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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)

Acetyl coenzyme A (CoA) carboxylase (EC 6.4.1.2), an enzyme catalyzing the synthesis of malonyl-CoA, was cytochemically localized in endoplasmic reticulum (ER) of sclerotia-like cells of submerged Claviceps purpurea Tul. producing clavine alkaloids. The enzymic activity was structurally bound in unit membranes of ER strands which, later on, evolved into vacuoles containing lipoprotein material. The reaction product was absent from ER in nonvacuolized filamentous hyphae and ovoid asexual spores containing numerous lipid globules; it was also absent from ER in the mycelium of submerged C. purpurea strain producing no alkaloids. In view of our previous morphogenetic observations and the available biochemical evidence, the observed localization of acetyl-CoA carboxylase was assumed not to coincide with fatty acid biosynthesis but to represent sites of alkaloid synthesis.
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PMID:Fine structural localization of alkaloid synthesis in endoplasmic reticulum of submerged Claviceps purpurea. 2 85

The effects of citrate and cyclic AMP on the rate and degree of phosphorylation and inactivation of rat liver acetyl-CoA carboxylase were examined. High citrate concentrations (10 to 20 mM), which are generally used to stabilize and activate the enzyme, inhibit phosphorylation and inactivation of carboxylase. At lower concentrations of citrate, the rate and degree of phosphorylation are increased. Furthermore, phosphorylation and enzyme inactivation are affected by cyclic AMP under these conditions. At high citrate concentrations, cyclic AMP has little or no effect on inactivation and phosphorylation of acetyl-CoA carboxylase. Phosphorlation and inactivation of carboxylase is accompanied by depolymerization of the polymeric form of the enzyme into intermediate and protomeric forms. Depolymerization of carboxylase requires the transfer of the gamma-phosphate group from ATP to carboxylase. Inactivation occurs in the absence of CO2, which indicates that phosphorylation of the enzyme is the cause of inactivation and depolymerization, i.e. carboxylation of the enzyme is not responsible for inactivation of the enzyme.
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PMID:Regulation of rat liver acetyl-CoA carboxylase. Stimulation of phosphorylation and subsequent inactivation of liver acetyl-CoA carboxylase by cyclic 3':5'-monophosphate and effect on the structure of the enzyme. 3 Jul 74

If acetyl-CoA carboxylase in epididymal fat tissue is subject to control by convalent modification as in the case of the liver enzyme, catalytically different forms of carboxylase should exist, independent of polymerization. By treating epididymal fat tissue in culture with epinephrine, we have demonstrated catalytically less active forms of acetyl-CoA carboxylase. The catalytically less active forms of the enzyme reacted to antibody with the same efficiency as the active form of carboxylase. However, the less active enzyme formed by epinephrine treatment of tissues has a sedimentation constant of 30 to 35 S, whereas that of the enzyme from control tissue is 45 S. Incubation of the less active forms of the carboxylase with 10 mM citrate and up to 10 mg/ml of bovine serum albumin activated the enzyme without any change in the sedimentation constant. Therefore, the less active forms of the carboxylase formed as a result of epinephrine treatment are not due to the depolymerization of polymeric forms (45 S) to the protomeric forms (17 to 20 S), but to the formation of intermediate species of carboxylase which cannot form polymeric enzyme (45 S) in the presence of high concentrations of citrate.
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PMID:Effect of epinephrine on acetyl-CoA carboxylase in rat epididymal fat tissue. 3 Jul 75

1. Rapid effects of hormones on glycogen metabolism and fatty acid synthesis in the perfused liver of the mouse were studied. 2. In perfusions lasting 2h, of livers from normal mice, glucagon in successive doses, each producing concentrations of 10(-10) or 10(-9)M, inhibited fatty acid and cholesterol synthesis. In perfusions lasting 40--50 min, in which medium was not recycled, inhibition of fatty acid synthesis was only observed with glucagon at concentrations greater than 10(-9)M. This concentration was about two orders of magnitude higher than that required for the stimulation of glycogen breakdown. Glucagon did not inhibit the activity of acetyl-CoA carboxylase, assayed 10 or 20 min after addition of glucagon (10(-9) or 10(-10)M). It is proposed that the action of glucagon on hepatic fatty acid biosynthesis could be secondary in time to depletion of glycogen. Insulin prevented the effect of glucagon (10(-10)M) on glycogenolysis, but not that of vasopressin. 3. Livers of genetically obese (ob/ob) mice did not show significant inhibition of lipid biosynthesis in response to glucagon, although there was normal acceleration of glycogen breakdown. This resistance to glucagon action was not reversed by food deprivation. Livers of obese mice exhibited resistance to the counteraction by insulin of glucagon-stimulated glycogenolysis, which was reversible by partial food deprivation.
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PMID:Effects of glucagon and insulin on fatty acid synthesis and glycogen degradation in the perfused liver of normal and genetically obese (ob/ob) mice. 3 66

Fatty acid synthetase was purified 13-fold from lactating rabbit mammary glands by a procedure which involved chromatography on DEAE-cellulose, ammonium sulphate precipitation and gel filtration on Sepharose 4B. The preparation was completed within two days and over 100 mg of enzyme was isolated from 100--150 g of mammary tissue, which represented a yield of over 40%. The preparation was homogeneous by the criteria of polyacrylamide gel electrophoresis and ultracentrifugal analysis. The sedimentation constant, S20,w was 13.3 S, the absorption coefficient, A280nm1%, measured refractometrically was 10.0 +/- 0.1, and the amino acid composition was determined. The subunit molecular weight determined by gel electrophoresis in the presence of sodium dodecyl sulphate was 252,000 +/- 6,000, and the molecular weight of the native enzyme measured by sedimentation equilibrium was 515,000. These experiments indicate that at the concentrations which exist in mammary tissue (2--4 mg/ml) fatty acid synthetase is a dimer. The purified enzyme did however show a tendency to dissociate to a monomeric 9-9S species on storage for several days or following exposure to a low ionic strength buffer at pH 8.3. There was only a small quantity of alkali labile phosphate (0.2 molecules per subunit) bound covalently to the purified enzyme. Acetyl-CoA carboxylase was purified 300-fold in a 50% yield within 24 h by ammonium sulphate and polyethylene glycol precipitations [Hardie, D.G. and Cohen, P. (1978) FEBS Lett. 91, 1--7]. The preparation was in a state approaching homogeneity as judged by polyacrylamide gel electrophoresis, gel filtration on Sepharose 4B and ultracentrifugal analysis. The sedimentation constant, S20,w, was 50.5 S, the absorption index, A280nm1%, was 14.5 +/- 0.7, and the amino acid composition was determined. The subunit molecular weight of acetyl-CoA carboxylase determined by gel electrophoresis in the presence of sodium dodecyl sulphate was identical to that of fatty acid synthetase (252,000) as shown by electrophoresis of a mixture of the two proteins. The preparations also contained two minor components of molecular weight 235,000 and 225,000, which appear to be derived from the major species of mol. wt 252,000. A large emount of phosphate (3.2 molecules per subunit) was found to be bound covalently to the purified enzyme. The properties of fatty acid synthetase and acetyl-CoA carboxylase are compared to those obtained by other workers.
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PMID:Purification and physicochemical properties of fatty acid synthetase and acetyl-CoA carboxylase from lactating rabbit mammary gland. 3 36

When Mycobacterium convolutum R22 was grown on the n-alkanes C13 through C16, the predominant fatty acids were of the same chain length as the growth substrate. Cells grown on C13 through C16 n-alkanes incorporated between 15 and 85 pmol of acetate per microgram of lipid into the fatty acids, whereas acetate- or propane-grown cells incorporated 280 and 255 pmol of acetate per microgram of lipid, respectively. In vivo experiments demonstrated that hexadecane, hexadecanoic acid, and hexadecanoylcoenzyme A (CoA) all inhibited de novo fatty acid synthesis. Hexadecanoyl-CoA was the most potent inhibitor. Hexadecane and hexadecanoic acid inhibited acetyl-CoA carboxylase by up to 37 and 39%, respectively, at 1 mM. Hexadecanoyl-CoA inhibited the enzyme activity by 65% at 50 micrometer. Cells that were grown on C14 through C16 n-alkanes had about 25 times less acetyl-CoA carboxylase activity than did cells grown on acetate or propane, suggesting repressed levels of the enzyme. Hexadecane- or pentadecane-grown cells were found to have 5 to 10 times more intracellular free fatty acid than cells grown on acetate, propane, or ethane.
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PMID:Regulation of fatty acid biosynthesis by hydrocarbon substrates in Mycobacterium convolutum. 3 51

A hormonally induced change in the covalent phosphorylation state of several enzymes is generally regarded as an important mechanism for hormonal modulation of enzyme activity. We have previously demonstrated that epinephrine stimulates the phosphorylation of a peptide of Mr = 220,000 in adipocytes. Incubation of 32P-labeled cytosolic proteins from adipocytes and hepatocytes with antisera raised against homogeneous chicken and rat liver acetyl coenzyme A carboxylase results in the specific and complete precipitation of the same phosphopeptide. No other major phosphopeptide is specifically precipitated. In hepatocytes, glucagon stimulates the incorporation of 32P into this peptide associated with an inhibition of enzyme activity. These data, coupled with previous studies in adipocytes, suggest that cyclic AMP-dependent protein phosphorylation plays a major role in the regulation of acetyl-CoA carboxylase activity and of fatty acid biosynthesis in adipose tissue and liver.
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PMID:Glucagon regulation of protein phosphorylation. Identification of acetyl coenzyme A carboxylase as a substrate. 3 66

Intraperitoneal injection of inorganic 32P into rats results in the incorporation of 32P into acetyl-CoA carboxylase without inactivation of the enzyme. Administration of epinephrine stimulates 32P incorporation and results in enzyme inactivation. Incubation of epididymal fat tissues with inorganic 32P also results in incorporation of 32P into carboxylase. This 32P incorporation reaches a maximum level in 3 h and it has no effect on carboxylase activity. Administration of epinephrine at the time of maximum phosphorylation (3 h) results in further phosphorylation and inactivation of carboxylase. Propranolol, a beta-adrenergic blocking agent which inhibits epinephrine action, blocks both the epinephrine-stimulated phosphorylation and the inactivation of the carboxylase. However, propranolol has no effect on that component of the phosphorylation which is unrelated to enzyme inactivation. These results establish that phosphorylation of carboxylase occurs in vivo at two different sites, only one of which results in enzyme inactivation. The phosphorylation site associated with enzyme inactivation is hormonally controlled.
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PMID:Stimulation by epinephrine of in vivo phosphorylation and inactivation of acetyl coenzyme A carboxylase of rat epididymal adipose tissue. 3 89

The rate of in vivo fatty acid synthesis as well as the levels of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme (ME), citrate cleavage enzyme (CCE), acetyl-CoA carboxylase (ACX) and fatty acid synthetase (FAS) activities, have been studied in the liver of rats fed a fat-free diet for 7 days, followed by diets containing different amounts of soybean oil (0 to 24.79 kcal%) for 7 days. The dietary fat depressed activities of G6PD, 6PGD, ME, CCE, and FAS significantly at 1.24 or 2.48 kcal%. On the other hand, AC activity and the rate of fatty acid synthesis were decreased when the level of dietary fat was 12.39 kcal% or greater. These findings, as well as the pattern of decrement of enzyme activities and of lipogenesis, suggest a close correlation of fat feeding to ACX activity and fatty acid synthesis. The results also suggest that changes of G6PD, 6PGD, ME, CCE, and FAS activities may be largely independent of those modifications which occur in the substrate flux, concomitantly with the decrease of lipogenesis caused by the inclusion of fat in the diet.
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PMID:Response of rat hepatic fatty acid synthesis and activities of related enzymes to changes in level of dietary fat. 3 77

In 5 French Alpine goats, omental adipose tissue acetyl-CoA carboxylase, glucose-6-phosphate deshydrogenase, malic enzyme and lipoprotein lipase activities significantly decreased during the third month of gestation, whereas plasma non-esterified fatty acid and triacyglycerol contents increased. This probably reflects an early decreasing rate of adipose tissue anabolism during gestation in the Goat. At the third week of lactation, anabolic activities relative to DNA content of adipose tissue were extremely low, and the tissue weight relative to DNA was lower than during gestation. Metabolic alterations of omental adipose tissue in early lactation do not seem to be related to milk production level. These results could contribute to a better control of the kinetic of body lipid stores during the reproductive cycle in high milk yielding ruminants.
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PMID:[Metabolic activity of adipose tissue in the goat during gestation and at the beginning of lactation]. 3 15


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