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)

1. Carcase composition, fat deposition and the activities of three liver lipogenic enzymes were compared in turkeys and chickens fed ad libitum on two different isocaloric diets, respectively adapted to chickens (C) and to turkeys (T). Diets differed in their protein content, being higher by 60 g/kg in diet T. 2. Chickens were much fatter than turkeys and exhibited higher activities of acetyl-coenzyme A carboxylase (EC 6.4.1.2) and malic enzyme (EC 1.1.1.40). 3. The carcase composition of turkeys was not influenced by the type of diet administered, while chickens fed on diet C were fatter than chickens fed on diet T. Compared to diet T, diet C enhanced malic enzyme activity, whatever the species and age. 4. A good correlation between abdominal fat and total fatness was observed in both species but especially in turkeys. 5. In conclusion, hepatic lipogenesis is much lower in turkeys than in chickens.
Br Poult Sci 1992 Dec
PMID:Lipogenesis in turkeys and chickens: a study of body composition and liver lipogenic enzyme activities. 136 22

Rapid inhibition of acetyl-CoA carboxylase (ACC) activity in rat liver in response to 6 h starvation and rapid re-activation in response to 2-6 h of re-feeding chow were shown to be due to changes in the expressed activity of existing enzyme. Decreases and increases in ACC concentration occurred at later stages of the transitions, i.e. 6-48 h starvation and 8-24 h re-feeding respectively. The decrease in expressed activity of ACC was due primarily to changes in its phosphorylation state, demonstrated by a significantly decreased Vmax. and significantly increased Ka for citrate of enzyme purified by avidin-Sepharose chromatography from 6 h- or 48 h-starved rats. These effects were totally reversed within 2-4 h of chow re-feeding. Changes in the activity of purified ACC closely correlated with reciprocal changes in the activity of AMP-activated protein kinase (AMP-PK) over the fed to starved to re-fed transition. Increases in the activity ratio of cyclic-AMP-dependent protein kinase in response to starvation lagged behind the increase in AMP-PK and the decrease in ACC activity. Changes in AMP-PK and ACC activities of rat liver closely correlated with changes in plasma insulin concentration in response to time courses of starvation and re-feeding.
Biochem J 1991 Dec 15
PMID:The short-term regulation of hepatic acetyl-CoA carboxylase during starvation and re-feeding in the rat. 168 93

Acetyl-CoA carboxylase (ACC) can be regulated in vitro via phosphorylation by a 5'-AMP-activated protein kinase. A potential intracellular role for this kinase has been studied in the Fao hepatoma cell by manipulating the intracellular adenine nucleotide pool with ATP-depleting agents. Three different ATP depletors, antimycin A, dinitrophenol, and sodium azide, all promote the rapid loss of ACC activity characterized by a marked reduction in enzyme Vmax, abolition of citrate-independent activity, an increase in the Ka for citrate and a reduction in the mass of a complex between the two major ACC isozymes. These effects persist through enzyme purification on monomeric avidin-Sepharose and are accompanied by an increase in 32P-content, both consistent with depletor-induced covalent enzyme modification. The effects of ATP depletors in intact cells are mimicked in vitro on phosphorylation of ACC by the 5'-AMP-activated protein kinase and are reversible on dephosphorylation. These data indicate that ACC activity is sensitive to the intracellular adenylate charge, but that changes in the state of enzyme phosphorylation, rather than direct allosteric regulation by adenine nucleotides, underly this mode of enzyme control. This kinase-mediated modulation provides a mechanism for altering the rate of fatty acid synthesis and, secondarily, fatty acid oxidation, depending on the rate of ATP generation from carbohydrate-derived precursors in several tissues in vivo.
Biochem Biophys Res Commun 1991 Dec 31
PMID:Regulation of intracellular acetyl-CoA carboxylase by ATP depletors mimics the action of the 5'-AMP-activated protein kinase. 168 96

This article reviews current knowledge concerning the dermatologic manifestations of biotin deficiency. Biotin is a water-soluble vitamin that acts as an essential cofactor for four carboxylases, each of which catalyzes an essential step in intermediary metabolism. For example, acetyl-CoA carboxylase catalyzes the rate-limiting step in fatty acid elongation. In infants, children, and adults, deficiency of biotin causes alopecia and a characteristic scaly, erythematous dermatitis distributed around body orifices. The rash closely resembles that of zinc deficiency. Candida albicans often can be cultured from the skin lesions. Biotinidase deficiency, an inborn error, causes biotin deficiency, probably as a consequence of unpaired intestinal absorption, cellular salvage, and renal reclamation of biotin; biotinidase deficiency causes dermatologic manifestations similar to biotin deficiency. There is evidence that impaired fatty acid metabolism secondary to reduced activities of the biotin-dependent carboxylases (especially acetyl-CoA carboxylase) plays an etiologic role in the dermatologic manifestations of biotin deficiency. Candida infections secondary to impaired immune function might also contribute to the dermatitis of biotin deficiency.
Semin Dermatol 1991 Dec
PMID:Skin manifestations of biotin deficiency. 176 57

Biotin uptake, utilization, and efflux were studied in normal and biotin-deficient cultured rat hepatocytes. Biotin-deficient cells accumulate about 16-fold more biotin than do normal cells when incubated with a physiological concentration of biotin for 24 h. This difference is due to the greater amount of protein-bound biotin relative to free biotin in biotin-deficient hepatocytes, and is attributable to the presence of more apocarboxylases in deficient cells. The rate of biotin uptake and the rate of activation of the carboxylases, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase, are proportional to the concentration of exogenous biotin. Increases in carboxylase activities are proportional to the concentration of biotin only at exogenous biotin concentrations of less than 410 nM. Concentrations of 410 nM or more biotin increase carboxylase activities to normal or near normal. Biocytin inhibits biotin uptake at very high concentrations, whereas desthiobiotin and lipoic acid have no effect. Biocytin in the medium results in carboxylase activation either intracellularly or extracellularly by conversion to biotin by biotinidase. Investigation of the efflux of biotin from normal and biotin-deficient cells preincubated with the vitamin showed greater retention of biotin by biotin-deficient cells than by normal cells over 24 h. Retention of free biotin is similar in biotin-deficient and normal cells. The greater amount of biotin retained by biotin-deficient cells is accounted for by the greater amount of bound biotin in these cells. These results suggest that the free and bound biotin pools are independently regulated. The ready loss of free biotin from these cells has implications for the treatment of inherited, biotin-responsive carboxylase deficiencies.
Biochem Med Metab Biol 1991 Dec
PMID:Biotin uptake, utilization, and efflux in normal and biotin-deficient rat hepatocytes. 179 12

Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Dec
PMID:Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. 197 29

We have used the cold-clamping technique to study the changes in acetyl-CoA carboxylase activity that occur in the cytosolic and mitochondrial fractions of the liver of fed, starved and starved-refed rats. No evidence was found for a role of the mitochondrial enzyme as a pool from which cytosolic carboxylase could be replenished upon refeeding of starved rats. Starvation for 24 h or 48 h induced changes in the expressed (assayed at 20 mM-citrate), total (citrate- and phosphatase-treated) and citrate-independent activities of cytosolic carboxylase, as well as in its Ka for citrate. The expressed/total activity ratio was low even in the fed state and was depressed further by starvation. The effects of refeeding occurred in two phases: an acute phase (approx. 1 h) in which the starvation-induced changes in Ka and expressed/total activity ratio were rapidly reversed, and a prolonged slow phase in which the two parameters attained values that were lower and higher, respectively, than those in the normal fed state. Refeeding also resulted in a gradual increase in citrate-independent activity of acetyl-CoA carboxylase. An additional marked increase in this activity occurred only in 48 h-starved-refed rats between 24 h and 48 h of refeeding. These findings are discussed in terms of the observed time courses of changes in lipogenic rates that occur in vivo in starved-refed rats and of the possible molecular mechanisms involved.
Biochem J 1990 Dec 01
PMID:Changes in the properties of cytosolic acetyl-CoA carboxylase studied in cold-clamped liver samples from fed, starved and starved-refed rats. 198 63

The relative amounts of mRNAs coding for fatty-acid synthase (EC 2.3.1.85), acetyl-CoA carboxylase (EC 6.4.1.2), ATP citrate lyase (EC 4.1.3.8) and malic enzyme (EC 1.1.1.40) were determined in lungs and livers of adult rats that were normally fed, starved for 48 h or starved for 48 h and subsequently refed for 72 h with a carbohydrate-rich, fat-free diet. In the liver, starvation caused a small decrease in the relative abundance of the mRNAs which was not statistically significant. Subsequent refeeding caused a statistically significant increase in mRNAs for all of the enzymes studied. In the lung, no significant changes were found, indicating that the regulation of the abundance of mRNAs encoding the lipogenic enzymes in the lung differs from that in the liver. In the developing rat lung, mRNA for fatty-acid synthase increased 3-fold in abundance between fetal days 18 and 20 and decreased directly after birth (at day 22 of gestation). A similar pattern was observed for ATP citrate lyase mRNA. The level of acetyl-CoA carboxylase mRNA decreased significantly after birth. These observations indicate that in perinatal rat lungs, pretranslational regulation is involved in the control of the synthesis of these enzymes. The abundance of acetyl-CoA carboxylase mRNA did not change in the prenatal period, a time during which the specific activity of this enzyme increases. This lack of correlation between the specific activity of acetyl-CoA carboxylase and the abundance of its mRNA may indicate that translational regulation of the synthesis of the enzyme or post-synthetic regulatory effects on enzyme molecules are involved in the control of this enzyme in the prenatal period. No changes in the abundance of lung malic enzyme mRNAs were observed throughout the perinatal period.
Biochim Biophys Acta 1989 Dec 18
PMID:Levels of mRNAs coding for lipogenic enzymes in rat lung upon fasting and refeeding and during perinatal development. 257 95

1. We have synthesized two peptides, one based on the exact sequence around the unique site (Ser79) for the AMP-activated protein kinase on rat acetyl-CoA carboxylase (SSMS peptide) and another in which the serine residue corresponding to the site for cyclic-AMP-dependent protein kinase (Ser77) was replaced by alanine (SAMS peptide). 2. Both peptides were phosphorylated with similar kinetics by the AMP-activated protein kinase, but only the SSMS peptide was a substrate for cyclic-AMP-dependent protein kinase. The SAMS peptide was not phosphorylated by any of five other purified protein kinases tested. 3. The Km of AMP-activated protein kinase for the SAMS peptide is higher than that for acetyl-CoA carboxylase, but the Vmax for peptide phosphorylation is 2.5 times higher than that of its parent protein. This peptide therefore gives a convenient and sensitive assay for the AMP-activated protein kinase. 4. Acetyl-CoA-carboxylase kinase and peptide kinase activities copurify through six steps from a post-mitochondrial supernatant of rat liver, showing that the SAMS peptide is a specific substrate for the AMP-activated protein kinase in this tissue. We could not demonstrate AMP-dependence of the kinase activity in crude preparations, apparently due to endogenous AMP remaining bound to the enzyme. However, 8-bromoadenosine 5-monophosphate (Br8AMP) is a partial agonist at the allosteric (AMP) site, and inhibition by 2 mM Br8AMP can be used to test that one is measuring the AMP-stimulated form of the kinase. 5. Using this approach, we have examined the kinase activity in nine different rat tissues, plus a mouse macrophage cell line, and find that there is a correlation between tissues expressing significant levels of peptide kinase activity and those active in the synthesis or storage of lipids. 6. We also use the peptide assay to show that cyclic AMP-dependent protein kinase does not activate purified AMP-activated protein kinase, and does not affect the activation of partially purified AMP-activated protein kinase by endogenous kinase kinase.
Eur J Biochem 1989 Dec 08
PMID:Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay. 257 67

I describe a general and rapid procedure allowing the isolation of specialized lambda transducing phages from a lambda library by lysogenic complementation of defective mutants of Escherichia coli. As an example, the cloning of the E. coli fabE gene and of two other adjacent genetic determinants is presented. Subcloning and determination of its nucleotide sequence reveals that fabE codes for the biotin carboxyl carrier protein (BCCP), one of the three subunits of acetyl coenzyme A carboxylase.
DNA 1989 Dec
PMID:A rapid procedure for cloning genes from lambda libraries by complementation of E. coli defective mutants: application to the fabE region of the E. coli chromosome. 257 89


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