Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.13 (acetyl-CoA synthetase)
 451 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of phenylacetate, phenylbutyrate, and phenylacetyl-CoA on the activity of choline acetyltransferase and S-acetyl-CoA synthetase was investigated in vitro. Phenylacetyl-CoA was found to be a very potent inhibitor of choline acetyltransferase, competitive for acetyl-CoA with Ki of 3.1 X 10(-7)M. In contrast, millimolar concentrations of phenylacetate and phenylbutyrate were required to inhibit the activity of the enzyme. Activity of S-acetyl-CoA synthetase was affected only slightly by the three agents in concentrations of 10(-3)-10(-2)M. At this time, results are interpreted to suggest that in phenylketonuria, phenylacetate exerts its neurotoxic action through its metabolic product, phenylacetyl-CoA, which could severely decrease the availability of acetyl-CoA.
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PMID:On the possible mechanism of phenylacetate neurotoxicity: inhibition of choline acetyltransferase by phenylacetyl-CoA. 614 28

The effect of hypolipidemic drugs, WY14643 and DH990, on plant lipid metabolism has been studied. The total incorporation of [14C]acetate into lipids was inhibited by addition of both drugs to aged potato (Solanum tuberosum) tuber discs, spinach (Spinacia oleracea) leaves, and spinach chloroplasts, while the incorporation in Chlorella vulgaris cells was affected only by DH990. Moreover, DH990 inhibited the incorporation of 14C-labeled fatty acids into phosphatidylcholine and phosphatidylethanolamine of potato discs, and decreased the incorporation into phosphatidylglycerol of Chlorella cells. DH990 inhibited the formation of polyunsaturated fatty acids in potato discs, Chlorella cells, and spinach leaves, whereas WY14643 had no effect on the formation of these fatty acids. Stearoyl-ACP desaturase from safflower (Carthamus tinctorius) seeds was very sensitive to both drugs, especially DH990, which completely blocked the activity at 2 mM levels. When safflower lysophospholipid acyltransferases were solubilized by detergent treatment, only DH990 inhibited the incorporation of [14C]oleoyl-CoA into lysophosphatidylcholine or lysophosphatidylethanolamine. Both drugs inhibited fatty acid synthesis from [14C]malonyl-CoA in the microsomal fraction from safflower seeds, but only DH990 inhibited FAS activity in the soluble fraction; both drugs inhibited severely the formation of stearic acid. Both acetyl-CoA carboxylase and acetyl-CoA synthetase were sensitive to both drugs.
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PMID:The effect of hypolipidemic drugs on plant lipid metabolism. 648 26

Two short-chain fatty acyl-CoA synthetases were extracted from the photosynthetic bacterium, Rhodopseudomonas sphaeroides, and partially purified by column chromatography on Sephacryl S-200 and DEAE-cellulose. One enzyme activated propionate, valerate, acrylate, butyrate, and acetate, and was designated as propionyl-CoA synthetase, since the highest activity and lowest Km value (0.6 mM) were observed with propionate. The other enzyme activated acetate, propionate and acrylate. It showed the highest activity and lowest Km value (0.37 mM) for acetate, and was identified as acetyl-CoA synthetase [EC 6.2.1.1].
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PMID:Short-chain acyl-coenzyme A synthetases in Rhodopseudomonas sphaeroides. 697 35

Some naturally occurring pseudoguaianolides and germacranolides as well as synthetic related compounds were observed to be antihyperlipidemic agents in mice. Several of these compounds at a dose of 20 mg/kg/day resulted in lowering of serum cholesterol by approximately 30% and of serum triglycerides by approximately 25%. Thiol-bearing enzymes of lipid synthesis, i.e., acetyl-CoA, citrate-lyase, acetyl-CoA synthetase, and beta-hydroxy-beta-methylglutaryl-CoA reductase, were inhibited by these agents in vitro, supporting the premise that these agents alkylate thiol nucleophiles by a Michael-type addition. The alpha-methylene-gamma-lactone moiety, the beta-unsubstituted cyclopentenone ring, and the alpha-epoxycyclopentanone system of these compounds appeared to be responsible for the lowering of serum lipids.
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PMID:Antihyperlipidemic activity of sesquiterpene lactones and related compounds. 720 85

1. The lipogenic enzyme ATP citrate lyase (ATP:citrate oxaloacetate-lyase (pro-3S-CH2COO-acetyl-CoA; ATP-dephosphorylating), EC 4.1.3.8) is partially purified from human liver by ammonium sulfate fractionation and anionexchange chromatography. 2. Km values for the substrates are 1.1 x 10(-5) 1.3 x 10(-3), and 1.2 x 10(-4) M for CoASH, ATP and citrate, respectively. The hypolipidemic drug L(-)-hydroxycitrate is a competitive inhibitor with respect to citrate (Ki = 3 x 10(-4) M). 3. Specific activities measured in liver, adipose tissue and intestinal mucosa (autopsic and biopsic material) are in the range of 1 mU/mg protein suggesting that the citrate pathway does not significantly contribute to human lipogenesis. No stimulation is found after a 3-day carbohydrate-rich diet. 4. Specific activities of other key-enzymes of the acetyl-CoA production from carbohydrates (pyruvate dehydrogenase, cytosolic acetyl-CoA synthetase) are of the same low magnitude.
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PMID:Properties and organ distribution of ATP citrate (pro-3S)-lyase. 741 78

Highly purified rat liver fatty acid synthetase is completely inhibited when assayed in the presence of a coenzyme A-depleting system such as that catalyzed by phosphotransacetylase, acetyl-CoA synthetase, or ATP citrate lyase. The addition of free CoA causes a reversal of this inhibition. The requirement of free CoA is the same whether acetyl-CoA or butyryl-CoA serves as the primer for fatty acid synthetase. The CoA-depleted and thus inactive fatty acid synthetase system can be reactivated by the addition of a rat brain thioesterase or a rat mammary gland thioesterase II preparation. This reactivation appears to occur in the absence of free CoA. Long chain fatty acids (mainly palmitate) are formed by the thioesterase reactivated system. These results suggest that CoA is required for the termination of the fatty acid synthetase reaction. Possible mechanisms are discussed.
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PMID:Coenzyme A requirement for the termination reaction of rat liver fatty acid synthetase. 743 Jan 43

In Escherichia coli carrying the poly(3-hydroxyalkanoate) (PHA) biosynthesis pathway on a plasmid (pha+), the function of the ackA (acetate kinase) and pta (phosphotransacetylase) genes is necessary for efficient incorporation of 3-hydroxyvalerate (3-HV) into the copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV)). Recombinant pha+ E. coli fadR atoC(Con) strains possessing mutations in ackA, pta, or both ackA and pta exhibited substantially reduced levels of 3-HV formation. Conversely, the same strains carrying the ackA gene on a multicopy plasmid exhibited an increase in 3-HV formation concomitant with a large increase in acetate kinase activity. However, if the strain possessing the multicopy ackA+ plasmid was mutant at the pta locus, it lost the ability to incorporate significant amounts of 3-HV into P(3HB-co-3HV). In addition to the ackA pta pathway, there is an inducible activity that can also mediate the incorporation of 3-HV into P(3HB-co-3HV). This pathway is repressed by glucose and is not normally operative in P(3HB-co-3HV) production in recombinant pha+ E. coli strains that are grown using glucose as the major carbon source. It appears likely that this activity is due to an inducible acetyl-CoA synthetase that converts propionate to propionyl-CoA.
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PMID:The function of ackA and pta genes is necessary for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis in recombinant pha+ Escherichia coli. 760 63

A number of earlier unknown 3'-dephospho-CoASH analogues with the pyrophosphate fragment replaced by an ester or phosphodiester bond were synthesized and tested in S-acetylation reaction, catalyzed by acetyl-CoA synthetase (EC 6.2.1.1) from rabbit myocardium. 3'-Dephospho-CoASH analogues with a phosphodiester bond, e.g. (Ia), had a lower affinity and diminished kinetic parameters than 3'-dephospho-CoASH (Km = 1 and 0.2 mM, respectively). The adenine substitution in (Ia) by guanine or hypoxanthine (but not cytosine) residue resulted in a loss of substrate properties. 3'-Dephospho-CoASH with an ester bond were not capable of accepting acetate under conditions used and only slightly inhibited the enzymic activity.
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PMID:[Analogs of 3'-dephospho-CoASH with a phosphodiester bond as substrates of the S-acetylation reaction, catalyzed by acetyl-CoA-synthetase fom rabbit myocardium]. 790 17

Acetyl-CoA synthetase activity in vitro is assayed quickly and conveniently by incubating whole chloroplasts, chloroplast extracts, or leaf extracts with labeled acetate, CoA, ATP, and Mg and transferring aliquots of the reaction mixture to pieces of either Whatman No. 1 or DE81 filter paper. Unreacted acetate is quantitatively washed from the papers while the acetyl-CoA, which binds quantitatively, is determined by scintillation counting. Enzyme activity is absolutely dependent upon the presence of CoA, ATP, and Mg in reaction mixtures. The reaction has a broad pH optimum around pH 8.5. Potassium is required for maximum activity, and lithium strongly inhibits the reaction. The product retained on the papers was characterized as acetyl-CoA by several methods. On a chlorophyll basis, acetyl-CoA synthetase activities were about 25% higher in leaf homogenates than in intact chloroplasts isolated from similar leaves. Enzyme activities in the optimized assay were three- to fourfold greater than previously reported.
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PMID:On the assay of acetyl-CoA synthetase activity in chloroplasts and leaf extracts. 790 45

Saccharomyces cerevisiae T23C (pda1::Tn5ble) is an isogenic gene replacement mutant of the wild-type strain S. cerevisiae T23D. The mutation causes a complete loss of pyruvate dehydrogenase activity. Pyruvate metabolism in this pyruvate-dehydrogenase-negative (Pdh-) strain was investigated in aerobic glucose-limited chemostat cultures, grown at a dilution rate of 0.10 h-1, and compared with the metabolism in the isogenic wild-type strain. Under these conditions, growth of the Pdh- strain was fully respiratory. Enzyme activities in cell-free extracts indicated that the enzymes pyruvate decarboxylase, acetaldehyde dehydrogenase and acetyl-coenzyme A (acetyl-CoA) synthetase could provide a functional bypass of the pyruvate dehydrogenase complex. Since this metabolic sequence involves ATP hydrolysis in the acetyl-CoA synthetase reaction, a negative effect of the pda1::Tn5ble mutation on the growth efficiency was anticipated. Indeed, the biomass yield of the Pdh- strain [0.44 g biomass (g glucose)-1] was significantly lower than that of wild-type S. cerevisiae [0.52 g biomass (g glucose)-1]. The effect of the mutation on biomass yield could be quantitatively explained in terms of a lower ATP yield from glucose catabolism and an increased ATP requirement for the synthesis of acetyl-CoA used in anabolism. Control experiments showed that the pda1::Tn5ble mutation did not affect biomass yield in ethanol-limited chemostat cultures. The results support the view that, during aerobic glucose-limited growth of S. cerevisiae at low growth rates, the pyruvate dehydrogenase complex accounts for the major part of the pyruvate flux. Moreover, it is concluded that hydrolysis of pyrophosphate formed in the acetyl-CoA synthetase reaction does not contribute significantly to energy transduction in this yeast. Respiratory-deficient cells did not contribute to glucose metabolism in the chemostat cultures and were probably formed upon plating.
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PMID:Energetic aspects of glucose metabolism in a pyruvate-dehydrogenase-negative mutant of Saccharomyces cerevisiae. 801 82


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