 68 MEDLINE  
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[PMID]:20237302
[Au] Autor:Lin X; Shim K; Odle J
[Ad] Endereço:Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC 27695, USA.
[Ti] Título:Carnitine palmitoyltransferase I control of acetogenesis, the major pathway of fatty acid {beta}-oxidation in liver of neonatal swine.
[So] Source:Am J Physiol Regul Integr Comp Physiol;298(5):R1435-43, 2010 May.
[Is] ISSN:1522-1490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To examine the regulation of hepatic acetogenesis in neonatal swine, carnitine palmitoyltransferase I (CPT I) activity was measured in the presence of varying palmitoyl-CoA (substrate) and malonyl-CoA (inhibitor) concentrations, and [1-(14)C]-palmitate oxidation was simultaneously measured. Accumulation rates of (14)C-labeled acetate, ketone bodies, and citric acid cycle intermediates within the acid-soluble products were determined using radio-HPLC. Measurements were conducted in mitochondria isolated from newborn, 24-h (fed or fasted), and 5-mo-old pigs. Acetate rather than ketone bodies was the predominant radiolabeled product, and its production increased twofold with increasing fatty acid oxidation during the first 24-h suckling period. The rate of acetogenesis was directly proportional to CPT I activity. The high activity of CPT I in 24-h-suckling piglets was not attributable to an increase in CPT I gene expression, but rather to a large decrease in the sensitivity of CPT I to malonyl-CoA inhibition, which offset a developmental decrease in affinity of CPT I for palmitoyl-CoA. Specifically, the IC(50) for malonyl-CoA inhibition and K(m) value for palmitoyl-CoA measured in 24-h-suckling pigs were 1.8- and 2.7-fold higher than measured in newborn pigs. The addition of anaplerotic carbon from malate (10 mM) significantly reduced (14)C accumulation in acetate (P < 0.003); moreover, the reduction was much greater in newborn (80%) than in 24-h-fed (72%) and 5-mo-old pigs (55%). The results demonstrate that acetate is the primary product of hepatic mitochondrial beta-oxidation in Sus scrofa and that regulation during early development is mediated primarily via kinetic modulation of CPT I.
[Mh] Termos MeSH primário: Acetatos/metabolismo
Carnitina O-Palmitoiltransferase/metabolismo
Ácidos Graxos/metabolismo
Fígado/enzimologia
Sus scrofa/metabolismo
[Mh] Termos MeSH secundário: Acetil-CoA Hidrolase/metabolismo
Fatores Etários
Animais
Animais Lactentes
Radioisótopos de Carbono
Carnitina O-Palmitoiltransferase/genética
Ácido Cítrico/metabolismo
Ciclo do Ácido Cítrico/fisiologia
Ativação Enzimática/fisiologia
Regulação Enzimológica da Expressão Gênica
Corpos Cetônicos/metabolismo
Malonil Coenzima A/metabolismo
Mitocôndrias/metabolismo
Mitocôndrias Hepáticas/enzimologia
Oxirredução
Palmitatos/farmacocinética
Palmitoil Coenzima A/metabolismo
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Acetates); 0 (Carbon Radioisotopes); 0 (Fatty Acids); 0 (Ketone Bodies); 0 (Palmitates); 0 (RNA, Messenger); 1763-10-6 (Palmitoyl Coenzyme A); 2968PHW8QP (Citric Acid); 524-14-1 (Malonyl Coenzyme A); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase); EC 3.1.2.1 (Acetyl-CoA Hydrolase)
[Em] Mês de entrada:1009
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100319
[St] Status:MEDLINE
[do] DOI:10.1152/ajpregu.00634.2009


  9 / 68 MEDLINE  
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[PMID]:19298859
[Au] Autor:Fleck CB; Brock M
[Ad] Endereço:Leibniz Institute for Natural Product Research and Infection Biology e.V., -Hans Knoell Institute-, Research Group Microbial Biochemistry and Physiology, Jena, Germany.
[Ti] Título:Re-characterisation of Saccharomyces cerevisiae Ach1p: fungal CoA-transferases are involved in acetic acid detoxification.
[So] Source:Fungal Genet Biol;46(6-7):473-85, 2009 Jun-Jul.
[Is] ISSN:1096-0937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Saccharomyces cerevisiae and Neurospora crassa mutants defective in the so-called acetyl-CoA hydrolases Ach1p and Acu-8, respectively, display a severe growth defect on acetate, which is most strongly pronounced under acidic conditions. Acetyl-CoA hydrolysis is an energy wasting process and therefore denoted as a biochemical conundrum. Acetyl-CoA hydrolases show high sequence identity to the CoA-transferase CoaT from Aspergillus nidulans. Therefore, we extensively re-characterised the yeast enzyme. Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. Complementation of an ach1 mutant with the coaT gene reversed the growth defect on acetate confirming the in vivo function of Ach1p as a CoA-transferase. Our results imply that Ach1p is involved in mitochondrial acetate detoxification by a CoASH transfer from succinyl-CoA to acetate. Thereby, Ach1p does not perform the energy wasting hydrolysis of acetyl-CoA but conserves energy by the detoxification of mitochondrial acetate.
[Mh] Termos MeSH primário: Ácido Acético/metabolismo
Acetil-CoA Hidrolase/química
Proteínas de Saccharomyces cerevisiae/química
Saccharomyces cerevisiae/enzimologia
[Mh] Termos MeSH secundário: Acetilcoenzima A/metabolismo
Acetil-CoA Hidrolase/genética
Acetil-CoA Hidrolase/isolamento & purificação
Acetil-CoA Hidrolase/metabolismo
Cinética
Mitocôndrias/química
Mitocôndrias/enzimologia
Mitocôndrias/genética
Mitocôndrias/metabolismo
Saccharomyces cerevisiae/química
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/isolamento & purificação
Proteínas de Saccharomyces cerevisiae/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Saccharomyces cerevisiae Proteins); 72-89-9 (Acetyl Coenzyme A); EC 3.1.2.1 (Acetyl-CoA Hydrolase); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:0906
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:090321
[St] Status:MEDLINE
[do] DOI:10.1016/j.fgb.2009.03.004


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[PMID]:18689527
[Au] Autor:Carman AJ; Vylkova S; Lorenz MC
[Ad] Endereço:Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center atHouston, Houston, Texas 77030, USA.
[Ti] Título:Role of acetyl coenzyme A synthesis and breakdown in alternative carbon source utilization in Candida albicans.
[So] Source:Eukaryot Cell;7(10):1733-41, 2008 Oct.
[Is] ISSN:1535-9786
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acetyl coenzyme A (acetyl-CoA) is the central intermediate of the pathways required to metabolize nonfermentable carbon sources. Three such pathways, i.e., gluconeogenesis, the glyoxylate cycle, and beta-oxidation, are required for full virulence in the fungal pathogen Candida albicans. These processes are compartmentalized in the cytosol, mitochondria, and peroxosomes, necessitating transport of intermediates across intracellular membranes. Acetyl-CoA is trafficked in the form of acetate by the carnitine shuttle, and we hypothesized that the enzymes that convert acetyl-CoA to/from acetate, i.e., acetyl-CoA hydrolase (ACH1) and acetyl-CoA synthetase (ACS1 and ACS2), would regulate alternative carbon utilization and virulence. We show that C. albicans strains depleted for ACS2 are unviable in the presence of most carbon sources, including glucose, acetate, and ethanol; these strains metabolize only fatty acids and glycerol, a substantially more severe phenotype than that of Saccharomyces cerevisiae acs2 mutants. In contrast, deletion of ACS1 confers no phenotype, though it is highly induced in the presence of fatty acids, perhaps explaining why acs2 mutants can utilize fatty acids. Strains lacking ACH1 have a mild growth defect on some carbon sources but are fully virulent in a mouse model of disseminated candidiasis. Both ACH1 and ACS2 complement mutations in their S. cerevisiae homolog. Together, these results show that acetyl-CoA metabolism and transport are critical for growth of C. albicans on a wide variety of nutrients. Furthermore, the phenotypic differences between mutations in these highly conserved genes in S. cerevisiae and C. albicans support recent findings that significant functional divergence exists even in fundamental metabolic pathways between these related yeasts.
[Mh] Termos MeSH primário: Acetilcoenzima A/metabolismo
Candida albicans/metabolismo
Carbono/metabolismo
[Mh] Termos MeSH secundário: Acetato-CoA Ligase/genética
Acetato-CoA Ligase/metabolismo
Acetil-CoA Hidrolase/genética
Acetil-CoA Hidrolase/metabolismo
Animais
Candida albicans/enzimologia
Candida albicans/genética
Candida albicans/patogenicidade
Candidíase/microbiologia
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Teste de Complementação Genética
Camundongos
Mutação
Saccharomyces cerevisiae/enzimologia
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Fungal Proteins); 72-89-9 (Acetyl Coenzyme A); 7440-44-0 (Carbon); EC 3.1.2.1 (Acetyl-CoA Hydrolase); EC 6.2.1.1 (Acetate-CoA Ligase)
[Em] Mês de entrada:0811
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:080812
[St] Status:MEDLINE
[do] DOI:10.1128/EC.00253-08



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