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)

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

2-Methylcitrate was tested in vitro on enzymes which interact with citrate and isocitrate. It was found to inhibit citrate synthase, aconitase, the NAD+- and NADP+-linked isocitrate dehydrogenase. This inhibition was competitive in nature except in the case of aconitase, and the Ki for all the enzymes was in the range of 1.5-7.6 mM. Phosphofructokinase was also inhibited by 2-methylcitrate with 50% inhibition achieved at 1 mM. ATP-citrate lyase and acetyl-CoA carboxylase were not inhibited by this compound. 2-Methylcitrate was not a substrate for ATP-citrate lyase. Acetyl-CoA carboxylase was activated by 2-methylcitrate with a Ka of 2.8 mM. The apparent Km (3.3 mM) for 2-methylcitrate for the mitochondrial citrate transporter was about 10-fold higher than the apparent Km (0.26 mM) for citrate. The tricarboxylase carrier can also be inhibited by low concentrations (0.2 mM) of 2-methylcitrate when the concentration of citrate is close to the apparent Km. Accumulation of 2-methylcitrate inside the mitochondrion, therefore, might lead to inhibition of enzymes in the citric acid cycle and thereby contribute to the ketogenesis and hypoglycemia seen under these conditions.
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PMID:Effect of 2-methylcitrate on citrate metabolism: implications for the management of patients with propionic acidemia and methylmalonic aciduria. 12 73

1. The metabolic response of livers to perfusion with ethanol with and without avenaciolide, has been followed by measuring the perfusate levels of glucose, lactate, pyruvate, beta-hydroxybutyrate, ethanol, amino acids, urea and lipid. 2. Analysis of the perfused livers showed changes in the activities of some of the key enzymes of glycolysis, gluconeogenesis and lipogenesis. Ethanol perfusion decreased the levels of phosphofructokinase, glucokinase and cytosolic isocitrate dehydrogenase, while avenaciolide lowered pyruvate carboxylase and phosphoenolpyruvate carboxykinase as well as glucokinase. Isocitrate dehydrogenase and phosphofructokinase were unchanged, but the ionophore increased the level of fructose-1,6-diphosphatase. Ethanol plus avenaciolide showed the same pattern as ethanol alone, together with the decrease in phosphoenolpyruvate carboxykinase found with avenaciolide. 3. Neither ethanol nor avenaciolide had any effect on kexokinase, pyruvate kinase or acetyl-CoA carboxylase. There were small changes in glucose-6-phosphatase and malic enzyme, and a tendency for citrate lyase levels to decline in avenaciolide perfusions.
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PMID:The actions of avenaciolide and ethanol on glucose metabolism and on related enzyme activities in the isolated perfused rat liver. 94 10

Addition of triiodothyronine (T3) to chick-embryo hepatocytes in culture causes increased accumulations of malic enzyme, fatty acid synthase, acetyl-CoA carboxylase and their mRNAs. H-8 and other protein kinase inhibitors inhibited the T3-induced accumulations of these lipogenic enzymes and their mRNAs but had no effect on the activities of 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase, enzymes not induced by T3 in chick-embryo hepatocytes. H-8 also had no effect on the activities of malic enzyme, fatty acid synthase, and acetyl-CoA carboxylase in hepatocytes not treated with T3. Synthesis of soluble protein, levels of mRNAs for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, and induction of metallothionein mRNA by Zn2+ were unaffected by H-8 at concentrations that inhibited the T3-induced accumulation of lipogenic enzymes and their mRNAs. H-8 inhibited T3-induced transcription of the genes for both malic enzyme and fatty acid synthase but had little effect on transcription of the beta-actin or glyceraldehyde-3-phosphate dehydrogenase genes or on total RNA synthesis in isolated nuclei. H-8 also had no effect on binding of T3 to its nuclear receptor. In isolated nuclei, H-8 inhibited phosphorylation of total protein by 15-20%. Phosphorylation of only one major protein was consistently and substantially inhibited, indicating that the effect of H-8 was selective. These results suggest that on-going protein phosphorylation is required specifically for stimulation of transcription of the lipogenic genes by T3.
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PMID:Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl-coenzyme A carboxylase, and their mRNAs are blocked by protein kinase inhibitors. Transcription is the affected step. 168 Jan 29

1. Mammary tissue was obtained from rabbits at various stages of pregnancy and lactation and used for tissue-slice incubations (to measure the rate of fatty acid synthesis and CO(2) production) and to determine relevant enzymic activities. A biphasic adaptation in fatty acid synthetic capacity during lactogenesis was noted. 2. The first lactogenic response occurred between day 15 and 24 of pregnancy. Over this period fatty acid synthesis (from acetate) increased 14-fold and the proportions of fatty acids synthesized changed to those characteristic of milk fat (77-86% as C(8:0)+C(10:0) acids). 3. The second lactogenic response occurred post partum as indicated by increased rates of fatty acid synthesis and CO(2) production (from acetate and glucose) and increased enzymic activities. 4. Major increases in enzymic activities between mid-pregnancy and lactation were noted for ATP citrate lyase (EC 4.1.3.8), acetyl-CoA synthetase (EC 6.2.1.1), acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthetase, glucose 6-phosphate dehydrogenase (EC 1.1.1.49), and 6-phosphogluconate dehydrogenase (EC 1.1.1.44). Smaller increases in activity occurred with glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) and NADP(+)-isocitrate dehydrogenase (EC 1.1.1.42) and the activity of NADP(+)-malate dehydrogenase (EC 1.1.1.40) was negligible at all periods tested. 5. During pregnancy and lactation there was a close temporal relationship between fatty acid synthetic capacity and the activities of ATP citrate lyase (r=0.94) and acetyl-CoA carboxylase (r=0.90).
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PMID:Metabolic adaptations during lactogenesis. Fatty acid synthesis in rabbit mammary tissue during pregnancy and lactation. 415 42

1. Changes in the activities of acetyl-CoA carboxylase (EC 6.4.1.2), phosphofructokinase (EC 2.7.1.11), aldolase (EC 4.1.2.13), extramitochondrial aconitate hydratase (EC 4.2.1.3) and NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42) have been measured in the livers of developing rats from late foetal life to maturity. 2. The effect of altering the weaning time on some enzymes associated with lipogenesis has been studied. Weaning rats at 15 days of age instead of 21 days results in an immediate increase in the activity of ;malic' enzyme (EC 1.1.1.40) whereas the activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and ATP citrate lyase (EC 4.1.3.8) did not increase until 4-5 days and acetyl-CoA carboxylase 2-3 days after early weaning. Weaning rats on to an artificial-milk diet led to complete repression of the rise in activity of hepatic enzymes associated with lipogenesis normally found on weaning, except for ;malic' enzyme, which increased in activity after 20 days of age. 3. The effect of intraperitoneal injections of glucagon, cortisol, growth hormone and thyroxine on the same hepatic enzymes has been investigated. Only thyroxine had any effect on enzyme activities and caused a 20-fold increase in ;malic' enzyme activity and a twofold increase in ATP citrate lyase activity. 4. The activities of hepatic glucose 6-phosphate dehydrogenase and ;malic' enzyme are higher in adult female than in adult male rats and it has been shown that this sex difference in enzyme activities is due to both male and female sex hormones. 5. Hepatic malate, citrate, pyruvate, glucose 6-phosphate and phosphoenolpyruvate concentrations have been measured throughout development. 6. The results are discussed in relation to the dietary and hormonal control of hepatic enzyme activities during development.
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PMID:Factors involved in changes in hepatic lipogenesis during development of the rat. 424 18

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.
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PMID:The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions. 424 59

Crossbred steers (seven to nine per treatment) fed a pelleted alfalfa hay diet were biopsied (preinfusion) to obtain subcutaneous adipose tissue (SAT). Five days later a continuous intravenous infusion was begun of either 0.9% NaCl, glucose (2.75 moles/day), DL-lactate (5.5 moles/day of L-lactate), propionate (5.5 moles/day) or acetate (8.25 moles/day); after infusion for 14 days, a second biopsy sample of SAT was obtained. Glucose and DL-lactate infusion increased acetyl-CoA carboxylase activity about 12-fold compared to preinfusion activity of 5.3 +/- 4.2 nmoles/minute/g of wet weight. Glucose infusion induced activities of fatty acid synthetase (2.6 fold) and NADP+-malate dehydrogenase (7-fold) relative to preinfusion activities of 26.8 +/- 5.2 and 30.3 +/- 15.5 nmoles/minute/g of wet weight, respectively. Glucose, DL-lactate and propionate infusion increased NADP-isocitrate dehydrogenase activity 20-30% compared to preinfusion activity. Activity of NAD-malate dehydrogenase was not altered by any infusion treatment (P > 0.05). Activity of ATP-citrate lyase was decreased 48% by lactate infusion. Glucose, lactate and propionate infusion increased the rates of lactate and glucose incorporation into fatty acids in SAT incubated in vitro three to fourfold over preinfusion incorporation rates. Increased availability of glucose or gluconeogenic precursors may be responsible for induction of lipogenesis in steers fed high concentrate diets.
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PMID:Effects of intravenous infusions of glucose, lactate, propionate or acetate on the induction of lipogenesis in bovine adipose tissue. 742 Feb 5

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

Various inorganic and organic nitrogen sources were used to compare their effects on the lipogenesis and the activities of lipogenic enzymes (providing acetyl-CoA and donating NADPH) in gamma-linolenic acid-producing fungus Cunninghamella echinulata. Lipid accumulation was enhanced by organic nitrogen, among them the presence of corn-steep led to almost 40% oil in the biomass. While organic nitrogen increased activities of acetyl-CoA carboxylase (ACC) and malic enzyme (ME), ATP:citrate lyase (ACL) was rapidly enhanced by ammonium ion. The use of NaNO(3) resulted in high activities of glucose 6-phosphate dehydrogenase (GPD) and 6-phosphogluconate dehydrogenase (PGD). NADP-isocitrate dehydrogenase (NADP-ICD) was more active when the fungus utilized all inorganic N-compounds. The rise of nitrogen concentration in medium was accompanied with reduced lipid accumulation and a fall of ACL, ACC, and ME. In contrast, N-sufficient conditions favored biomass growth and elevated activities of GPD and PGD. Kinetic experiments also suggest that a significant portion of the required acetyl-CoA was being provided via ACL and ACC, and ME (probably coupled with GPD) channeled the NADPH into the fatty acid biosynthesis. The contribution of the lipogenic enzymes to metabolic pathways other than lipogenesis is also discussed.
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PMID:Effect of nitrogen sources on the activities of lipogenic enzymes in oleaginous fungus Cunninghamella echinulata. 1250 58


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