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)

Addition of triiodothyronine (T3) to chick-embryo hepatocytes in culture causes increased accumulations of malic enzyme, fatty acid synthase, acetyl-CoA carboxylase and their mRNAs. H-8 and other protein kinase inhibitors inhibited the T3-induced accumulations of these lipogenic enzymes and their mRNAs but had no effect on the activities of 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase, enzymes not induced by T3 in chick-embryo hepatocytes. H-8 also had no effect on the activities of malic enzyme, fatty acid synthase, and acetyl-CoA carboxylase in hepatocytes not treated with T3. Synthesis of soluble protein, levels of mRNAs for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, and induction of metallothionein mRNA by Zn2+ were unaffected by H-8 at concentrations that inhibited the T3-induced accumulation of lipogenic enzymes and their mRNAs. H-8 inhibited T3-induced transcription of the genes for both malic enzyme and fatty acid synthase but had little effect on transcription of the beta-actin or glyceraldehyde-3-phosphate dehydrogenase genes or on total RNA synthesis in isolated nuclei. H-8 also had no effect on binding of T3 to its nuclear receptor. In isolated nuclei, H-8 inhibited phosphorylation of total protein by 15-20%. Phosphorylation of only one major protein was consistently and substantially inhibited, indicating that the effect of H-8 was selective. These results suggest that on-going protein phosphorylation is required specifically for stimulation of transcription of the lipogenic genes by T3.
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PMID:Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl-coenzyme A carboxylase, and their mRNAs are blocked by protein kinase inhibitors. Transcription is the affected step. 168 Jan 29

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.
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PMID:Inhibition of fatty acid synthesis by expression of an acetyl-CoA carboxylase-specific ribozyme gene. 793 24

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.
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PMID:Lipogenic enzyme and apoprotein messenger RNAs in long-term primary culture of chicken hepatocytes. 810 Feb 36

The current model of the nutrient sensing mechanism in pancreatic beta-cells implies that malonyl-CoA plays a key role. According to this hypothesis, glucose activation of acetyl-CoA carboxylase triggers a rapid production of malonyl-CoA which inhibits carnitine palmitoyltransferase 1 and the importation of fatty acyl-CoA into the mitochondria for oxidation. The increase in cytosolic long chain fatty acyl-CoA leads to the exocytosis of insulin by a mechanism which has not yet been clearly defined. To obtain direct evidence that ACC plays a central role in this process, we generated stable transfectants of an insulin secreting cell line (INS-1) that express ACC specific antisense mRNA. The amounts of ACC mRNA and the protein level were specifically decreased in these stable clones compared to those of the control cells. The glucose activation of ACC in these cells was also significantly diminished. Both acute and long-term induction of insulin secretion by glucose were decreased. This decrease was inversely correlated to the levels of ACC activity in clones. In these clones, the insulin secretion induced by other nutrients, amino acids and ketocaproate, is also impaired, while the KCl-induced insulin secretion remains unchanged. Decreased ACC expression was accompanied by impaired malonyl-CoA production and elevated fatty acid oxidation. The expressions of the pancreatic specific glucokinase, glucose transporter 2 or beta-actin in these cells, as well as glucose utilisation were not affected, suggesting that the effect of the expression of the ACC mRNA specific gene on insulin secretion is specifically related to the decrease in the amount of ACC gene products. These results provide direct evidence of a causal relationship between ACC and insulin secretion.
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PMID:Essential role of acetyl-CoA carboxylase in the glucose-induced insulin secretion in a pancreatic beta-cell line. 950 15

Twenty-eight Angus steers (289 kg) were finished on a high-concentrate diet (85% concentrate: 15% roughage; CONC), or endophyte-free tall fescue pastures with corn grain supplement (0.52% of BW; PC), corn oil plus soybean hull supplement (0.10% of BW corn oil plus 0.45% of BW soybean hulls; PO), or no supplement (pasture only; PA). Subcutaneous adipose tissues were processed for total cellular RNA extraction and fatty acid composition by GLC. Relative expression of genes involved in lipogenesis [fatty acid synthase (FASN), acetyl-CoA carboxylase, lipoprotein lipase, stearoyl-CoA desaturase (SCD)] and activators of transcription [(peroxisome proliferator-activated receptor-gamma), C/EBPalpha, sterol regulatory binding protein-1, signal transducer and activator of transcription-5, and Spot-14] was determined by real-time quantitative PCR. Housekeeping gene (glyceraldehyde 3-phosphate dehydrogenase and beta-actin) expression was used in analysis to normalize expression data. Total fatty acid content was greatest (P < 0.001) for CONC and least (P < 0.001) for PA. Supplementation of grazing cattle increased (P < 0.001) total fatty acid content compared with PA, but concentrations were less (P < 0.001) than for CONC. Myristic and palmitic acid contents were greater (P < 0.001) for CONC than for PO and PC, which were greater (P < 0.001) than for PA. Stearic acid content was greater (P < 0.01) for PO than for CONC, PC, and PA. Finishing on CONC increased (P < 0.001) total MUFA content by 68% compared with PA. Corn grain supplementation increased (P < 0.001) MUFA content compared with PA; in contrast, MUFA content did not differ (P > 0.05) between PO and PA. Corn oil supplementation increased (P < 0.001) trans-11 vaccenic acid content in subcutaneous fat by 1.2-, 1.7- and 5.6-fold relative to PA, PC, and CONC, respectively. Concentrations of the cis-9, trans-11 CLA isomer were 54, 58, and 208% greater (P < 0.01) for PO than for PA, PC, and CONC, respectively. Corn grain supplementation to grazing steers did not alter (P > 0.05) the cis-9, trans-11 CLA isomer compared with PA. Oil supplementation increased (P < 0.001) linoleic acid (C18:2) content by 56, 98 and 262% compared with CONC, PC, and PA, respectively. Relative mRNA expression of SCD was upregulated (P < 0.001) by 46-, 18- and 7-fold, respectively, for CONC, PC, and PO compared with PA. Relative FASN mRNA expression was also upregulated (P = 0.004) by 9- and 5-fold, respectively, for CONC and PC compared with PA. Grain feeding, either on CONC or supplemented on pasture, upregulated FASN and SCD mRNA to increase MUFA and de novo fatty acids in subcutaneous adipose tissue. Upregulation of SCD with grain feeding and reduced tissue CLA concentrations suggest that the decreased CLA concentrations were the result of limited substrate (trans-11 vaccenic acid) availability.
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PMID:Corn oil or corn grain supplementation to steers grazing endophyte-free tall fescue. II. Effects on subcutaneous fatty acid content and lipogenic gene expression. 1902 50