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)

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)
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PMID:Effects of lovastatin on hepatic fatty acid metabolism. 790 61

Human apocrine and sebaceous glands function to secrete lipids, predominantly triglycerides, fatty acids, cholesterol and its esters, and, in the sebaceous gland, squalene. The enzymes that catalyze the important regulatory steps in cholesterol and fatty acid biosyntheses, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and acetyl-CoA carboxylase, respectively, were therefore studied in isolated human skin appendages, and their relevant kinetic parameters determined. The enzyme activities that were observed can account for previously described rates of incorporation of radiolabeled substrates into the appropriate lipids by glands in vitro. Reduced enzyme activities following homogenization in the presence of fluoride indicated that both of these enzymes in skin appendages are inactivated by phosphorylation. The activity of the enzyme known to catalyze this phosphorylation, the AMP-activated protein kinase, was also measured. Compactin was shown to inhibit HMG-CoA reductase in homogenates of these appendages. Conversely, incubation of whole sebaceous glands with compactin resulted in the stimulation of enzyme activity, which suggests that these appendages can respond to diminishing cholesterol levels. The effect of exogenous low density lipoprotein and 25-hydroxycholesterol on HMG-CoA reductase activity from skin appendages was investigated. HMG-CoA reductase activity in both apocrine and sebaceous glands was reduced following incubation with either low density lipoprotein or 25-hydroxycholesterol. Low density lipoprotein receptor and lipoprotein lipase mRNA expression was also detected in skin appendages. These results indicate that apocrine and sebaceous glands have the capacity to sequester dietary cholesterol and fatty acids that may have important implications for the understanding of both acne and axillary odor.
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PMID:The activity of HMG-CoA reductase and acetyl-CoA carboxylase in human apocrine sweat glands, sebaceous glands, and hair follicles is regulated by phosphorylation and by exogenous cholesterol. 966 1

We combine the use of labeled precursors with enzyme inhibitors to decipher the biosynthetic pathway of pheromone biosynthesis and the rate-limiting step/s that are regulated by pheromone biosynthesis activating neuropeptide (PBAN). We demonstrate that Plodia interpunctella is able to utilize hexadecanoic acid, and to a lesser extent tetradecanoic acid, for the biosynthesis of the main pheromone component (Z,E)-9,12-tetradecadienyl acetate. This indicated that the main pathway involves a Delta11 desaturase, chain shortening, followed by a Delta12 desaturase, but that a functional Delta9 desaturase could also be utilized. Using reverse transcription-quantitative real-time polymerase chain reaction (RT-QPCR) we distinguish two out of nine possible desaturase gene transcripts in P. interpunctella that are expressed at the highest levels. The rate-limiting step for PBAN-stimulation was studied in two moth species so as to compare the biosynthesis of a diene (P. interpunctella) and a monoene (Helicoverpa armigera) main pheromone component. In both species, incorporation of label from the (13)C sodium acetate precursor was activated by PBAN whereas no stimulatory action was observed in the incorporation of the precursors: (13)C malonyl coenzyme A; hexadecanoic 16,16,16-(2)H(3) or tetradecanoic 14,14,14-(2)H(3) acids. The acetyl coenzyme A carboxylase (ACCase) inhibitor, Tralkoxydim, inhibited the PBAN-stimulation of incorporation of stable isotope whereas the fatty-acyl reductase inhibitor, Mevastatin, failed to influence the stimulatory action of PBAN. These results provide irrefutable support to the hypothesis that PBAN affects the production of malonyl coenzyme A from acetate by the action of ACCase in the pheromone glands of these moths.
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PMID:Pheromone biosynthetic pathways: PBAN-regulated rate-limiting steps and differential expression of desaturase genes in moth species. 1840 33