Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of nutritional status on fatty acid synthesis in brown adipose tissue was compared with the effect of cold-exposure. Fatty acid synthesis was measured in vivo by 3H2O incorporation into tissue lipids. The activities of acetyl-CoA carboxylase and fatty acid synthetase and the tissue concentrations of malonyl-CoA and citrate were assayed. 2. In brown adipose tissue of control mice, the tissue content of malonyl-CoA was 13 nmol/g wet wt., higher than values reported in other tissues. From the total tissue water content, the minimum possible concentration was estimated to be 30 microM 3. There were parallel changes in fatty acid synthesis, malonyl-CoA content and acetyl-CoA carboxylase activity in response to starvation and re-feeding. 4. There was no correlation between measured rates of fatty acid synthesis and malonyl-CoA content and acetyl-CoA carboxylase activity in acute cold-exposure. The results suggest there is simultaneous fatty acid synthesis and oxidation in brown adipose tissue of cold-exposed mice. This is probably effected not by decreases in the malonyl-CoA content, but by increases in the concentration of free long-chain fatty acyl-CoA or enhanced peroxisomal oxidation, allowing shorter-chain fatty acids to enter the mitochondria independent of carnitine acyltransferase (overt form) activity.
 ...
PMID:Regulation of fatty acid synthesis and malonyl-CoA content in mouse brown adipose tissue in response to cold-exposure, starvation or re-feeding. 288 57

A soluble protein that binds malonyl-CoA without requiring cofactors has been purified from rat liver. Until saturated, it competes with fatty acid synthetase for free malonyl-CoA, temporarily reducing the rate of fatty acid synthesis at low levels of malonyl-CoA, as in fatty acid synthetase--coupled assays for acetyl-CoA carboxylase. These assays yield low estimates for carboxylase activity with crude and partially purified homogenates containing the malonyl-CoA-binding protein. The protein does not inhibit assays for carboxylase activity that measure nonvolatile radioactivity incorporated from bicarbonate or NADH oxidation coupled to ADP formation. It has an Mr of 180,000 and a subunit of 90,000. It has a lower affinity for ATP, ADP, and acetyl-CoA and none for CO2 or fatty acid synthetase. No enzymatic function has been identified. The protein may regulate malonyl-CoA-binding enzymes.
 ...
PMID:A malonyl-CoA-binding protein from liver. 288 60

Incorporation of [14C]acetate or [14C]pyruvate into fatty acids in isolated corn seedling chloroplasts was inhibited 90% or greater by 10 microM sethoxydim or 1 microM haloxyfop. At these concentrations, neither sethoxydim nor haloxyfop inhibited [14C]acetate incorporation into fatty acids in isolated pea chloroplasts. Sethoxydim (10 microM) and haloxyfop (1 microM) did not inhibit incorporation of [14C]malonyl-CoA into fatty acids in cell free extracts from corn tissue cultures. Acetyl coenzyme A carboxylase (EC 6.4.1.2) from corn seedling chloroplasts was inhibited by both sethoxydim and haloxyfop, with I50 values of 2.9 and 0.5 microM, respectively. This enzyme in pea was not inhibited by 10 microM sethoxydim or 1 microM haloxyfop.
 ...
PMID:Inhibition of plant acetyl-coenzyme A carboxylase by the herbicides sethoxydim and haloxyfop. 289 54

In rats weaned on a high-carbohydrate diet, hepatic fatty acid oxidation capacity is decreased when compared to suckling rats. Previous studies (Benito et al., 1979) suggested that a malonyl-CoA-dependent mechanism could be at the origin of this decrease. Studies on isolated hepatocytes show that despite, respectively, a low and a high lipogenic rate in suckling and weaned rats, malonyl-CoA concentrations are similar in the two groups. This might be due to the lower ratio fatty acid synthetase/acetyl-CoA carboxylase (EC 6.4.1.2) activities during suckling than after weaning. Different rates of hepatic fatty acid oxidation despite similar malonyl-CoA concentrations can be explained by the 2.5-fold higher carnitine palmitoyltransferase I (EC 2.3.1.21) activity in suckling rats together with a 7-fold higher Ki for malonyl-CoA. This precludes a tight control of fatty acid oxidation by [malonyl-CoA] in suckling rats. Weaning on a high-fat carbohydrate-free diet abolishes the changes previously described for the kinetic characteristics of carnitine palmitoyltransferase I suggesting that nutritional modifications rather than a developmental stage are involved. Thus, during the suckling-weaning transition, a variation of [malonyl-CoA] is not responsible for the decrease in hepatic fatty acid oxidation. It involves, in addition, a decrease in carnitine palmitoyltransferase I activity and an increase of the sensitivity of this enzyme to malonyl-CoA.
 ...
PMID:Decreased hepatic fatty acid oxidation at weaning in the rat is not linked to a variation of malonyl-CoA concentration. 289 1

The carnitine system functions in the transport of activated acyl groups over the mitochondrial inner membrane, and is needed for oxidation of long-chain fatty acids by all mitochondria. The rate of cardiac fatty acid oxidation is determined by availability of fatty acids, oxygen and the activity of carnitine palmitoyltransferase I, which is regulated by a variety of factors. It is inhibited by malonyl-CoA, which in rat heart was found to be synthesized by acetyl-CoA carboxylase. It is also inhibited by long-chain acylcarnitine. Linoleoylcarnitine was found to be a better inhibitor than palmitoylcarnitine. The concentration of carnitine in human heart, muscle and other tissues is much higher than is needed for the optimal beta-oxidation rate. In contrast to controls, we found in several myopathic patients that extra carnitine (from 1/2 to 5 mM) caused a considerable increase in beta-oxidation rate of isolated muscle mitochondria. In some of these patients we detected medium-chain acyl-CoA dehydrogenase deficiency. Patients with primary carnitine deficiency caused by a renal carnitine leak often show cardiomyopathy, which completely disappears under carnitine therapy. Cardiomyopathy may also be the cause of secondary carnitine deficiency resulting from a mitochondrial defect in acyl-CoA metabolism, or by the mitochondrial defect itself, which may be induced by drugs or viral attack, or be the result of a genetic error. In cardiomyopathic patients with a (subclinical) myopathy, study of isolated mitochondria and homogenate from skeletal muscle may reveal a mitochondrial dysfunction, which, in some patients, is treatable by dietary measures and supplementation with vitamins, CoQ and/or carnitine. When the cause of cardiomyopathy is not known, determination of plasma carnitine and carnitine supplementation of hypocarnitinemic patients is of great therapeutic value.
 ...
PMID:The role of the carnitine system in myocardial fatty acid oxidation: carnitine deficiency, failing mitochondria and cardiomyopathy. 331 Oct 10

Fatty acid-biosynthetic activity in rat liver cytosol fractions is much greater when the bivalent cation in the assay system is Mn(2+) than when it is Mg(2+). This difference between bivalent cations can be abolished if the cytosol fractions are preincubated with isocitrate and the bivalent cation for 30min before assay of fatty acid-biosynthetic activity. In a search for the biochemical basis of this phenomenon, the following differences between Mg(2+) and Mn(2+) were established: (1) Mn(2+) promotes acetyl-CoA carboxylase activity of the protomeric form of the enzyme under conditions in which Mg(2+) does not; (2) Mn(2+)+ATP have little inhibitory effect on the polymerization of acetyl-CoA carboxylase whereas Mg(2+)+ATP are markedly inhibitory; (3) under conditions in which utilization of malonyl-CoA in condensation reactions is prevented, the steady-state concentration of malonyl-CoA formed by a cytosol fraction is much greater with Mn(2+) than with Mg(2+). The role that each of these specific differences between Mn(2+) and Mg(2+) might play in causing liver cytosol preparations to have greater fatty acid-biosynthetic activity in the presence of Mn(2+) is discussed.
 ...
PMID:Differences between manganese and magnesium ions with regard to fatty acid biosynthesis, acetyl-coenzyme A carboxylase activity and malonyl-coenzyme A decarboxylation. 547 65

Extracts from human platelets contain the enzymes of de novo fatty acid biosynthesis. The pattern of incorporation of acetate-1-(14)C into fatty acids by intact platelets indicates that these enzymes function in platelets. The level of acetyl-coenzyme A (CoA) carboxylase activity in extracts of platelets from normal subjects is 0.036 +/-0.01 mmumole of malonyl-CoA formed per min per mg of protein and that of fatty acid synthetase is 0.075 +/-0.016 mmumole of malonyl-CoA utilized per min per mg of protein. Thus, platelets are the only formed elements of the blood capable of de novo fatty acid synthesis. The capacity of platelets to synthesize fatty acids is similar to human liver based on enzyme activity per milligram of soluble protein.Acetyl-CoA carboxylase was purified 16-fold from platelet extracts, and this partially purified enzyme was compared to enzyme from rat liver. The two enzymes were similar with respect to requirements, substrate affinities, pH profile of activity, inhibition by malonyl-CoA, and aggregation in the presence of citrate. Thus, while fatty acid synthesis may serve a different function in platelets than in liver, the properties of acetyl-CoA carboxylase from these tissues are alike. The levels of the enzymes of fatty acid synthesis were significantly higher in platelets from splenectomized subjects than in controls. Acetyl-CoA carboxylase levels were 0.086 +/-0.027 mmumole of malonyl-CoA formed per min per mg of protein, and fatty acid synthetase levels were 0.151 +/-0.039 mmumole of malonyl-CoA utilized per min per mg of protein. These changes in the enzymes of fatty acid synthesis occurred promptly after splenectomy with peak values being reached within 7-10 days.
 ...
PMID:Lipid metabolism in human platelets. I. Evidence for a complete fatty acid synthesizing system. 576 18

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.
 ...
PMID:Acute effects of insulin on fatty acid metabolism in isolated rat hepatocytes. 610 68

Polyunsaturated fats (PUFA) suppressed hepatic fatty acid synthesis and the activities of lipogenic enzymes more effectively than did saturated fats. The activity of glycolytic enzymes--glucokinase, phosphofructokinase and pyruvate kinase--were not affected by PUFA. The absolute rate of liver fatty acid synthesis after meal ingestion was very similar to the maximal activities of acetyl-CoA carboxylase and fatty acid synthetase. When PUFA was supplemented to a fat-free diet, the activities of carboxylase and synthetase decreased similarly over 3 days. During the 3 days, the concentration of liver malonyl-CoA (after meal ingestion) did not significantly differ between the fat-free and PUFA dietary treatments. Apparently PUFA feeding caused a coordinate decrease in the utilization and production of malonyl-CoA which resulted in no net change in malonyl-CoA pool size. Thus the mechanism by which PUFA suppresses fatty acid synthesis appears to be by coordinately and specifically reducing the amount of carboxylase and fatty acid synthetase.
 ...
PMID:Coordinate suppression of liver acetyl-CoA carboxylase and fatty acid synthetase by polyunsaturated fat. 610 7

The activity of 3-hydrosy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and the rate of mevalonic acid (MVA) synthesis from [I-14C]acetyl-CoA and [2-14C]malonyl-CoA in the soluble (X140000 g) and microsomal fractions of rat liver and in a reconstituted system containing the soluble and microsomal fractions were studied. The changes in the activity of HMG-CoA reductase and the rate of MVA biosynthesis in the fractions at different times of the day were analyzed. The daily rhythms of the rate of acetyl-CoA and malonyl-CoA incorporation into squalene, sterols and fatty acids in the postmitochondrial fraction and the daily changes in the acetyl-CoA carboxylase activity of the soluble fraction of rat liver were compared. The incorporation of labelled acetyl-CoA and malonyl-CoA into MVA showed that the latter can be synthesized from these two substrates both in the soluble and microsomal fractions. Malonyl-CoA is a preferable substrate for MVA synthesis in the soluble fraction. MVA synthesis from acetyl-CoA proceeds fastr in the intact and solubilized microsomes than in the soluble fraction. The activity of HMG-CoA reductase was found in the soluble and microsomal fractions in practically equal amounts. The enzyme activity was increased in the microsomal fraction after its solubilization. The rate of MVA biosynthesis from acetyl-CoA and the activity of HMG-CoA reductase in the soluble fraction are practically unaffected by day-to-night changes. The activity of HMG-CoA reductase and MVA biosynthesis from acetyl-CoA in the intact and solubilized microsomal fractions reached their maximal values in the middle of the dark period. The rate of MVA biosynthesis from malonyl-CoA was decreased in the middle of the dark period in all fractions studied and reached its maximum in the middle of the light period. The daily rhythms of the acetyl-CoA carboxylase activity in the soluble fraction and the rate of MVA biosynthesis from malonyl-CoA in all fractions show a coincidence. a comparison of incorporation by the postmitochondrial fractions of acetyl-CoA and malonyl-CoA into the total non-saponified lipid fraction and its components, e. g. squalene, lanosterol and cholesterol, as well as into sterols precipitated by digitonin, showed that malonyl-CoA incorporation into the total non-saponified lipid fraction was more intensive than that of acetyl-CoA. However, acetyl-CoA was far more efficiently incorporated into sterols precipitated by digitonin or isolated by TLC than malonyl-CoA. The rate of acetyl-CoA incorporation into the total non-saponified lipid fraction and into squalene, lanosterol and cholesterol was maximal in the middle of the dark period and minimal in the middle of the light period. On the contrary, the rate of malonyl-CoA incorporation into these products was minimal in the middle of the dark period and maximal in the middle of the light period. The rate of fatty acid biosynthesis from acetyl-CoA was increased in the middle of the light and dark periods...
 ...
PMID:[Activities of 3-hydroxy-3-methylglutaryl-CoA reductase and acetyl-CoA carboxylase and rate of biosynthesis of mevalonic acid, squalene, sterols and fatty acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in rat liver: changes induced by daily rhythm]. 611 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>