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)

Metabolism of perfused livers from control and ventromedial hypothalamus (VMH)-lesioned rats has been studied. To eliminate the possibility that observed metabolic abnormalities could be realted to hyperphagia, VMH-lesioned rats were placed on restricted diet matching that of controls. Ten days postoperatively, VMH-lesioned rats had hyperinsulinemia, hypertriglyceridemia, increased blood urea nitrogen levels, together with decreased plasma free fatty acid (FFA) and glucose levels. Insulin release produced in vivo by a glucose load was much higher in VMH-lesioned than in control rats. Perfused livers from VMH-lesioned rats secreted more triglycerides and produced more urea than controls, whereas production of glucose and ketone bodies was reduced. Lipogenesis, newly synthesized triglyceride secretion, and the activity of acetyl-CoA carboxylase and fatty acid synthetase were greatest in livers from VMH-lesioned rats. Fasting abolished hyperinsulinemia and most of these observed metabolic alterations. After treatment with anti-insulin serum, the high rate of lipogenesis observed in livers from VMH-lesioned rats was restored toward normal. It is suggested that hyperinsulinemia may be partly responsible for the metabolic disorders observed in livers from nonhyperphagic VMH-lesioned rats.
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PMID:Consequences of ventromedial hypothalamic lesions on metabolism of perfused rat liver. 1 11

The biochemical explanation for lipid accumulation was investigated principally in Candida 107 and, for comparison, in the non-oleaginous yeast Candida utilis. There were no significant differences between these two yeasts in their control of glucose uptake; in both yeasts, the rates of glucose uptake were independent of the growth rate and were higher in carbon-limited chemostat cultures than in nitrogen-limited cultures. There was no lipid turnover in either yeast, as judged from [14C]acetate uptake and subsequent loss of 14C from the lipid of steady-state chemostat cultures. Acetyl-CoA carboxylase from both yeasts was similar in most characteristics except that from Candida 107 was activated by citrate (40% activation at 1 mM). The enzyme from Candida 107 was relatively unstable and, when isolated from nitrogen-limited (lipid-accumulating) cultures, was accompanied by a low molecular weight inhibitor. The reason for lipid accumulation is attributed to the decrease in the intracellular concentration of AMP as cultures become depleted of nitrogen. As the NAD+-dependent isocitrate dehydrogenase of Candida 107, but not C. utilis, requires AMP for activity, the metabolism of citrate through the tricarboxylic acid cycle in the mitochondria becomes arrested. In Candida 107, but not in C. utilis, there is an active ATP:citrate lyase which converts the accumulating citrate, when it passes into the cytosol, into acetyl-CoA and oxaloacetate. The former product is then available for fatty acid biosynthesis which is stimulated by the high ATP concentration within the cells, by the activation of acetyl-CoA carboxylase by citrate and by the provision of NADPH generated as oxaloacetate is converted via malate to pyruvate. Similar characteristics were evident in oleaginous strains of Rhodotorula glutinis and Mucor circinelloides but not in non-oleaginous representatives of these species.
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PMID:A biochemical explanation for lipid accumulation in Candida 107 and other oleaginous micro-organisms. 4 15

Acetyl-CoA carboxylase from liver exhibits a linear inverse relationship between the ratio of enzymic activities at 0 and 2 mM citrate and the extent of phosphorylation by its kinase, and this citrate activity ratio method was used to examine the effect of nutritional conditions on the phosphorylation state of the enzyme. This method showed that the calculated phosphorylation state, being the extent of phosphorylation at sites accessible to carboxylase kinase, was highest in the livers of starved rats, lower in those fed normally, and lower still in starved rats which had been refed for 48 h on a fat-free diet. The actual values were 0.44, 0.26, and 0 mol of P/subunit, respectively, provided that liver samples were frozen rapidly to liquid nitrogen temperatures and extracted with stopping buffers at temperatures well below freezing. Normal homogenization with stopping buffers (containing inhibitors for protein kinases and phosphatases) resulted in much higher calculated phosphorylation states. The effect of nutritional conditions on the phosphorylation state as estimated reported above was confirmed by purifying the carboxylase from livers of rats, measuring the amount of phosphate which could be incorporated by carboxylase kinase, and comparing this with the phosphorylation state calculated from the citrate activity ratio method or the specific activity. Furthermore, treatment with protein phosphatase of carboxylase from starved rats resulted in the largest increase in specific activity, that from the starved/refed rats in the least. Finally, the effects of hyperglycemia on carboxylase and phosphorylase characteristics in the livers of intact rats were ascertained by taking liver samples and preparing crude extracts by the rapid freezing method described above. Hyperglycemia caused a rapid increase in the activity of the carboxylase and a rapid decrease in its putative phosphorylation state as measured by the citrate activity ratio method. Phosphorylase was also dephosphorylated, as indicated by a decrease in phosphorylase a activity. We conclude that the citrate activity ratio method is a valid test for the phosphorylation state of acetyl-CoA carboxylase in crude extracts of tissue.
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PMID:Phosphorylation state of acetyl-coenzyme A carboxylase. II. Variation with nutritional condition. 287 34

Spiramycin biosynthesis in Streptomyces ambofaciens was stimulated in the presence of valine or by sequential addition of some short-chain fatty acids to a culture medium containing an ammonium salt as source of nitrogen. Acetate kinase and acetyl-CoA carboxylase, enzymes that catalysed the formation of precursors of spiramycin biosynthesis (acetyl-CoA and malonyl-CoA), were detected during the active growth and antibiotic production phases. In this latter phase a higher level of acetyl-CoA carboxylase activity was observed with valine (1.02 mumol.min-1.mg protein-1) than with ammonium (0.05 mumol.min-1.mg protein-1) as nitrogen source, while the evolution and the level of acetate kinase activity were the same in both media. Successive addition of acetate and isobutyrate stimulated highly and weakly the acetyl-CoA carboxylase and acetate kinase activity, respectively.
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PMID:Relationship between valine, fatty acids, and spiramycin biosynthesis in Streptomyces ambofaciens. 792 89

Malonyl-CoA is synthesized by acetyl-CoA carboxylase (ACC) and is an inhibitor of fatty acid oxidation. Exercise induces a decline in skeletal muscle malonyl-CoA, which is accompanied by inactivation of ACC and increased activity of AMP-activated protein kinase (AMPK). This study was designed to determine the effect of exercise intensity on the enzyme kinetics of ACC, malonyl-CoA levels, and AMPK activity in skeletal muscle. Male Sprague-Dawley rats were killed (pentobarbital sodium anesthesia) at rest or after 5 min of exercise (10, 20, 30, or 40 m/min at 5% grade). The fast-twitch red and white regions of the quadriceps muscle were excised and frozen in liquid nitrogen. A progressive decrease in red quadriceps ACC maximal velocity (from 28.6 +/- 1.5 to 14.3 +/- 0.7 nmol . g-1 . min-1, P < 0.05), an increase in activation constant for citrate, and a decrease in malonyl-CoA (from 1.9 +/- 0.2 to 0.9 +/- 0.1 nmol/g, P < 0.05) were seen with the increase in exercise intensity from rest to 40 m/min. AMPK activity increased more than twofold. White quadriceps ACC activity decreased only during intense exercise. We conclude that the extent of ACC inactivation during short-term exercise is dependent on exercise intensity.
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PMID:Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase. 933 17

The putative gene encoding acetyl-CoA carboxylase, accA, has been isolated from Aspergillus nidulans. This single-copy gene has an open reading frame (ORF) of 6864 bp and contains two small introns near the 5'-end. A short ORF upstream of the ATG start codon has been identified in this gene by RT-PCR. Based on sequence homology to acetyl-CoA carboxylases from other organisms, putative biotin-, ATP-, HCO3-- and acetyl-CoA- binding sites have been assigned. Northern data and ACC enzyme-activity measurements from A. nidulans suggested that expression of accA was higher in media containing nitrate than ammonia as a sole nitrogen source. Deletion of accA in A. nidulans was unsuccessful. The failure of A. nidulans to grow in the presence of the ACC-specific inhibitor, soraphen A, supplemented with C16-18 fatty acids suggested that ACC is an essential enzyme.
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PMID:Isolation and characterisation of the acetyl-CoA carboxylase gene from Aspergillus nidulans. 987 Nov 20

The hypothesis is advanced that NADP(+)-malic enzyme (ME; EC 1.1.1.40) is an important activity in regulating the extent of lipid accumulation in filamentous fungi. In Mucor circinelloides, a fungus capable of accumulating only 25% (w/w, dry wt) lipid, even under the most propitious conditions, ME disappears 15-20 h after nitrogen exhaustion, coincident with the cessation of lipid accumulation. In contrast, ME in Mortierella alpina, a fungus capable of accumulating 50% (w/w, dry wt) lipid, remains active for over 60 h after N-exhaustion during which time lipid accumulation continues. No other enzyme activity studied, including the lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase, diacyglycerol acyltransferase, ATP: citrate lyase and the NADPH-generating enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP+:isocitrate dehydrogenase, demonstrated any correlation with the accumulation of storage lipid in either fungus. Full activity of ME is restored in Mr. circinelloides within 4 h by adding NH4+ to the cultures, but this is prevented by adding cycloheximide as an inhibitor of protein synthesis. This suggests that the decrease in ME activity occurs due to down-regulation of the ME gene.
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PMID:The role of malic enzyme in the regulation of lipid accumulation in filamentous fungi. 1046 57

Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, an essential substrate for fatty acid biosynthesis and a potent inhibitor of fatty acid oxidation. Here, we provide evidence that glutamate may be a physiologically relevant activator of ACC. Glutamate induced the activation of both major isoforms of ACC, prepared from rat liver, heart, or white adipose tissue. In agreement with previous studies, a type 2A protein phosphatase contributed to the effects of glutamate on ACC. However, the protein phosphatase inhibitor microcystin LR did not abolish the effects of glutamate on ACC activity. Moreover, glutamate directly activated purified preparations of ACC when protein phosphatase activity was excluded. Phosphatase-independent ACC activation by glutamate was also reflected by polymerization of the enzyme as judged by size-exclusion chromatography. The sensitivity of ACC to direct activation by glutamate was diminished by treatment in vitro with AMP-activated protein kinase or cAMP-dependent protein kinase or by beta-adrenergic stimulation of intact adipose tissue. We conclude that glutamate, an abundant intracellular amino acid, induces ACC activation through complementary actions as a phosphatase activator and as a direct allosteric ligand for dephosphorylated ACC. This study supports the general hypothesis that amino acids fulfill important roles as signal molecules as well as intermediates in carbon and nitrogen metabolism.
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PMID:Bimodal activation of acetyl-CoA carboxylase by glutamate. 1075 75

Acetyl-CoA carboxylase catalyzes the first committed step in the synthesis of long chain fatty acids. In this study, we observed that treatment of 3T3-L1 cells with biotin chloroacetylated at the 1' nitrogen reduced the enzymatic activity of cytosolic acetyl-CoA carboxylase and concomitantly inhibited the differentiation of 3T3-L1 cells in a dose-dependent manner. Treatment with chloroacetylated biotin blocked the induction of PPARgamma, STAT1, and STAT5A expression that normally occurs with adipogenesis. Moreover, addition of chloroacetylated biotin inhibited lipid accumulation, as judged by Oil Red O staining. Our results support recent studies that indicate that acetyl-CoA carboxylase may be a suitable target for an anti-obesity therapeutic.
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PMID:A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. 1190 24

Twenty-six multiparous Holstein cows were used to examine the effects of prepartum energy and protein intake on periparturient metabolism and lactation performance. Two levels of energy, 1.65 Mcal/kg of net energy for lactation (NEL) and 1.30 Mcal/kg of NEL, and two levels of protein, 17.0% CP and 12.5% CP, were tested according to a factorial arrangement in a randomized block design. Dietary treatments were fed ad libitum from 21 d before expected calving date to the day of calving. After calving, all cows were fed the same diet. Increased nutrient density did not affect prepartum feed intake, but postpartum intake was higher for cows fed the high-energy diets. Treatment had no effect on cow body weight and body condition score, however, cows fed the high-energy diets were in greater energy balance throughout the study. Milk and milk component yields were unaffected by treatment. Cows fed the high-energy diets had lower plasma nonesterified fatty acid concentrations than cows fed the low energy diets (354.3 vs. 439.9 mumol/L). Hepatic triglyceride concentrations were lower for cows on the high-energy diets than for those on the low-energy diets. Liver glycogen was unaffected by treatment. Acetyl-CoA carboxylase and fatty acid synthase abundance was significantly lower at calving than pretreatment, and higher for cows on the high-energy diets relative to those on the low-energy diets. The activity of acetyl-CoA carboxylase and lipoprotein lipase was greatly decreased with the onset of lactation. Increased protein intake prepartum resulted in elevated plasma beta-hydroxybutyrate concentrations postpartum. Prepartum plasma urea nitrogen was increased and 3-methylhistidine decreased by the high protein treatments. Overall, increased energy density of prepartum diets had beneficial effects on feed intake and lipid metabolism but did not improve lactation performance. Increasing the protein content of the prepartum diet did not appear to confer any advantages to cow productivity.
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PMID:Peripartum performance and metabolism of dairy cows in response to prepartum energy and protein intake. 1236 65


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