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)

Glucagon and N,(6)O(2)-dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (Bt(2)cAMP) inhibit fatty acid synthesis from acetate by more than 90% and prevent citrate formation in chick hepatocytes metabolizing glucose. With substrates that enter glycolysis at or below triose-phosphates, e.g., fructose, lactate, or pyruvate, Bt(2)cAMP has no effect on the citrate level and its inhibitory effect on fatty acid synthesis is substantially reversed. Because acetyl-CoA carboxylase requires a tricarboxylic acid activator for activity, it is proposed that regulation of fatty acid synthesis by Bt(2)cAMP is due, in part, to changes in the citrate level. Reduced citrate formation appears to result from a cAMP-induced inhibition of glycolysis. Bt(2)cAMP inhibits (14)CO(2) production from [1-(14)C]-, [6-(14)C]-, and [U-(14)C]glucose and has little effect on (14)CO(2) formation from [1-(14)C]- or [2-(14)C]pyruvate or from [1-(14)C]fructose. [(14)C]Lactate formation from glucose is depressed 50% by Bt(2)cAMP. In the presence of an inhibitor of mitochondrial pyruvate transport lactate accumulation is enhanced, but continues to be lowered 50% by Bt(2)cAMP. The activity of phosphofructokinase is greatly decreased in Bt(2)cAMP-treated cells while the activities of pyruvate kinase and acetyl-CoA carboxylase are unaffected. It appears that decreased glycolytic flux and decreased citrate formation result from depressed phosphofructokinase activity. Fatty acid synthesis from [(14)C]acetate is partially inhibited by Bt(2)cAMP in the presence of fructose, lactate, and pyruvate despite a high citrate level. Incorporation of [(14)C]fructose, [(14)C]pyruvate, or [(14)C]lactate into fatty acids is similarly depressed by Bt(2)cAMP. Synthesis of cholesterol from [(14)C]acetate or [2-(14)C]pyruvate is unaffected by Bt(2)cAMP. These results implicate a second site of inhibition of fatty acid synthesis by Bt(2)cAMP that involves the utilization, but not the production, of cytoplasmic acetyl-CoA.-Clarke, S. D., P. A. Watkins, and M. D. Lane. Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation.
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PMID:Acute control of fatty acid synthesis by cyclic AMP in the chick liver cell: possible site of inhibition of citrate formation. 23 Feb 68

Several important metabolic functions of the mammalian liver have been shown to be located in zones with respect to the complex microcirculation of the organ. The zonal distribution of the cytosolic component of the acetyl-CoA synthetase activity has been investigated using the dual-digitonin-pulse-perfusion technique, which allows highly zone-selective sampling of cytosol from the periportal and perivenous zone of rat liver. Approximately 80% of the cytosolic enzymes are eluted from the hepatocytes in the periportal and perivenous sub-zones affected by digitonin, while less than 1% of the glutamate dehydrogenase activity (a marker enzyme of the mitochondrial compartment) is eluted. A twofold higher activity of the cytosolic form of acetyl-CoA synthetase is found in the periportal zone compared to the perivenous zone in fed male rats. Following a fasting/refeeding transition, this activity gradient is abolished in a manner similar to that observed for the enzyme acetyl-CoA carboxylase. Since the latter enzyme is utilizing the product of acetyl-CoA synthetase, acetyl-CoA, the similarity in the observed regulation suggests a functional coupling between cytosolic acetate activation and fatty-acid synthesis.
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PMID:Periportal zonation of the cytosolic acetyl-CoA synthetase of male rat liver. 134 65

1. Isolated hepatocytes from chicks were used to study the effects of pantethine supplementation to incubation medium on in vitro lipogenesis, CO2 production and beta-oxidation of fatty acid. 2. In vitro lipogenesis, determined by the incorporation of 1-[14C]acetate into total lipid and various lipid fractions, as depressed in concordance with the increase of pantethine concentration in the medium. 3. Incubation of isolated hepatocytes with pantethine resulted in a significant decrease (P < 0.01) in the activities of acetyl-CoA carboxylase and fatty acid synthetase. 4. The results suggest that in vitro fatty acid synthesis from 1-[14C]acetate was depressed and CO2 production was elevated in hepatocytes of chicks through pantethine addition to the medium at a low level.
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PMID:Effects of pantethine on lipogenesis and CO2 production in the isolated hepatocytes of the chick (Gallus domesticus). 135 45

(1) The rate of palmitate oxidation in the 7800 C1 Morris hepatoma cells was about 60% of the activity observed in hepatocytes. The stimulatory effect of glucagon in hepatocytes was not observed in the hepatoma cells. The rate of fatty acid synthesis from [2-14C]acetate in the hepatoma cells was 1/20 of the activity in hepatocytes. The conversion of [2-14C]acetate to cholesterol was not different in the two kinds of cell. (2) Acetyl-CoA carboxylase and fatty acid synthetase were significantly decreased in the hepatoma cells. The hepatoma cells had, however, raised activities of malate dehydrogenase (decarboxylating), and glucose-6-phosphate and 6-phosphogluconate dehydrogenases. (3) The activities of the enzymes were not affected by different concentrations of glucose or palmitate in the culture medium. Insulin, dexamethasone, triiothyronine and glucagon had no effect on the enzyme activities. This is in contrast to the adaptation of the peroxisomal beta-oxidation system, which is induced by fatty acids and modified by hormones.
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PMID:Activities of enzymes of lipid metabolism in Morris hepatoma 7800 C1 cells. 256 35

Acetyl-CoA carboxylase activity was measured in digitonin-permeabilized rat hepatocytes by coupling the carboxylase reaction to the fatty acid synthase reaction. Using this assay the activity of acetyl-CoA carboxylase was covariant with the rate of fatty acid synthesis. Insulin and the tumor promotor phorbol myristate acetate were found to stimulate, and glucagon and noradrenaline to inhibit both cellular parameters. The stimulation of acetyl-CoA carboxylase by insulin developed slowly (15 to 30 min) whereas the phorbol myristate acetate effect developed faster (within 15 min). The inhibition of the enzyme caused by glucagon was already apparent within 1 min after hormone addition. Inhibition by noradrenaline, in the presence of propranolol, was also quite rapid and occurred within 2 min after addition of the agonist.
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PMID:Time course of hormonal effects on acetyl-CoA carboxylase as measured in digitonin-permeabilized rat hepatocytes. 257 37

Fatty acid metabolism was studied in periportal and perivenous hepatocytes isolated by the method of Chen & Katz [Biochem. J. (1988) 255, 99-104]. The rate of fatty acid synthesis and the activity of acetyl-CoA carboxylase were markedly enhanced in perivenous hepatocytes as compared with periportal cells. However, the response of these two parameters to short-term modulation by cellular effectors such as the hormones insulin and glucagon, the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate and the xenobiotics ethanol and acetaldehyde was similar in the two zones of the liver. In addition, perivenous hepatocytes showed a higher capacity of esterification of exogenous fatty acids into both cellular and very-low-density-lipoprotein lipids. Nevertheless, no difference between the two cell sub-populations seemed to exist in relation to the secretion of very-low-density lipoproteins. On the other hand, the rate of fatty acid oxidation was increased in periportal cells. This could be accounted for by a higher activity of carnitine palmitoyltransferase I and a lower sensitivity of this enzyme to inhibition by malonyl-CoA in the periportal zone. No differences were observed between periportal and perivenous hepatocytes in relation to the short-term response of fatty acid oxidation and carnitine palmitoyltransferase I activity to the cellular modulators mentioned above. In conclusion, our results show that: (i) lipogenesis is achieved at higher rates in the perivenous zone of the liver, whereas the fatty-acid-oxidative process occurs with a certain preference in the periportal area of this organ; (ii) the short-term response of the different fatty-acid-metabolizing pathways to cellular effectors is quantitatively similar in the two zones of the liver.
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PMID:Zonation of fatty acid metabolism in rat liver. 257 74

Lipogenic and lipolytic capacities were examined in fasted and nonfasted 28-day-old chicks from high-weight (HW) and low-weight (LW) selected lines. Lipogenesis was assessed in liver and bone (sternum) tissues through the activities of malic enzyme (EC 1.1.1.40), citrate cleavage enzyme (EC 4.1.3.8), and acetyl coenzyme A carboxylase (EC 6.4.1.2), as well as through the in vitro incorporation of acetate-1-14C into liver and bone lipid fractions. Lipolysis was estimated through the in vitro release of free fatty acids (FFA) from abdominal adipose tissue and through plasma FFA. Fasting depressed lipogenesis and increased lipolysis. Regardless of the feeding state, LW chicks exhibited higher lipogenic and lipolytic capacities than their HW counterparts, suggesting that lipid degradation may be relatively more important than synthesis in determining net fat deposition. In addition, the incorporation of radioactive acetate into bone lipid was associated with detectable activity of lipogenic enzymes, providing further evidence that the skeleton is an important site of lipogenesis in the chicken.
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PMID:Lipogenesis and lipolysis in fed and fasted chicks from high and low body weight lines. 286 Jun 43

Data are summarized from several papers on the effects of biotin deficiency on lipid metabolism, especially fatty acid synthesis, in chicks. Biotin deficiency inhibits in vivo lipogenesis and hepatic acetyl-CoA carboxylase (ACC) activity. Although acetate incorporation into fatty acids is inhibited in biotin-deficient chicks, malonate incorporation is not inhibited. In fact, dietary malonic acid stimulates lipogenesis during biotin deficiency as measured by total carcass fatty acid content. Biotin-deficient chicks exhibit altered hepatic and whole body fatty acid composition in comparison with control chicks. The deficiency results in an increased proportion of the 16-carbon to 18-carbon fatty acids, and the most striking increase is for palmitoleic (16:1) acid. Biotin deficiency increases the relative incorporation of palmitate and stearate into phospholipids and decreases the relative incorporation of these fatty acids into triglycerides. Finally, mercury stimulates lipogenesis in biotin-deficient, but not in control, chicks by an unknown mechanism.
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PMID:Biotin effects on fatty acid synthesis in chicks. 286 76

With hepatocytes in suspension, freshly isolated from meal-fed rats, no significant effect of ionomycin on the rate of de novo fatty acid synthesis was observed, whereas phorbol myristate acetate (PMA) was strongly stimulatory. The combination of ionomycin and PMA produced the same stimulation as was seen with PMA alone. Stimulation of fatty acid synthesis by vasopressin was comparable and not additive to that observed with PMA, indicating that activation of protein kinase C is solely responsible for this metabolic effect of vasopressin. Both vasopressin and PMA increased acetyl-CoA carboxylase activity in isolated rat hepatocytes.
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PMID:No synergism between ionomycin and phorbol ester in fatty acid synthesis by isolated rat hepatocytes. 287 2

Acetyl-CoA carboxylase (EC 6.4.1.2) in hepatocytes from meal-fed rats was activated by phorbol myristate acetate (PMA) in a time- and concentration-dependent fashion. This activation can account for the PMA-induced stimulation of de novo fatty acid synthesis. Purified rat-liver acetyl-CoA carboxylase was found to be phosphorylated and activated by protein kinase C, thus providing a possible mechanism for the metabolic action of PMA in intact hepatocytes.
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PMID:Stimulation by a tumor-promoting phorbol ester of acetyl-CoA carboxylase activity in isolated rat hepatocytes. 288 May 84


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