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)

Acetyl-CoA carboxylase, the rate-limiting enzyme in the biogenesis of long-chain fatty acids, is regulated by phosphorylation and dephosphorylation. The major phosphorylation sites that affect carboxylase activity and the specific protein kinases responsible for phosphorylation of different sites have been identified. A form of acetyl-CoA carboxylase that is independent of citrate for activity occurs in vivo. This active form of carboxylase becomes citrate-dependent upon phosphorylation under conditions of reduced lipogenesis. Therefore, phosphorylation-dephosphorylation of acetyl-CoA carboxylase is the enzyme's primary short-term regulatory mechanism; this control mechanism together with cellular metabolites such as CoA, citrate, and palmitoyl-CoA serves to fine-tune the synthesis of long-chain fatty acids under different physiological conditions.
FASEB J 1989 Sep
PMID:Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. 257 Jul 25

A protein kinase, termed microtubule-associated protein (MAP) kinase, which phosphorylates microtubule-associated protein 2 (MAP-2) in vitro and is stimulated 1.5-3-fold in extracts from insulin-treated 3T3-L1 cells has been identified (Ray, L.B., and Sturgill, T.W. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1502-1506). Here, we describe chromatographic properties of MAP kinase and provide biochemical characterization of the partially purified enzyme. Isolation of the enzyme is facilitated by its unusually high affinity for hydrophobic interaction chromatography matrices. The molecular weight of the partially purified enzyme was determined to be 35,000 by gel filtration chromatography and 37,000 by glycerol gradient centrifugation. MAP kinase activity of chromatographic fractions correlated precisely with the presence of a 40-kDa phosphoprotein detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. MAP kinase has a Km of 7 microM for ATP and does not utilize GTP. Acetyl-CoA carboxylase, ATP citrate-lyase, casein, histones, phosvitin, protamine, and ribosomal protein S6 were all poor substrates relative to MAP-2. The enzyme is inhibited by fluoride and beta-glycerol phosphate but not by heparin. These properties of MAP kinase distinguish it from protein kinases previously described in the literature.
J Biol Chem 1988 Sep 05
PMID:Characterization of insulin-stimulated microtubule-associated protein kinase. Rapid isolation and stabilization of a novel serine/threonine kinase from 3T3-L1 cells. 284 41

A procedure to detect biotinyl proteins after fractionation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was developed. Proteins were immobilized on nitrocellulose and biotin-containing proteins were detected by probing with 125I-streptavidin. Using this procedure a small survey of biotinyl protein in plants was undertaken. In total four biotin-containing proteins were detected in higher plants of molecular weights 62,000, 50,000, 34,000, and 31,000. These biotinyl proteins were not ubiquitous in the plants surveyed. In the cyanobacterium Anabeana variabilis, a single biotin-containing protein of 21,000 Da was detected. In isolated spinach chloroplasts, the two biotinyl proteins detected were soluble. The results are discussed in relation to acetyl-CoA carboxylase.
Anal Biochem 1985 Sep
PMID:Use of streptavidin to detect biotin-containing proteins in plants. 286 33

When fasted rats were refed for 4 days with a carbohydrate and protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate), the effects of dietary nutrients on the fatty acid synthesis from injected tritiated water, the substrate and effector levels of lipogenic enzymes and the enzyme activities were compared in the livers. In the carbohydrate diet group, although acetyl-CoA carboxylase was much induced and citrate was much increased, the activity of acetyl-CoA carboxylase extracted with phosphatase inhibitor and activated with 0.5 mM citrate was low in comparison to the carbohydrate and protein diet group. The physiological activity of acetyl-CoA carboxylase seems to be low. In the protein diet group, the concentrations of glucose 6-phosphate, acetyl-CoA and malonyl-CoA were markedly higher than in the carbohydrate and protein group, whereas the concentrations of oxaloacetate and citrate were lower. The levels of hepatic cAMP and plasma glucagon were high. The activities of acetyl-CoA carboxylase and also fatty acid synthetase were low in the protein group. By feeding fat, the citrate level was not decreased as much as the lipogenic enzyme inductions. Comparing the substrate and effector levels with the Km and Ka values, the activities of acetyl-CoA carboxylase and fatty acid synthetase could be limited by the levels. The fatty acid synthesis from tritiated water corresponded more closely to the acetyl-CoA carboxylase activity (activated 0.5 mM citrate) than to other lipogenic enzyme activities. On the other hand, neither the activities of glucose-6-phosphate dehydrogenase and malic enzyme (even though markedly lowered by diet) nor the levels of their substrates appeared to limit fatty acid synthesis of any of the dietary groups. Thus, it is suggested that under the dietary nutrient manipulation, acetyl-CoA carboxylase activity would be the first candidate of the rate-limiting factor for fatty acid synthesis with the regulations of the enzyme quantity, the substrate and effector levels and the enzyme modification.
Biochim Biophys Acta 1986 Sep 12
PMID:Effects of dietary nutrients on substrate and effector levels of lipogenic enzymes, and lipogenesis from tritiated water in rat liver. 287 38

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.
Biochem Biophys Res Commun 1986 Sep 14
PMID:No synergism between ionomycin and phorbol ester in fatty acid synthesis by isolated rat hepatocytes. 287 2

Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats.
Biochem J 1986 Sep 01
PMID:Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat. 287 33

Although lipogenic enzyme inductions are reduced by fat feeding, this reduction decreases with aging and is particularly detectable in the case of acetyl-CoA carboxylase and fatty acid synthetase activities. On the other hand, the fat-dependent reductions of malic enzyme and acetyl-CoA carboxylase were consistently relieved by triiodothyronine (T3) treatment. The effects of T3 treatment on these enzyme inductions were greater in 10-month-old rats than in 1-month-old rats, while the carbohydrate-dependent induction and the fat-dependent reduction of the enzymes decreased with aging. In these animals, alterations in malic enzyme mRNA translational activities were roughly in parallel to the enzyme activities. Therefore, the age-dependent alterations in effects of T3 treatment and fat on malic enzyme induction do not appear to occur in post-translation.
Biochim Biophys Acta 1987 Sep 04
PMID:Effects of aging on contributions of dietary fat and triiodothyronine treatment to lipogenic enzyme induction. 288 7

Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting and/or first committed step in fatty acid biosynthesis. Because fatty acids must be synthesized as components of the galactolipids and phospholipids in myelin, high specific activities of ACC would be expected in brain during myelination and in the myelinating cells, the oligondendroglia, in particular. Under reaction conditions where ACC was linear with time and protein concentration, we found specific activities of 1.7 and 3.1 nmol/min/mg protein in supernatants from forebrains and brainstems, respectively, of 20-day-old rats. In both regions, ACC declined during development, particularly after the age of 20 days. To separate forebrain into discrete fractions containing cells, membrane vesicles, and other components, without destroying the ACC, it was necessary to modify the published methods by adding citrate to the isolation medium and by omitting trypsin. A fraction which sedimented over 1.2 M sucrose showed the highest specific activities and recoveries of ACC. This fraction was rich in small cells, many of which immunostained with antibodies against galactocerebroside and carbonic anhydrase, both of which are localized in oligodendrocytes and immature glial cells. The cells in this fraction also immunostained with antibodies against ACC. The results are consistent with the hypothesis that ACC is an oligodendrocyte-associated enzyme, although it probably is not exclusive to cells of that type.
Brain Res 1988 Sep 01
PMID:Acetyl-CoA carboxylase in rat brain. I. Activities in homogenates and isolated fractions. 290 26

Acetyl-CoA carboxylase (ACC) catalyzes the first and, possibly, the rate-limiting step in fatty acid biosynthesis. Because oligodendrocytes must synthesize large amounts of lipid during myelination, the hypothesis was proposed that ACC might be localized in cells of that type. In sections from the brains of 12-day-old rats, ACC immunostaining was observed in glial cells in white matter and gray matter. These cells resembled carbonic anhydrase-positive oligodendrocytes at mature and immature stages of their development. Cells resembling typical oligodendrocytes were also ACC-positive in white matter from the forebrains and brainstems of 15-17 day-old-rats. In both the gray matter and the white matter of 21-day-old rats there were intensely ACC-positive cells that strongly resembled oligodendrocytes. Oligodendrocytes in the brains of adult rats also were ACC-positive. While recognizing that some ACC must be present at lower levels in other types of cells and at all ages, it was concluded that the present findings are consistent with its primary locus as the oligodendrocytes, particularly during myelination. Further, enrichment of ACC and carbonic anhydrase in the same type of cell suggested that carbonic anhydrase might serve in providing a substrate, bicarbonate, to be utilized by ACC.
Brain Res 1988 Sep 01
PMID:Acetyl-CoA carboxylase in rat brain. II. Immunocytochemical localization. 290 27

We have examined the activity of three lipogenic enzymes [malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PD), and acetyl coenzyme A (CoA) carboxylase], the activity of the mitochondrial FAD-dependent alpha-glycerolphosphate dehydrogenase (alpha-GPD), and the mitochondrial concentration of uncoupling protein (UCP) in brown adipose tissue (BAT) of euthyroid and hypothyroid rats, both at room temperature and in response to acute cold stress. These enzymes and UCP are important for the thermogenic response of BAT in adaptation to cold. The basal level of the lipogenic enzymes was normal or slightly elevated in hypothyroid rats maintained at 23 degrees C, but the levels of alpha-GPD and UCP were markedly reduced. Forty-eight hours at 4 degrees C resulted in an increase in the activity of G-6-PD, acetyl-CoA carboxylase, and alpha-GPD and in the concentration of UCP both in euthyroid and hypothyroid animals, but the levels reached were invariably less in hypothyroid animals, indicating that thyroid hormone is necessary for a full metabolic response of BAT under maximal demands. Of all variables measured, the most affected was UCP (only one-fifth of the response of euthyroid rats to cold) followed by alpha-GPD (approximately 50% the euthyroid response). The administration of replacement doses of triiodothyronine (T3) to hypothyroid rats for 5-7 days did not normalize any of the BAT responses, whereas the replacement of thyroxine (T4) for only 2 days sufficed to normalize them all. This effect of T4 was abolished by preventing its conversion to T3 with iopanoic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Physiol 1987 Sep
PMID:Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation. 363 Dec 56


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