Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Changes in the activities of acetyl-CoA carboxylase and HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase were studied in primary cultures of adult-rat hepatocytes after exposure of the cells to insulin and/or carbohydrates. To determine the contribution of protein synthesis to changes in enzyme activity, the relative rate of synthesis of each enzyme was measured and the amount of translatable mRNA coding for the enzymes was determined by translation in vitro and immunoprecipitation. Addition of insulin to the culture medium increased the activities of acetyl-CoA carboxylase and HMG-CoA reductase by approx. 4- and 3-fold respectively. Although similar increases in the relative rate of synthesis of each protein and template activity were noted, initial increases in the activity of each enzyme occurred before any changes in protein synthesis were observed, suggesting the involvement of post-translational modification of enzyme activity in addition to changes in protein synthesis. The addition of fructose to the culture medium, in the absence of insulin, increased the activity of the carboxylase and the reductase approx. 3-fold, similar to the effects of insulin. However, the effect of fructose was to increase the rate of synthesis and the amount of translatable mRNA coding for acetyl-CoA carboxylase, whereas the increase in the activity of HMG-CoA reductase was not accompanied by any changes in the rate of synthesis or template activity. The effects of fructose could not be mimicked by glucose unless insulin was also present in the culture medium. Similar to observations in vitro, the injection of insulin or the feeding of a high-fructose diet to rats made diabetic by the injection of streptozotocin produced an increase in the activities of acetyl-CoA carboxylase and HMG-CoA reductase, and only the increase in the activity of the carboxylase was accompanied by an increase in the amount of translatable mRNA coding for the enzyme. The results are discussed in terms of the effects of fructose on the synthesis of enzymes involved in lipogenesis.
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PMID:Role of protein synthesis in the carbohydrate-induced changes in the activities of acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase in cultured rat hepatocytes. 286 Aug 99

Primary cultures of adult rat hepatocytes were utilized to ascertain the impact of free fatty acids on the insulin plus dexamethasone induction of acetyl-CoA carboxylase. Lipogenesis was induced threefold by the combination of insulin and dexamethasone. The rise in fatty acid synthesis was accompanied by a comparable increase in the rate-determining enzyme acetyl-CoA carboxylase. Dexamethasone was required for the insulin induction of acetyl-CoA carboxylase. Under the permissive action of glucocorticoid, 10(-7) M insulin maximally increased enzyme activity. Half-maximum stimulation occurred with 5 X 10(-9) M insulin. Media containing 0.2 mM palmitate, oleate, linoleate, arachidonate, or docosahexaenoate significantly suppressed the hormonal induction of acetyl-CoA carboxylase. The extent of suppression was only 30-35% and did not vary with chain length or degree of unsaturation. Carboxylase activity was not suppressed further by raising the concentration of linoleate to 0.5 mM; however, 0.5 mM palmitate depleted the cells of ATP and abolished acetyl-CoA carboxylase activity. Therefore, based upon the inhibitory characteristics of the various fatty acids and the lack of a concentration dependency of the fatty acid inhibition, it would appear that fatty acid inhibition of the induction of acetyl-CoA carboxylase activity may not be a direct, physiological regulatory mechanism.
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PMID:Fatty acid inhibition of hormonal induction of acetyl-coenzyme A carboxylase in hepatocyte monolayers. 287 Jun 83

Epidermal growth factor (EGF) stimulates lipogenesis by 3-4-fold in isolated adipocytes, with a half-maximal effect at 10 nM-EGF. In the same batches of cells insulin stimulated lipogenesis by 15-fold. Freezing and prolonged homogenization of adipocytes results in release of large quantities of pyruvate carboxylase from broken mitochondria, and sufficient pyruvate can be carried through into assays for this enzyme to cause significant interference with assays of acetyl-CoA carboxylase in crude adipocyte extracts. This may account for the high amount of citrate-independent acetyl-CoA carboxylase activity reported to be present in adipocyte extracts in some previous publications. This problem may be eliminated by homogenizing very briefly without freezing. By using the modified homogenization procedure, EGF treatment of adipocytes was shown to produce an effect on acetyl-CoA carboxylase activity almost identical with that of insulin. Both messengers increase Vmax. without significant effect on the Ka for the allosteric activator, citrate.
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PMID:Both insulin and epidermal growth factor stimulate lipogenesis and acetyl-CoA carboxylase activity in isolated adipocytes. Importance of homogenization procedure in avoiding artefacts in acetyl-CoA carboxylase assay. 287 82

ATP-citrate lyase and acetyl-CoA carboxylase purified from lactating rat mammary gland are phosphorylated stoichiometrically by the calmodulin-dependent multiprotein kinase from rabbit skeletal muscle. The reactions are completely dependent on the presence of both Ca2+ and calmodulin. ATP-citrate lyase and acetyl-CoA carboxylase are also phosphorylated stoichiometrically by the Ca2+- and phospholipid-dependent protein kinase (protein kinase C) purified from bovine brain. Phosphorylation of these substrates is stimulated 6-fold and 40-fold respectively by Ca2+ and phosphatidylserine. The calmodulin-dependent and phospholipid-dependent protein kinases phosphorylate the same serine residue on ATP-citrate lyase that is phosphorylated by cyclic-AMP-dependent protein kinase. The sequence of the tryptic peptide containing this site on the mammary enzyme is identical with the sequence of the peptide containing the site on ATP-citrate lyase that is phosphorylated in isolated hepatocytes in response to insulin and/or glucagon. The calmodulin-dependent, phospholipid-dependent and cyclic-AMP-dependent protein kinases phosphorylate distinct sites on acetyl-CoA carboxylase. However, one of the three phosphorylated tryptic peptides derived from enzyme treated with the phospholipid-dependent kinase is identical with the major phosphopeptide (T1) derived from enzyme treated with cyclic-AMP-dependent protein kinase. Phosphorylation of acetyl-CoA carboxylase by the phospholipid-dependent protein kinase inactivates acetyl-CoA carboxylase in a similar manner to cyclic-AMP-dependent protein kinase. With either protein kinase slightly greater phosphorylation and inactivation is seen after pretreatment of acetyl-CoA carboxylase with protein phosphatase-2A, but the effects of the protein phosphatase treatment are not completely reversed. Inactivation by the phospholipid-dependent protein kinase is Ca2+- and phospholipid-dependent, is reversed by protein phosphatase-2A, and correlates with the degree of phosphorylation. The relevance of these findings to insulin- and growth-factor-promoted phosphorylation of ATP-citrate lyase and acetyl-CoA carboxylase in intact cells is discussed.
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PMID:Characterization of the phosphorylation of rat mammary ATP-citrate lyase and acetyl-CoA carboxylase by Ca2+ and calmodulin-dependent multiprotein kinase and Ca2+ and phospholipid-dependent protein kinase. 287 35

Effect of prior nutritional status of the animal on the activity of lipogenic enzymes and the fatty acid content of cultured hepatocytes was investigated. Hepatocytes were isolated from rats that were starved for 24 h ('starved') or continuously fed ('fed'), or starved for 48 h and then re-fed for 48 h ('re-fed') with a carbohydrate-rich fat-free diet, and maintained as monolayer cultures for 96 h in a serum-free glucose-rich medium (Waymouth's MB752/1) supplemented with insulin, dexamethasone and tri-iodothyronine. The fatty acid content and the activities of acetyl-CoA carboxylase, fatty acid synthase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were determined initially at 3 h after plating and then every 24 h. Initially the activities of all the four enzymes were highest in hepatocytes isolated from the re-fed rats and lowest in those from the starved rats. With time in culture, the activity of all these enzymes increased severalfold (2-5, depending on the enzyme under consideration) in hepatocytes isolated from fed and starved rats, whereas there was a severalfold (2-5) decrease in the activity of these enzymes in hepatocytes isolated from re-fed rats. The initial fatty acid content of the hepatocytes from re-fed rats was 2-3 times that in the other two groups of hepatocytes. The fatty acid content seemed to increase in all three groups of hepatocytes during the 96 h in culture, but these apparent increases were not statistically significant.
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PMID:Effect of prior nutritional status on the activity of lipogenic enzymes in primary monolayer cultures of rat hepatocytes. 287 93

Diabetic and nondiabetic rats were used to ascertain if dietary polyunsaturated fats inhibited hepatic acetyl-CoA carboxylase and fatty acid synthetase in insulin-insufficient rats as had been previously shown for normal rats. Male rats were rendered diabetic (400-600) mg glucose/100 mL blood) with streptozotocin and were fed a high fructose fat-free diet. Safflower oil or palmitate (or tallow) was added to the basal fructose diet at a level to supply 12,24 or 36% additional digestible energy. Compared with normal rats, diabetic rats had significantly lower hepatic fatty acid biosynthesis, but the proportion of acetyl-CoA carboxylase expressing catalytic activity as determined by the avidin-inactivation technique was unaffected by diabetes. Diabetes did not lower the maximal maximal activities of carboxylase and fatty acid synthetase. Moreover, the activities of these enzymes greatly exceeded the rate of fatty acid synthesis. At all levels of fat supplementation, the high linoleate safflower oil consistently resulted in a 50% lower rate of fatty acid biosynthesis than did comparable levels of tallow or palmitate. Safflower oil was also a more effective suppressor of the activities of acetyl-CoA carboxylase and fatty acid synthetase than the saturated fats. Our data suggest that the greater inhibition of hepatic fatty acid biosynthesis by polyenoic fatty acids is an insulin-independent mechanism.
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PMID:Inhibition of liver lipogenesis by dietary polyunsaturated fat in severely diabetic rats. 287 68

Activation of acetyl-CoA carboxylase during incubation of crude extracts of lactating rat mammary gland with Mg2+ and citrate can be blocked by NaF, suggesting that it represents a dephosphorylation of the enzyme. The greater extent of activation in extracts from 24 h-starved rats (200%) compared with fed controls (70%) implies that the decrease in acetyl-CoA carboxylase activity in response to 24 h starvation may involve increased phosphorylation of the enzyme. Acetyl-CoA carboxylase was purified from the mammary glands of lactating rats in the presence of protein phosphatase inhibitors by avidin-Sepharose chromatography. Starvation of the rats for 24 h increased the concentration of citrate giving half-maximal activation by 75%, and decreased the Vmax. of the purified enzyme by 73%. This was associated with an increase in the alkali-labile phosphate content from 3.3 +/- 0.2 to 4.5 +/- 0.4 mol/mol of enzyme subunit. Starvation of lactating rats for 6 h, or short-term insulin deficiency induced by streptozotocin injection, did not effect the kinetic parameters or the phosphate content of acetyl-CoA carboxylase purified from mammary glands. The effects of 24 h starvation on the kinetic parameters and phosphate content of the purified enzyme were completely reversed by re-feeding for only 2.5 h. This effect was blocked if the animals were injected with streptozotocin before re-feeding, suggesting that the increase in plasma insulin that occurs on re-feeding was responsible for the activation of the enzyme. The effects of re-feeding 24 h-starved rats on the kinetic parameters and phosphate content of acetyl-CoA carboxylase could be mimicked by treating enzyme purified from 24 h-starved rats with protein phosphatase-2A in vitro. Our results suggest that, in mammary glands of 24 h-starved lactating rats, insulin brings about a dephosphorylation of acetyl-CoA carboxylase in vivo, which may be at least partly responsible for the reactivation of mammary lipogenesis in response to re-feeding.
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PMID:The role of acetyl-CoA carboxylase phosphorylation in the control of mammary gland fatty acid synthesis during the starvation and re-feeding of lactating rats. 287 30

Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats.
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PMID:Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat. 287 33

The activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis, can be regulated by both adenine and guanine nucleotides in vitro. We have employed two inhibitors of IMP dehydrogenase, ribavarin and tiazofurin, to investigate a possible role for intracellular nucleotides in ACC regulation in rat adipocytes. Ribavarin, but not tiazofurin, leads to a profound time-dependent inhibition of ACC activity that is associated with a decrease in both intracellular ATP and GTP. This inactivating effect is largely reversed with guanosine, accompanied by increases in both ATP and GTP levels. Epinephrine-mediated inactivation of ACC in intact cells is not altered by ribavarin incubation. However, in these experiments, insulin-mediated activation is observed only after ribavarin-induced inhibition of the enzyme. These data suggest that nucleotides may modulate ACC activity and influence is regulation by insulin in intact cells. The possible mechanisms underlying the insulin activation of ACC and the role of intracellular nucleotides in insulin action are discussed.
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PMID:Modulation of acetyl-CoA carboxylase by inhibitors of IMP dehydrogenase: implications for insulin regulation. 288 May 60

Relationships between the cyclic AMP content, the rate of lipogenesis and the activity of acetyl-CoA carboxylase in acini prepared from lactating rat mammary tissue were investigated by exposing them to agents that increase their cyclic AMP content in the presence or absence of insulin. The dose-dependent inhibition of lipogenesis by theophylline in acini isolated from fed rats was highly correlated with the induced increases in acinar cyclic AMP content. Cyclic AMP of acini from 24 h-starved lactating rats was more sensitive in its response to theophylline than that in acini from fed animals. Neither forskolin nor a mixture of isoprenaline and Ro 7-2956 were able significantly to change either the rate of lipogenesis or the activity of acetyl-CoA carboxylase in acini from fed rats when added to incubations in vitro, in spite of the large increases in cyclic AMP concentration produced by these agents. Insulin was without effect on the activity of acetyl-CoA carboxylase and on either the basal or isoprenaline-stimulated cyclic AMP content of acini. These results are discussed in terms of the possibility that the rate of lipogenesis and the cyclic AMP content in mammary acini can vary independently of one another and of the activity of acetyl-CoA carboxylase.
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PMID:Modulation of intracellular cyclic AMP content and rate of lipogenesis in mammary acini in vitro. 288 37


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