Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malonyl-CoA decarboxylase from the uropygial gland of goose decarboxylated (R,S)-methylmalonyl-CoA at a slow rate and introduced 3H from [3H]2O into the resulting propionyl-CoA. Carboxylation of this labeled propionyl-CoA by propionyl-CoA carboxylase from pig heart and acetyl-CoA carboxylase from the uropygial gland completely removed 3H. Repeated treatment of (R,S)-[methyl-14C]methylmalonyl-CoA with the decarboxylase converted 50% of the substrate into propionyl-CoA, whereas (S)-methylmalonyl-CoA, generated by both carboxylases, was completely decarboxylated. Radioactive (R)- (S), and (R,S)-methylmalonyl-CoA were equally incorporated into fatty acids by fatty acid synthetase from the uropygial gland. The residual methylmalonyl-CoA remaining after fatty acid synthetase reaction on (R,S)-methylmalonyl-CoA was also racemic. These results show that: (a) the decarboxylase is stereospecific, (b) replacement of the carboxyl group by hydrogen occurs with retention of configuration, (c) acetyl-CoA carboxylase of the uropygial gland generates (S)-methylmalonyl-CoA from propionyl-CoA, and (d) fatty acid synthetase is not stereospecific for methylmalonyl-CoA.
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PMID:Stereospecificity of malonyl-CoA decarboxylase, acetyl-CoA carboxylase, and fatty acid synthetase from the uropygial gland of goose. 610 30

The activities of acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthetase (FAS) and beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.88) were determined in subcellular fractions of livers from chicks fed different cereal-based diets. With a barley-based diet as compared to corn, the following was observed: body and liver weights decreased 31%; HMG-CoA reductase activity of liver decreased 79%; acetyl-CoA carboxylase activity increased 3-fold; fatty acid synthesis increased 5-fold, and plasma and liver cholesterol decreased 45% and 35%, respectively. The suppression and induction of activities of the two divergent pathways (cholesterol and fatty acid biosynthesis) persisted for at least 21 days. Wheat, oats and rye showed a similar but less pronounced effect. The pronounced decrease in plasma cholesterol level and HMG-CoA reductase activity have implications for human nutrition and possible control of the cardiovascular diseases in which cholesterol plays a key role.
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PMID:Regulation of lipid metabolism in chicken liver by dietary cereals. 610 15

The interaction of stearoyl-(1,N6)-etheno coenzyme A (stearoyl-epsilon-CoA) with acetyl coenzyme A carboxylase was investigated by using fluorescence spectroscopy. The fluorescence emission of stearoyl-epsilon-CoA was partially quenched by acetyl coenzyme A carboxylase. Analysis of the data for dissociation constant (KD) and the stoichiometry of the interaction (n) gave values of 5.06 nM and 1.2, respectively, at pH 7.6 in 50 mM Tris-HCl and 25 degrees C. The KD value is comparable to the inhibition constant (Ki) obtained previously by others for the inhibition of rat liver acetyl coenzyme A carboxylase by long chain fatty acyl-CoAs. Citrate (which is known to polymerize and thus activate carboxylase) caused a partial quenching of the protein fluorescence of carboxylase, presumably due to polymerization of the enzyme. The quenching of the stearoyl-epsilon-CoA fluorescence caused by carboxylase as well as the inhibition of carboxylase activity by stearoyl-epsilon-CoA was reversed by citrate, but only in the presence of 6-O-methylglucose polysaccharide which forms a stable complex with fatty acyl-CoA. This shows that the stearoyl-epsilon-CoA bound to the enzyme is displaced by citrate only in the presence of an acceptor of fatty acyl-CoA. These results support the reciprocal relationship of citrate and fatty acyl-CoA in the regulation of acetyl coenzyme A carboxylase.
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PMID:Interaction of the fluorescent analogue stearoyl-(1,N6)-etheno coenzyme A with chicken liver acetyl coenzyme A carboxylase. 610 64

Acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] is activated by physiological concentrations of CoA. The CoA concentration dependency of this activation is sigmoidal; below 60 microM there is little or no activation, but the activation observed between 60 and 120 microM indicates that small changes in the concentration of CoA can cause significant changes in carboxylase activity. CoA activation of acetyl-CoA crboxylase accompanies polymerization of acetyl-CoA carboxylase. However, the binding site for CoA appears to be different from that of citrate. In contrast to citrate activation, which changes only the Vmax of the reaction, CoA activation of carboxylase results in polymeric forms with a lower Km for acetyl-CoA. The Km for acetyl-CoA is 0.4 mM in the control enzyme, whereas that of the CoA-activated enzyme is as low as 4 microM. The Km for ATP was not changed. Derivatives of CoA were not effective in activating the carboxylase, indicating that the CoA effect is specific. Arguments are presented that CoA could be a physiologically significant positive effector of the carboxylase.
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PMID:Regulation of acetyl-coA carboxylase: properties of coA activation of acetyl-coA carboxylase. 610 89

Among more than 7000 mutants of Saccharomyces cerevisiae, requiring saturated fatty acids, 61 acetyl-CoA-carboxylase-deficient strains have been identified. According to their mutual complementation characteristics these mutants have been assigned to two different genes, acc1 and acc2. Both acetyl-CoA carboxylase genes are unlinked to each other and to the fatty acids synthetase genes fas1 and fas2. The acetyl-CoA carboxylases of several acc1 and acc2 mutants have been purified and assayed for their overall and component enzyme activities. Besides overall acetyl-CoA carboxylation, which was lost in all cases, both component enzymes, biotin carboxylase and transcarboxylase, were simultaneously affected in most mutants, though often to a different relative extent. Similarly, the comparison of biochemical and genetic complementation data revealed no basis for a clear distinction between specific biotin carboxylase and transcarboxylase mutants. These results suggest that acc1 is a cluster gene coding for a multifunctional protein harboring both acetyl-CoA carboxylase component enzyme activities on the same polypeptide chain. The acetyl-CoA carboxylase isolated from acc2 mutants was free of biotin. Correspondingly, biotin:apoacetyl-CoA-carboxylase ligase activity was missing in acc2 mutants. Therefore, it is concluced that the primary defect in acc2 mutants is in the biotin:apocarboxylase ligase. In agreement with this conclusion, the acc2 acetyl-CoA carboxylase can be activated, in the presence of biotin and ATP, by ligase preparations from wild-type or acc1 mutant cells. By the use of these mutants, evidence was obtained that in vivo the biotinylation of both acetyl-CoA carboxylase and pyruvate carboxylase is catalyzed by the same ligase.
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PMID:Yeast mutants defective in acetyl-coenzyme A carboxylase and biotin: apocarboxylase ligase. 610 18

Acetyl-CoA carboxylase is activated by physiological concentrations of CoA. Activation of partially purified enzyme by CoA is accompanied by a decrease in the Km for acetyl-CoA from 0.2 mM to about 4 microM, which is the physiological concentration of acetyl-CoA in the cytosol. CoA activation of the purified enzyme is accompanied by an increase in the Vmax, without changing the Km for acetyl-CoA. The Km for acetyl-CoA of the purified enzyme is about 10 to 40 microM. The purification procedure results in a decrease in the Km for acetyl-CoA; under these conditions, CoA activation does not cause further lowering of the Km. CoA activation is accompanied by polymerization of the enzyme. However, CoA activation is not causally related to polymerization. There is one CoA binding site/subunit of acetyl-CoA carboxylase. CoA binding at that site is not affected by the presence of citrate, but palmityl-CoA inhibits CoA binding. CoA alone cannot reverse palmityl-CoA inhibition of the carboxylase. Bovine serum albumin and CoA together can activate the palmityl-CoA-inhibited enzyme. This indicates that the involvement of bovine serum albumin-like protein, CoA, and palmityl-CoA may play a physiologically significant role in the control of acetyl-CoA carboxylase.
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PMID:Coenzyme A activation of acetyl-CoA carboxylase. 610 27

Administration of estradiol-17 beta to male Xenopus laevis evokes the proliferation of the endoplasmic reticulum and the Golgi apparatus and the synthesis and secretion by the liver of massive amounts of the egg yolk precursor phospholipoglycoprotein, vitellogenin. We have investigated the effects of estrogen on three key regulatory enzymes in lipid biosynthesis, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, the major regulatory enzyme in cholesterol and isoprenoid synthesis, and acetyl-CoA carboxylase and fatty acid synthetase, which regulate fatty acid biosynthesis. HMG-CoA reductase activity and cholesterol synthesis increase in parallel following estrogen administration. Reductase activity in estrogen stimulated Xenopus liver cells peaks at 40-100 times the activity observed in control liver cells. The increased rate of reduction of HMG-CoA to mevalonic acid is not due to activation of pre-existing HMG-CoA reductase by dephosphorylation, as the fold induction is unchanged when reductase from control and estrogen-stimulated animals is fully activated prior to assay. The estrogen-induced increase of fatty acid synthesis is paralleled by a 16- to 20-fold increase of acetyl-CoA carboxylase activity, indicating that estrogen regulates fatty acid synthesis at the level of acetyl-CoA carboxylase. Fatty acid synthetase activity was unchanged during the induction of fatty acid biosynthesis by estrogen. The induction of HMG-CoA reductase and of acetyl-CoA carboxylase by estradiol-17 beta provides a useful model for regulation of these enzymes by steroid hormones.
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PMID:Estrogen regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and acetyl-CoA carboxylase in xenopus laevis. 611 Jun 64

1. The effect of varying dietary levels of casein (40-140 g/kg) on hepatic lipogenesis and the levels of hepatic fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PD), malic enzyme (EC 1.1.1.40; ME), citrate cleavage enzyme (EC 4.1.3.8; CCE), acetyl CoA carboxylase (EC 6.4.1.2; AcCx), glucokinase (EC 2.7.1.2; GK), and pyruvate dehydrogenase (PDH) was examined in young, growing rats. 2. The activities of AcCx, FAS, G6PD and in vivo fatty acid synthesis were generally found to increase with increased dietary protein. 3. The levels of GK and PDH were not related to dietary protein. 4. ME decreased with increasing dietary protein. 5. The results demonstrate a dissociation between hepatic fatty acid synthesis and ME and suggest that when rats consume low-protein diets the NADPH needed for fatty acid synthesis is generated primarily by ME but that as the level of dietary protein is increased the contribution of ME is reduced while that of the phosphogluconate pathway becomes more important.
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PMID:The role of dietary protein in hepatic lipogenesis in the young rat. 611 2

The activity of 3-hydrosy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and the rate of mevalonic acid (MVA) synthesis from [I-14C]acetyl-CoA and [2-14C]malonyl-CoA in the soluble (X140000 g) and microsomal fractions of rat liver and in a reconstituted system containing the soluble and microsomal fractions were studied. The changes in the activity of HMG-CoA reductase and the rate of MVA biosynthesis in the fractions at different times of the day were analyzed. The daily rhythms of the rate of acetyl-CoA and malonyl-CoA incorporation into squalene, sterols and fatty acids in the postmitochondrial fraction and the daily changes in the acetyl-CoA carboxylase activity of the soluble fraction of rat liver were compared. The incorporation of labelled acetyl-CoA and malonyl-CoA into MVA showed that the latter can be synthesized from these two substrates both in the soluble and microsomal fractions. Malonyl-CoA is a preferable substrate for MVA synthesis in the soluble fraction. MVA synthesis from acetyl-CoA proceeds fastr in the intact and solubilized microsomes than in the soluble fraction. The activity of HMG-CoA reductase was found in the soluble and microsomal fractions in practically equal amounts. The enzyme activity was increased in the microsomal fraction after its solubilization. The rate of MVA biosynthesis from acetyl-CoA and the activity of HMG-CoA reductase in the soluble fraction are practically unaffected by day-to-night changes. The activity of HMG-CoA reductase and MVA biosynthesis from acetyl-CoA in the intact and solubilized microsomal fractions reached their maximal values in the middle of the dark period. The rate of MVA biosynthesis from malonyl-CoA was decreased in the middle of the dark period in all fractions studied and reached its maximum in the middle of the light period. The daily rhythms of the acetyl-CoA carboxylase activity in the soluble fraction and the rate of MVA biosynthesis from malonyl-CoA in all fractions show a coincidence. a comparison of incorporation by the postmitochondrial fractions of acetyl-CoA and malonyl-CoA into the total non-saponified lipid fraction and its components, e. g. squalene, lanosterol and cholesterol, as well as into sterols precipitated by digitonin, showed that malonyl-CoA incorporation into the total non-saponified lipid fraction was more intensive than that of acetyl-CoA. However, acetyl-CoA was far more efficiently incorporated into sterols precipitated by digitonin or isolated by TLC than malonyl-CoA. The rate of acetyl-CoA incorporation into the total non-saponified lipid fraction and into squalene, lanosterol and cholesterol was maximal in the middle of the dark period and minimal in the middle of the light period. On the contrary, the rate of malonyl-CoA incorporation into these products was minimal in the middle of the dark period and maximal in the middle of the light period. The rate of fatty acid biosynthesis from acetyl-CoA was increased in the middle of the light and dark periods...
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PMID:[Activities of 3-hydroxy-3-methylglutaryl-CoA reductase and acetyl-CoA carboxylase and rate of biosynthesis of mevalonic acid, squalene, sterols and fatty acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in rat liver: changes induced by daily rhythm]. 611 51

A protein kinase which phosphorylates and inactivates acetyl-CoA carboxylase has been purified to apparent homogeneity from rat liver. The kinase was found to exist in two forms: bound to carboxylase in a complex or in a free form that is in different stages of aggregation over a wide range of molecular weights. The purification of the kinase involved first partial purification of acetyl-CoA carboxylase through polyethylene glycol precipitation and DEAE-cellulose chromatography. The kinase was then separated from acetyl-CoA carboxylase by Sepharose 2B chromatography. The molecular weight of the kinase subunit was 170,000 as determined by sodium dodecyl sulfate-gel electrophoresis. The incorporation of 1 mol of phosphate/mole of carboxylase subunit caused complete inactivation of the carboxylase. Acetyl-CoA carboxylase, inactivated by the kinase, can be dephosphorylated and reactivated when incubated with phosphorylase phosphatase. The Km values of the kinase for acetyl-CoA carboxylase and ATP are 90 nM and 20 microM, respectively. The kinase was found to be cyclic AMP-independent, but activated by CoA. The protein kinase can phosphorylate acetyl-CoA carboxylase, protamine, and histones, but could not act on hydroxymethylglutaryl-CoA reductase or phosphorylase b.
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PMID:Purification and properties of a kinase which phosphorylates and inactivates acetyl-CoA carboxylase. 612 Jan 70


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