Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The possible role played by albumin in regulating brain metabolism during development has been studied. The effects of fatty acid-free BSA on lactate, glucose, 3-hydroxybutyrate, and glutamine oxidation and lipogenesis by rat neurons and astrocytes from primary culture were studied. The rate of lactate oxidation and lipogenesis by neurons and astrocytes in the presence of BSA greatly exceeded that observed for glucose, 3-hydroxybutyrate, or glutamine, suggesting that lactate may be a key substrate for brain development. BSA strongly stimulated the rate of lactate, 3-hydroxybutyrate, and glutamine incorporation into lipids in both neurons (677%, 726%, and 250%, respectively) and astrocytes (415%, 393%, and 215%, respectively), possibly by binding long-chain acyl-CoA excesses, potent inhibitors of acetyl-CoA carboxylase. However, BSA decreased the rate of lipogenesis from glucose in both neurons (34%) and astrocytes (55%), probably by inhibiting glycerol-borne phospholipid synthesis. BSA significantly increased the rates of lactate (61%) and glucose (32%) oxidation by astrocytes but not those of 3-hydroxybutyrate and glutamine, suggesting that BSA may stimulate pyruvate oxidation. However, in neurons BSA did not affect the rate of oxidation of any of the substrates tested, which suggests that pyruvate oxidation is regulated differently in neurons and astrocytes. The results suggest that lactate is the most important substrate for both neurons and astrocytes, stressing the role played by lactate in brain development. Our results also suggest that serum albumin may control brain development by fostering metabolism for growth and differentiation purposes.
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PMID:Regulation of lactate metabolism by albumin in rat neurons and astrocytes from primary culture. 810 80

Prodigiosin 25-C had little effect on DNA, RNA, and protein synthesis, and cellular ATP content, but the drug markedly inhibited the incorporation of acetate into lipid fractions. Under the same conditions, the incorporation of other lipid precursors including glycerol, mevalonate, palmitate, and oleate was not affected. A decrease in the incorporation of acetate was not due to the inhibition of fatty acid biosynthesis, because prodigiosin 25-C did not affect the activity of acetyl-CoA synthetase, acetyl-CoA carboxylase or fatty acid synthase in cell-free assay systems prepared from rat liver cytosol. In contrast, prodigiosin 25-C strongly inhibited the rapid uptake of acetate into acid-soluble fraction in intact cells. The results suggest that prodigiosin 25-C specifically perturbs the permeation of acetate through plasma membranes.
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PMID:Prodigiosin 25-C perturbs permeation of acetate in a cultured cell line. 853 81

1. We have examined the interaction between aerobic exercise and lipid-lowering drugs in a crossover study of 16 healthy normolipidaemic volunteers who each received 21 days' treatment with bezafibrate (400 mg), fluvastatin (40 mg), and placebo, in random order. 2. Fluvastatin treatment reduced pre-exercise total cholesterol (TC) by 23% (P < 0.0001), low-density lipoprotein cholesterol (LDL-C) by 33% (P < 0.0001), and plasma triglycerides by 11%, compared with pre-treatment values. Bezafibrate reduced TC by 11% (P < 0.01); LDL-C by 9%; and plasma triglycerides by 40% (P < 0.01), compared with pre-treatment values. 3. During exercise, in comparison with placebo, and fluvastatin treatment, respectively, bezafibrate significantly reduced mean fat oxidation: 31% vs 39%, P = 0.035, 31% vs 39%, P = 0.002, plasma free fatty acid (FFA) availability, e.g. after 90 min of exercise: (t90) 520 vs 662 mumol 1(-1), P = 0.054, 520 vs 725 mumol 1(-1), P = 0.016, and plasma levels of glycerol (t90): 59 vs 74 mumol 1(-1), P = 0.037, 59 vs 73 mumol 1(-1), P = 0.016. Fluvastatin had no impact on fat metabolism in comparison with placebo. 4. Reduced plasma FFA concentration and lower fat oxidation during prolonged exercise on bezafibrate treatment may be due to an inhibition of hepatic acetyl coenzyme A carboxylase, resulting in reduced FFA release from adipose tissue. 5. The possibility that impaired fat metabolism on fibrates could induce premature fatigue during exercise of moderate duration and intensity should be examined in hyperlipidaemic patients.
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PMID:A comparison of the effects of fluvastatin and bezafibrate on exercise metabolism: a placebo-controlled study in healthy normolipidaemic subjects. 873 78

In order to study the problem of how the biomembrane synthesis started in the evolutionary process of the self-reproducing system, we carry out an extensive similarity search of the sequence data stored in databases, using the acetyl-CoA carboxylase, fatty acid synthase and the enzyme proteins leading to the combination of sn-glycerol 3-phosphate and fatty acid as the query sequences. With the use of the FASTA program (Pearson & Lipman, 1988), the proteins that carry an amino acid sequence showing similarity to any of the query sequences are picked up under the criterion of statistical significance of more than 6.0 for the homology, then classified according to the functional blocks where they operate. Finally they are filtered to the enzyme proteins in the metabolic pathways and to the DNA- or RNA-interacting proteins in the translation, transcription and replication apparatuses by eliminating proteins such as membrane proteins, lipase etc. which seem to have been generated after the appearance of the biomembrane. The distribution of the proteins thus selected shows a clear pattern that the amino acid sequences showing considerable similarity to the biomembrane synthetic proteins are concentrically found in the enzyme proteins in and around the section of glycolytic pathway from glyceraldehyde 3-phosphate to pyruvate while the DNA- or RNA-interacting proteins similar to the query sequences are distributed sparsely over the translation, transcription and replication systems. The assignment of similarity regions ascertains that considerable regions of most biomembrane synthetic proteins are covered by the enzyme proteins in and around the glycolytic pathway. Although acetyl-CoA carboxylase and fatty acid synthase are full of variety in the constitution of active domains depending on species, the above-mentioned pattern is also obtained by using either the monofunctional or the multifunctional type of proteins as the query sequences. Thus, the evolution towards biomembrane synthesis may be positioned as an event following the establishment of a section of glycolytic pathway from glyceraldehyde 3-phosphate to pyruvate. The causality of this evolution from the glycolytic pathway to the biomembrane synthesis is also discussed in connection with the absorption of protons released in the glycolytic process.
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PMID:Evolution of the self-reproducing system to the biosynthesis of the membrane: an approach from the amino acid sequence similarity in proteins. 894 44

Adaptation of rats to a high-protein, carbohydrate-free (HP) diet induced a marked reduction of brown adipose tissue (BAT) fatty acid (FA) synthesis from both 3H2O and [14C]glucose in vivo, with pronounced decreases in the activities of four enzymes associated with lipogenesis: glucose-6-phosphate dehydrogenase, malic enzyme, citrate lyase, and acetyl-CoA carboxylase. In both HP-adapted and control rats, in vivo incorporation of 3H2O and [14C]glucose into BAT glyceride-glycerol was much higher than into FA. It could be estimated that most of the glycerol synthetized was used to esterify preformed FA. Glycerol synthesis from nonglucose sources (glyceroneogenesis) was increased in BAT from HP rats, as evidenced by an increased capacity of tissue fragments to incorporate [1-14C]pyruvate into glycerol and by a fourfold increase in the activity of phosphoenolpyruvate carboxykinase activity, a key glyceroneogenic enzyme. The data suggest that high rates of glyceroneogenesis and of esterification of preformed FA in BAT from HP-adapted rats are essential for preservation of tissue lipid stores, necessary for heat generation when BAT is recruited in nonshivering thermogenesis.
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PMID:Brown adipose tissue triacylglycerol synthesis in rats adapted to a high-protein, carbohydrate-free diet. 1019 78

To elucidate the physiological role of sterol regulatory element-binding protein-1 (SREBP-1), the hepatic mRNA levels of genes encoding various lipogenic enzymes were estimated in SREBP-1 gene knockout mice after a fasting-refeeding treatment, which is an established dietary manipulation for the induction of lipogenic enzymes. In the fasted state, the mRNA levels of all lipogenic enzymes were consistently low in both wild-type and SREBP-1(-/-) mice. However, the absence of SREBP-1 severely impaired the marked induction of hepatic mRNAs of fatty acid synthetic genes, such as acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase, that was observed upon refeeding in the wild-type mice. Furthermore, the refeeding responses of other lipogenic enzymes, glycerol-3-phosphate acyltransferase, ATP citrate lyase, malic enzyme, glucose-6-phosphate dehydrogenase, and S14 mRNAs, were completely abolished in SREBP-1(-/-) mice. In contrast, mRNA levels for cholesterol biosynthetic genes were elevated in the refed SREBP-1(-/-) livers accompanied by an increase in nuclear SREBP-2 protein. When fed a high carbohydrate diet for 14 days, the mRNA levels for these lipogenic enzymes were also strikingly lower in SREBP-1(-/-) mice than those in wild-type mice. These data demonstrate that SREBP-1 plays a crucial role in the induction of lipogenesis but not cholesterol biosynthesis in liver when excess energy by carbohydrates is consumed.
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PMID:Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. 1058 67

Strain BR54 of Clostridium beijerinckii was derived from the wild type strain, NCIMB 8052, by mutagenesis with Tn1545 and selection for butanol tolerance. It harbours a single copy of Tn 1545 in a 435 bp intergenic region separating two convergently transcribed genes, accC and gldA. The former encodes biotin carboxylase (E.C.6.3.4.14), a subunit of acetyl-CoA carboxylase and the latter encodes glycerol dehydrogenase (E.C.1.1.1.6). Since Tn1545 generates outwardly directed transcripts from its right end, we considered the possibility that the transposon inserted in strain BR54 might affect the expression of the adjacent gldA gene. RT-PCR experiments revealed that the mutant, but not the wild type, contains antisense RNA corresponding to the gldA gene. Correlated with this, the level of glycerol dehydrogenase activity in the mutant was only 25% of that in the wild type when bacteria were grown with either glucose or glycerol as the fermentable substrate. We conclude that transcripts emerging from the right end of the conjugative transposon, Tn1545, can reduce the expression of the adjacent gldA gene by the generation of antisense RNA and that this is associated with a butanol-tolerant phenotype.
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PMID:Butanol tolerance of Clostridium beijerinckii NCIMB 8052 associated with down-regulation of gldA by antisense RNA. 1093 92

Two treatments, fasting/refeeding and administration of liver X receptor (LXR) agonists, elevate the mRNA for sterol regulatory element-binding protein-1c (SREBP-1c) and enhance lipid synthesis in liver. These treatments do not affect the mRNA for SREBP-1a, an alternative transcript from the same gene. Through homologous recombination, we eliminated the exon encoding SREBP-1c from the mouse genome, leaving the SREBP-1a transcript intact. On a normal diet, livers of SREBP-1c(-/-) mice manifested reductions in multiple mRNAs encoding enzymes of fatty acid and triglyceride synthesis, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). In contrast, SREBP-1c(-/-) livers showed a compensatory increase in hepatic SREBP-2 mRNA, accompanied by increased mRNA levels for cholesterol biosynthetic enzymes. In fasted/refed animals, ACC and FAS mRNAs rose, but not to the same extent as in wild-type livers. The refeeding-induced increase in SREBP-1c(-/-) mice was greater than in mice lacking SREBP cleavage-activating protein (SCAP), in which all nuclear SREBPs are absent. Thus, SREBP-2 and/or SREBP-1a can substitute partially for SREBP-1c in permitting an insulin-mediated increase in ACC and FAS mRNAs. In contrast, mRNAs for several other lipogenic enzymes (glucose-6-phosphate dehydrogenase, malic enzyme, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase-1) showed a complete failure of the normal inductive response to refeeding, indicating specific reliance on SREBP-1c. Moreover, these mRNAs, as well as multiple other lipogenic mRNAs, showed a markedly blunted response to the LXR agonist T090137, indicating an essential role of SREBP-1c in the LXR response.
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PMID:Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. 1178 83

The accumulation of intracellular triacylglycerol (TG) is highly correlated with muscle insulin resistance. However, it is controversial whether the accumulation of TG is the result of increased fatty acid supply, decreased fatty acid oxidation, or both. Because abnormal fatty acid metabolism is a key contributor to the pathogenesis of diabetes-related cardiovascular dysfunction, we examined fatty acid and glucose metabolism in hearts of insulin-resistant JCR:LA-cp rats. Isolated working hearts from insulin-resistant rats had glycolytic rates that were reduced to 50% of lean control levels (P < 0.05). Cardiac TG content was increased by 50% (P < 0.05) in the insulin-resistant rats, but palmitate oxidation rates remained similar between the insulin-resistant and lean control rats. However, plasma fatty acids and TG levels, as well as cardiac fatty acid-binding protein (FABP) expression, were significantly increased in the insulin-resistant rats. AMP-activated protein kinase (AMPK) plays a major role in the regulation of cardiac fatty acid and glucose metabolism. When activated, AMPK increases fatty acid oxidation by inhibiting acetyl-CoA carboxylase (ACC) and reducing malonyl-CoA levels, and it decreases TG content by inhibiting glycerol-3-phosphate acyltransferase (GPAT), the rate-limiting step in TG synthesis. The activation of AMPK also stimulates cardiac glucose uptake and glycolysis. We thus investigated whether a decrease in AMPK activity was responsible for the reduced cardiac glycolysis and increased TG content in the insulin-resistant rats. However, we found no significant difference in AMPK activity. We also found no significant difference in various established downstream targets of AMPK: ACC activity, malonyl-CoA levels, carnitine palmitoyltransferase I activity, or GPAT activity. We conclude that hearts from insulin-resistant JCR:LA-cp rats accumulate substantial TG as a result of increased fatty acid supply rather than from reduced fatty acid oxidation. Furthermore, the accumulation of cardiac TG is associated with a reduction in insulin-stimulated glucose metabolism.
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PMID:Potential mechanisms and consequences of cardiac triacylglycerol accumulation in insulin-resistant rats. 1246 81

Glucose uptake into adipose and liver cells is known to up-regulate mRNA levels for various lipogenic enzymes such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). To determine whether the hexosamine biosynthesis pathway (HBP) mediates glucose regulation of mRNA expression, we treated primary cultured adipocytes for 18 h with insulin (25 ng/ml) and either glucose (20 mm) or glucosamine (2 mm). A ribonuclease protection assay was used to quantitate mRNA levels for FAS, ACC, and glycerol-3-P dehydrogenase (GPDH). Treatment with insulin and various concentrations of d-glucose increased mRNA levels for FAS (280%), ACC (93%), and GPDH (633%) in a dose-dependent manner (ED50 8-16 mm). Mannose similarly elevated mRNA levels, but galactose and fructose were only partially effective. l-glucose had no effect. Omission of glutamine from the culture medium markedly diminished the stimulatory effect of glucose on mRNA expression. Since glutamine is a crucial amide donor in hexosamine biosynthesis, we interpret these data to mean that glucose flux through the HBP is linked to regulation of lipogenesis through control of gene expression. Further evidence for hexosamine regulation was obtained using glucosamine, which is readily transported into adipocytes where it directly enters the HBP. Glucosamine was 15-30 times more potent than glucose in elevating FAS, ACC, and GPDH mRNA levels (ED50 approximately 0.5 mm). In summary: 1) GPDH, FAS, and ACC mRNA levels are upregulated by glucose; 2) glucose-induced up-regulation requires glutamine; and 3) mRNA levels for lipogenic enzymes are up-regulated by glucosamine. Hyperglycemia is the hallmark of diabetes mellitus and leads to insulin resistance, impaired glucose metabolism, and dyslipidemia. We postulate that disease pathophysiology may have a common underlying factor, excessive glucose flux through the HBP.
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PMID:Role of hexosamine biosynthesis in glucose-mediated up-regulation of lipogenic enzyme mRNA levels: effects of glucose, glutamine, and glucosamine on glycerophosphate dehydrogenase, fatty acid synthase, and acetyl-CoA carboxylase mRNA levels. 1275 50


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