Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These results demonstrate that two well-studied metalloenzymes, carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) and pyruvate:ferredoxin oxidoreductase (PFOR), can reduce protons to H2 and, at much lower rates, oxidize H2 to protons and electrons. To our knowledge, this if the first time that PFOR has been shown to have hydrogenase activity. CODH/ACS and PFOR evolved H2 at maximum rates when CO and pyruvate were the electron donors, respectively, and when electron acceptors are absent; dithionite was a very poor substitute. PFOR, when purified to greater than 99% homogeneity, exhibited a specific activity for pyruvate-dependent H2 production of 135 nmol min-1 mg-1. The H2 evolution activity divided by the H2 uptake activity was 282:1; the highest ratio previously reported (22:1) was with the membrane-bound hydrogenase from Rhodospirillum rubrum [Fox, J.D., Kerby, R. L., Roberts, G. P., & Ludden, P. W. (1996) J. Bacteriol. 178, 1515-1524]. Highly purified samples of CODH/ACS (> 99% homogeneity) exhibited a specific activity of CO-dependent H2 evolution in the absence of electron carrier of 590 nmol min-1 mg-1. Equivalent rates of CO oxidation and H2 production were observed when determined in the absence of electron acceptor. This level of activity can account for the rate of H2 production that has been observed by growing cultures of Clostridium thermoaceticum and could solve the paradox that the highly CO-sensitive hydrogenases from acetogenic bacteria evolve H2 when grown on CO. The ratio of the rates of (H2 evolution):(H2 uptake) for purified CODH/ACS is between 20:1 and 30:1. H2 evolution and uptake by CODH/ACS were strongly inhibited by cyanide (ki = 1 microM), indicating that these reactions are catalyzed by cluster C, the site of CO oxidation. Our results extend earlier findings that the CODHs from Methanosarcina barkeri [Bhatnagar, L., Krzycki, J. A., & Zeikus, J. G. (1987) FEMS Microbiol. Lett. 41, 337-343] and Oligotropha carboxydovorans [Santiago, B., & Meyer, O. (1996) FEMS Microbiol. Lett. 136, 157-162] exhibit hydrogenase activity. Mechanistic implications of hydrogenase activity are discussed. Several physiological roles for proton reduction by CODH/ACS and PFOR are discussed, including the prevention of radical formation from reduced metal clusters when electron carriers (ferredoxin, flavodoxin, etc.) are limiting.
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PMID:Unleashing hydrogenase activity in carbon monoxide dehydrogenase/acetyl-CoA synthase and pyruvate:ferredoxin oxidoreductase. 896 45

Normal physiological responses to carbohydrate shortages cause the liver to increase the production of ketone bodies from the acetyl-CoA generated from fatty acid oxidation. This allows the use of ketone bodies for energy, thereby preserving the limited glucose for use by the brain. This adaptative response is switched off by insulin rapidly inhibiting the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) gene, which is a key control site of ketogenesis. We decided to investigate the molecular mechanism of this inhibition. In the present study, we show that FKHRL1, a member of the forkhead in rhabdosarcoma (FKHR) subclass of the Fox family of transcription factors, stimulates transcription from transfected 3-hydroxy-3-methylglutaryl-CoA synthase promoter-luciferase reporter constructs, and that this stimulation is repressed by insulin. An FKHRL1-responsive sequence AAAAATA, located 211 bp upstream of the HMGCS2 gene transcription start site, was identified by deletion analysis. It binds FKHRL1 in vivo and in vitro and confers FKHRL1 responsiveness on homologous and heterologous promoters. If it is mutated, it partially blocks the effect of insulin in HepG2 cells, both in the absence and presence of overexpressed FKHRL1. These results suggest that FKHRL1 contributes to the regulation of HMGCS2 gene expression by insulin.
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PMID:Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1. 1202 2