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)

1. Epididymal adipose tissues obtained from rats that had been previously starved, starved and refed a high fat diet for 72h, starved and refed bread for 144h or fed a normal diet were incubated in the presence of insulin+glucose or insulin+glucose+acetate. 2. Measurements were made of the whole-tissue concentrations of hexose phosphates, triose phosphates, glycerol 1-phosphate, 3-phosphoglycerate, 6-phosphogluconate, adenine nucleotides, acid-soluble CoA, long-chain fatty acyl-CoA, malate and citrate after 1h of incubation. The release of lactate, pyruvate and glycerol into the incubation medium during this period was also determined. 3. The rates of metabolism of glucose in the hexose monophosphate pathway, the glycolytic pathway, the citric acid cycle and into glyceride glycerol, fatty acids and lactate+pyruvate were also determined over a 2h period in similarly treated tissues. The metabolism of acetate to CO(2) and fatty acids in the presence of glucose was also measured. 4. The activities of acetyl-CoA carboxylase, fatty acid synthetase and isocitrate dehydrogenase were determined in adipose tissues from starved, starved and fat-refed, and alloxan-diabetic animals and also in tissues from animals that had been starved and refed bread for up to 96h. Changes in these activities were compared with the ability of similar tissues to incorporate [(14)C]glucose into fatty acids in vitro. 5. The activities of acetyl-CoA carboxylase and fatty acid synthetase roughly paralleled the ability of tissues to incorporate glucose into fatty acids. 6. Rates of triglyceride synthesis and fatty acid synthesis could not be correlated with tissue concentrations of long-chain fatty acyl-CoA, citrate or glycerol 1-phosphate. In some cases changes in phosphofructokinase flux rates could be correlated with changes in citrate concentration. 7. The main lesion in fatty acid synthesis in tissues from starved, starved and fat-refed, and alloxan-diabetic rats appeared to reside at the level of pyruvate utilization and to be related to the rate of endogenous lipolysis. 8. It is suggested that pyruvate utilization by the tissue may be regulated by the metabolism of fatty acids within the tissue. The significance of this in directing glucose utilization away from fatty acid synthesis and into glyceride-glycerol synthesis is discussed.
Biochem J 1970 Sep
PMID:The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions. 424 59

The total cytosol activity of acetyl-CoA carboxylase (acetyl-CoA:CO(2) ligase (ADP), EC 6.4.1.2) in the liver is known to be 6- to 10-fold higher in genetically obese hyperglycemic mice (C57BL/6J-ob) than in nonobese mice. The results of immunochemical titrations, Ouchterlony double-diffusion analysis, and kinetic and heat inactivation studies indicated that this rise in the level of carboxylase activity in liver extracts from obese mice was ascribed to an increase in the quantity of the enzyme protein, which was indistinguishable from that derived from nonobese mice. Combined immunochemical and isotopic techniques showed that the rate of synthesis of the carboxylase per liver was 7.7-fold higher in obese than in nonobese mice. The rate of degradation of the carboxylase was found to be 1.7-fold lower in obese than in nonobese mice, the half-life being 115 and 67 hr, respectively. These results indicate that the increase in the acetyl-CoA carboxylase content of the liver in obese mice is due mainly to a rise in the rate of enzyme synthesis, and in a minor degree, to a decrease in the rate of enzyme degradation.
Proc Natl Acad Sci U S A 1971 Sep
PMID:Synthesis and degradation of liver acetyl coenzyme A carboxylase in genetically obese mice. 500 32

Isolated rat hepatocytes, previously shown to display enhanced rates of fatty acid biosynthesis upon a brief exposure to insulin, were used to study acute effects of this hormone on other aspects of hepatic fatty acid metabolism. Insulin activates the incorporation of exogenously added fatty acids into glycerolipids and depresses their utilization in the formation of ketone bodies. Insulin increases both the activity of acetyl-CoA carboxylase and the cellular content of malonyl-CoA. Evidence is presented that malonyl-CoA plays an important role in the insulin-mediated control of both ketogenesis and de novo fatty acid synthesis. All metabolic parameters studied are affected by glucagon in a manner opposite to that of insulin.
Horm Metab Res 1980 Sep
PMID:Acute effects of insulin on fatty acid metabolism in isolated rat hepatocytes. 610 68

Acetyl-CoA carboxylase has been purified from lactating rat mammary gland using a combination of ammonium sulphate and poly(ethyleneglycol) precipitations. The enzyme was purified from 35--70-fold with a yield of over 50%, the exact figures being difficult to estimate because of activation of the enzyme that occurs during the preparation. The preparation was homogeneous by the criterion of polyacrylamide gel electrophoresis in sodium dodecyl sulphate and had a single subunit of molecular weight 240,000, containing 1.02 +/- 0.04 molecules of biotin and 3.1 +/- 1.7 molecules of alkali-labile phosphate per subunit. The purified enzyme was phosphorylated and inactivated rapidly when incubated in the presence of [gamma 32P]ATP and magnesium ions with the purified catalytic subunit of cyclic-AMP-dependent protein kinase from rabbit skeletal muscle. Both phosphorylation and inactivation are blocked by the heat-stable protein inhibitor of cyclic-AMP-dependent protein kinase, and can be reversed by incubation with purified protein phosphatase-1 from rabbit skeletal muscle. The inactivation by the protein kinase and reactivation by the protein phosphatase correlate with the near-stoichiometric phosphorylation and dephosphorylation of site(s) located in a single tryptic peptide. Phosphorylation does not affect the Km for substrates, but brings about a twofold decrease in V and a twofold increase in the apparent dissociation constant for the allosteric activator, citrate. We also present evidence that the activation of rabbit mammary acetyl-CoA carboxylase by protein phosphatase-1 described previously [Hardie and Cohen (1979) FEBS Lett. 103, 333-338] is due to dephosphorylation at site(s) which are not phosphorylated by either cyclic-AMP-dependent protein kinase or acetyl-CoA carboxylase kinase-2. These results suggest that the rapid inactivation of acetyl-CoA carboxylase, and hence fatty acid synthesis, by adrenaline in adipose tissue, or glucagon in the liver, is due to phosphorylation of the enzyme by cyclic-AMP-dependent protein kinase.
Eur J Biochem 1980 Sep
PMID:Reversible phosphorylation and inactivation of acetyl-CoA carboxylase from lactating rat mammary gland by cyclic AMP-dependent protein kinase. 610 9

When 1-, 2- and 9-month-old rats previously adapted to a commercial stock diet were fed a fat-free diet (induction) and also when the process was reversed (repression), the turnovers of lipogenic enzymes in liver were measured by following time courses for the change of the enzyme activities. The magnitudes of the induction of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were very high in 1-month-old rats and then decreased with aging. In the induction phase, the rates of synthesis of the enzymes were markedly decreased with increasing age as compared with the rate constants of degradation. The age-dependent alterations were not shown so much in the repression phase as in the induction phase. It is suggested that the age-dependent impairment in induction may be due to some alterations in the enzyme-forming system.
Biochim Biophys Acta 1981 Sep 24
PMID:Age-dependent modifications of lipogenic enzymes. 611 23

The effect of vasopressin on the short-term regulation of fatty acid synthesis was studied in isolated hepatocytes from rats fed ad libitum. Vasopressin stimulates fatty acid synthesis by 30-110%. This increase is comparable with that obtained with insulin. Angiotensin also stimulates fatty acid synthesis, whereas phenylephrine does not. The dose-response curve for vasopressin-stimulated lipogenesis is similar to the dose-response curve for glycogenolysis and release of lactate plus pyruvate. Vasopression also stimulates acetyl-CoA carboxylase activity in a dose-dependent manner. Vasopressin does not relieve glucagon-inhibited lipogenesis, whereas insulin does. The action of vasopressin on hepatic lipogenesis is decreased, but not suppressed, in Ca2+-depleted hepatocytes. The results suggest that vasopressin acts on lipogenesis by increasing availability of lipogenic substrate (lactate + pyruvate) and by activating acetyl-CoA carboxylase.
Biochem J 1981 Sep 15
PMID:Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin. 611 87

The zonal distribution of cytosolic acetyl-CoA carboxylase, mitochondrial 3-hydroxyacyl-CoA dehydrogenase and 3-hydroxybutyrate dehydrogenase was studied in microdissected liver tissue. In fed male and female rats the activity of the lipogenic enzyme acetyl-CoA carboxylase was 1.6-times higher in the perivenous than in the periportal zone of the liver acinus. 3-Hydroxybutyrate dehydrogenase, which is involved in the formation of the ketone body, 3-hydroxybutyrate, exhibited a similar distribution pattern with a 1.5-1.8-times higher activity in the perivenous than in the periportal zone. In contrast, the activity of 3-hydroxyacyl-CoA dehydrogenase, the third enzyme in beta-oxidation, was about equally distributed between the periportal and the perivenous zone of the liver acinus. The results indicate a predominance of lipogenesis in the perivenous, mainly glycolytic zone of the liver acinus. Furthermore, these data support the hypothesis that beta-oxidation supplies energy for basic and anabolic processes like gluconeogenesis in the periportal zone, while it provides acetyl-CoA for ketogenesis besides energy for basic needs in the perivenous zone.
Eur J Biochem 1983 Sep 01
PMID:Distribution of enzymes of fatty acid and ketone body metabolism in periportal and perivenous rat-liver tissue. 613 5

Acetyl-coenzyme A carboxylase has been purified from the plastids of developing castor oil seeds. High concentrations of the enzyme are required for stability as well as the presence of dithiothreitol, glycerol, bicarbonate, Triton X-100, and polyvinyl-pyrrolidone. It has a molecular weight of approximately 528,000 and appears to be membrane associated. Acetyl-CoA carboxylase is active over a wide pH range with an optimum at 8.0. Arrhenius plots are biphasic. The enzyme displays normal Michaelis-Menten kinetics with limiting Michaelis constants of KATP, 0.1 mM; KHCO-3, 3.0 mM; and Kacetyl-CoA, 0.05 mM. Monovalent cations, such as K+ and Cs+, exert a small activating effect on the enzyme while a divalent cation, Mn2+ or Mg2+, is essential for activity. The enzyme does not appear to be highly regulated by cellular metabolites.
Arch Biochem Biophys 1983 Sep
PMID:Acetyl-coenzyme A carboxylase from the developing endosperm of Ricinus communis. I. Isolation and characterization. 613 95

Rat mammary gland acetyl-CoA carboxylase (acetyl-CoA:carbon dioxide ligase (ADP forming), EC 6.4.1.2) is rapidly and irreversibly inactivated by micromolar concentrations of S-(4-bromo-2,3-dioxobutyl)-CoA (BDB-CoA) or p-hydroxymercuribenzoate (PHMB). Inhibition of both half reactions (i.e., the biotin carboxylation and the carboxyltransferase) catalyzed by acetyl-CoA carboxylase closely parallels loss in overall activity (malonyl-CoA synthesis). The presence of a substrate or product (acetyl-CoA, ATP, ADP, Pi) or inhibitor (palmitoyl-CoA) does not protect the enzyme from inhibition caused by BDB-CoA or PHMB. On the other hand, citrate, an activator of acetyl-CoA carboxylase, affords substantial protection against inhibition by BDB-CoA and PHMB. Covalent modification by BDB-CoA or PHMB appears to lock acetyl-CoA carboxylase in an inactive conformation (15-30 S) that is unable to undergo citrate-induced self-association into the catalytically competent polymeric form.
Biochim Biophys Acta 1984 Sep 11
PMID:Inhibitory effects of sulfhydryl reagents on acetyl-CoA carboxylase from rat mammary gland. 614 6

Acetyl-CoA carboxylase was purified 300-fold from rat liver, in the absence of added citrate, by precipitation from an 18,000g supernatant in the presence of Triton X-100 at 105,000g and 20 degrees C, followed by chromatography on phosphocellulose. Acetyl-CoA carboxylase activity in this preparation was activated by preincubation with GTP (0.1-2.0 mM) and with citrate (20 mM). Colchicine (10(-6)-10(-3) M) inhibited enzyme activity and counteracted the effects of GTP and citrate. Sucrose density gradient centrifugation demonstrated that GTP and citrate preincubation promoted the formation of the polymeric, active enzyme, while colchicine engendered disassembly. Preincubation of the purified acetyl-CoA carboxylase at 4 degrees C caused inactivation and disassembly, which was countered by preincubation at 37 degrees C in the presence of GTP or citrate. These results suggest that GTP, like citrate, activates acetyl-CoA carboxylase by enhancing the conversion of the protomeric form of the enzyme to its more active, polymeric state.
Arch Biochem Biophys 1984 Sep
PMID:Guanosine triphosphate and colchicine affect the activity and the polymeric state of acetyl-CoA carboxylase. 614 16


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