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)

We have previously demonstrated that de novo fatty acid synthesis predominantly occurs in later phases of megakaryocyte maturation. Therefore we have investigated the expression of fatty acid synthase (FAS) and acetyl coenzyme A carboxylase (ACC), key enzymes for fatty acid synthesis in megakaryocytes at different phases of maturation. Immature and mature megakaryocytes were isolated. Guinea pig-specific FAS and ACC cDNA probes were prepared by reverse transcriptase reaction-polymerase chain reaction (RT-PCR). The probes were used to assess the expression of mRNA for ACC and FAS by Northern blotting. The hybrids were quantitated by densitometry. Endogenous megakaryocyte ACC was quantitated by virtue of its biotin content by Western blotting with streptavidin and enhanced chemiluminescence (ECL). The ratio of ACC mRNA between mature and immature megakaryocytes was 2.43 +/- 0.86, and the ratio of FAS mRNA was 0.50 +/- 0.13 (mean +/- SD, n = 4). The ratio of endogenous ACC in mature and immature megakaryocytes was 1.96 +/- 0.62 (n = 6). The study showed that the FAS mRNA was expressed in all phases of megakaryocyte maturation. However, both mRNA for ACC and endogenous ACC were demonstrated primarily in mature megakaryocytes. Thus de novo fatty acid synthesis in megakaryocytes may depend on the expression of ACC in mature cells. The expression of ACC occurs during the terminal phases of megakaryocyte maturation and may be a marker of megakaryocyte maturity.
 ...
PMID:The expression of acetyl coenzyme A carboxylase is related to megakaryocyte maturation. 763 91

The relative contributions of increased hepatic secretion of triglyceride (TG) and decreased TG catabolism to hypertriglyceridemia in the nephrotic syndrome, and their relationship to urinary protein loss and reduced plasma colloid osmotic pressure (pi) remain unclear. We measured the activity of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), two key enzymes of fatty acid synthesis in hepatic cytosol, in fed control rats, in rats with congenital analbuminemia (NA) that are free of proteinuria, and in rats with adriamycin-induced nephrotic syndrome (ADR). Both NA and ADR rats had decreased pi (respectively 13.2 +/- 0.3 and 10.7 +/- 0.4 mm Hg vs. control rats 18.3 +/- 0.7 mm Hg, P < 0.05), but only ADR rats had increased plasma TG (5.8 +/- 2.6 mmol/liter vs. 1.5 +/- 0.2 mmol/liter in both control and NA rats, P < 0.05), and were proteinuric: 811 +/- 45 mg/day, P < 0.01 versus control and NA rats. Total cytosolic ACC activity, expressed per g body weight, was increased in both NA and ADR rats by 45% and 39%, respectively (P < 0.05). Total FAS activity was increased by 65% and 115% in NA and ADR rats, respectively (P < 0.05). Thus low pi was consistently associated with an increase in total ACC and FAS activities in the livers of fed rats. However, low pi was consistently associated with an increase in plasma TG only in ADR rats. Hepatic TG secretion rates, measured in vivo after blocking lipolysis with Triton WR-1339 in fasting animals, were increased by 33% in both ADR and NA rats as compared to controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion. 772 42

In previous studies, zinc-deficient rats force-fed a diet with coconut oil as the major dietary fat developed a fatty liver, whereas zinc-deficient rats force-fed a diet with linseed oil did not. The present study was conducted to elucidate the reason for this phenomenon. In a bifactorial experiment, rats were fed zinc-adequate or zinc-deficient diets containing either a mixture of coconut oil (70 g/kg) and safflower oil (10 g/kg) ("coconut oil diet") or linseed oil (80 g/kg) ("linseed oil diet") as a source of dietary fat, and activities of lipogenic and glycolytic enzymes in liver were determined. In order to ensure adequate food intake, all the rats were force-fed. Zinc-deficient rats on the coconut oil diet developed a fatty liver, characterized by elevated levels of triglycerides with saturated and monounsaturated fatty acids. These rats also had markedly elevated activities of the lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and citrate cleavage enzyme, whereas activities of malic enzyme and glycolytic enzymes were not different compared with zinc-adequate rats on the coconut oil diet. In contrast, rats receiving the linseed oil diet had similar triglyceride concentrations regardless of zinc status, and activities of lipogenic enzymes and glycolytic enzymes were not different between the two groups. Zinc-deficient rats fed either type of dietary fat exhibited statistically significant correlations between activities of FAS, G6PDH, 6PGDH and concentrations of saturated and monounsaturated fatty acids in liver.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Zinc deficiency and activities of lipogenic and glycolytic enzymes in liver of rats fed coconut oil or linseed oil. 776 Jun 90

1. Chronic alcohol feeding with a low-fat diet (4.4% total calories) produced a two- to three-fold increase in hepatic triacylglycerol and esterified cholesterol compared with pair-fed low-fat diet controls. Plasma lipids were similar in both groups. 2. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were significantly lower in the alcohol-fed animals than in controls. Activities of hepatic fatty acid synthase (EC 2.3.1.85) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced in the alcohol-fed rats. 3. These results indicate that enhanced hepatic fatty acid synthesis does not occur in rats fed alcohol and a low-fat diet for 4 weeks, and is thus not implicated in the pathogenesis of alcohol-induced fatty liver.
 ...
PMID:Fatty acid synthesis by rat liver after chronic ethanol feeding with a low-fat diet. 783 97

Vanadium is a potent insulinomimetic agent. In vivo, its blood glucose lowering action in insulin-deficient diabetic rats is associated with corrected expression of genes involved in hepatic glucose metabolism. In this study, we investigated whether vanadate treatment also reverses the impaired expression of genes coding for key enzymes of lipogenesis in diabetic liver and white adipose tissue. Oral administration of vanadate to streptozotocin-rats caused a 55% fall in plasma glucose levels after feeding without modifying low insulinaemia. It also partially corrected the low thyroid hormone concentrations. In untreated diabetic animals, hepatic mRNA levels of acetyl-CoA carboxylase and fatty acid synthase were reduced by more than 80 and 90%, respectively, in close correlation with changes in enzyme activities. Three weeks of vanadate treatment totally restored acetyl-CoA carboxylase mRNA and partially restored fatty acid synthase mRNA (71% of control levels). The activities of both lipogenic enzymes were increased 3.5 to 4-fold, to reach 45 to 65% of control values. By contrast, in white adipose tissue, vanadate modified neither expression nor activity of both lipogenic enzymes, which remained blunted (< 10% of control levels). In conclusion, vanadate treatment partially restores the activities of two key lipogenic enzymes in liver, but not in white adipose tissue, of diabetic rats. This correction results from a reversal of impaired pre-translational regulatory mechanisms possibly mediated by an improvement of thyroid function and a selective restoration of liver glycolytic flux.
 ...
PMID:Tissue-specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate. 786 78

In vivo and in vitro experiments strongly support the view that marked increases in the levels of mRNA and in the activities of lipogenic enzymes that occur in liver and white adipose tissue of the rat after weaning to a high-carbohydrate diet are dependent on an increase in plasma glucose and insulin concentrations. An increased glucose metabolism is necessary for the expression of insulin effects on fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) mRNA accumulation in white adipose tissue, as insulin is ineffective in vitro in the absence of glucose. It is suggested that intracellular glucose-6-phosphate could play an important role in the effect of insulin on lipogenic enzyme gene expression in white adipose tissue. Other hormones and substrates could also play a role in the surge of lipogenesis after weaning. The fall in plasma glucagon after weaning to a high-carbohydrate diet could reinforce the insulin-induced accumulation of FAS and ACC mRNA, as this hormone inhibits the accumulation of lipogenic enzyme mRNA in liver and white adipose tissue. The decrease in the dietary supply of fat after weaning to a high-carbohydrate diet could also potentiate the accumulation of FAS and ACC mRNA in liver because long-chain poly-unsaturated fatty acids are potent inhibitors of the expression of the genes encoding liver lipogenic enzymes. A direct effect of fatty acids on a cis-acting element of the lipogenic enzyme genes could be involved, as the regulatory region of FAS gene contains a polyunsaturated fatty acid response element that shares some similarity with the peroxisome proliferator-activated receptor recently described.
 ...
PMID:Regulation of lipogenic enzyme gene expression by nutrients and hormones. 790 48

The in vitro and in vivo effects of lovastatin on fatty acid metabolism were studied in isolated rat hepatocytes. When added in vitro to cell incubations, lovastatin stimulated de novo fatty acid synthesis and acetyl-CoA carboxylase activity, whereas fatty acid synthase activity was unaffected. Lovastatin depressed palmitate, but not octanoate, oxidation. This may be attributed to the lovastatin-induced increase in intracellular malonyl-CoA levels, as no concomitant change of carnitine palmitoyltransferase I (CPT-I) specific activity was detected. Lovastatin had no effect on the synthesis and secretion of triacylglycerols and phospholipids in the form of very low density lipoproteins (VLDL). When rats were fed a diet supplemented with 0.1% (w/w) lovastatin for one week, both acetyl-CoA carboxylase activity and de novo fatty acid synthesis were reduced compared to pair-fed controls, whereas fatty acid synthase activity was unaffected. Palmitate oxidation was enhanced in the lovastatin-fed group. There was an increase in CPT-I activity but no change in intracellular concentration of malonyl-CoA. Lovastatin feeding had no significant effect either on the esterification of exogenous palmitic acid into both cellular and VLDL triacylglycerols and phospholipids or on hepatic lipid accumulation. The in vitro and in vivo effects of lovastatin were not significantly different between periportal and perivenous hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of lovastatin on hepatic fatty acid metabolism. 790 61

We describe the construction of ribozyme genes that are specific to acetyl-CoA carboxylase [ACC; acetyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] mRNAs and the effects of their expression on long-chain fatty acid synthesis. In a cell-free system, these ribozymes precisely cleave ACC mRNA at the expected sites. 30A5 preadipocyte cells stably transfected with the ribozyme gene show a substantial reduction in the amount of ACC mRNA as compared to non-ribozyme-expressing cells. The decrease in ACC mRNA was associated with a significant decrease in ACC enzyme activity, and the rate of fatty acid synthesis fell to about 30-70% of the control. When these cells are induced to differentiate into adipocytes, lipid accumulation is very slow in comparison with control cells. The activity of fatty acid synthase and the mRNA level of beta-actin were not affected. These data indicate that ribozymes designed to specifically target ACC mRNA under in vivo conditions act by decreasing the ACC mRNA level, which, in turn, decreases fatty acid synthesis.
 ...
PMID:Inhibition of fatty acid synthesis by expression of an acetyl-CoA carboxylase-specific ribozyme gene. 793 24

1. Using the polymerase chain reaction we have isolated a partial complementary DNA for goat acetyl-CoA carboxylase which is 90 and 82% homologous to the published rat and chicken complementary DNA sequences, respectively. 2. Frequent milking causes an upregulation of the acetyl-CoA carboxylase and fatty acid synthase genes in goat mammary gland that parallels the increase in the respective enzyme activities. 3. The sequence for goat acetyl-CoA carboxylase is in the EMBL data base, Accession Number Z17803.
 ...
PMID:Isolation of a goat acetyl-CoA carboxylase complementary DNA and effect of milking frequency on the expression of the acetyl-CoA carboxylase and fatty acid synthase genes in goat mammary gland. 809 21

Hepatocytes isolated from 9-week-old chickens were cultured in a serum-free, hormonally defined medium. Relative amounts of mRNAs coding for lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, delta 9 desaturase, malic enzyme) and apoproteins (apoprotein A1 and apoprotein B) were determined until the 12th day. beta-actin and albumin mRNA, as well as albumin secretion, were also assessed. Cellular metabolic activity appeared to be very low for the first days of culture, but increased after the 7th day. All the mRNAs studied, except for that of malic enzyme, were present from this time throughout the culture lifespan. The biological significance of the observed results and the relevance of this chicken hepatocyte culture system for long-term metabolic and genetic studies are discussed.
 ...
PMID:Lipogenic enzyme and apoprotein messenger RNAs in long-term primary culture of chicken hepatocytes. 810 Feb 36


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