Electron-transport cytochrome P-450 system is involved in the microsomal metabolism of the carcinogen chromate
作者： J.D. Garcia , K.Wetterhahn Jennette
DOI: 10.1016/S0162-0134(00)80286-X
关键词: Biochemistry 、 Chemistry 、 Enzyme kinetics 、 Reductase 、 Cytochrome 、 Cofactor 、 Microsome 、 Dissociation constant 、 Metabolism 、 Chromate conversion coating 、 Inorganic chemistry
摘要: Abstract The kinetics of chromate reduction by liver microsomes isolated from rats pretreated with phenobarbital or 3-methylcholanthrene NADPH NADH cofactor have been followed. Induction cytochrome P-450 and NADPH-cytochrome reductase activity in pretreatment caused a decrease the apparent chromate-enzyme dissociation constant, Km, an increase second-order rate kcat/Km, but did not affect kcat NADPH-mediated microsomal metabolism chromate. P-448 3-methycholanthrene microsomes. NADH-mediated were unaffected drug treatments. effects specific enzyme inhibitors on determined. 2′-AMP 3-pyridinealdehyde-NAD, NADH-cytochrome b5 reductase, inhibited NADH. Metyrapone carbon monoxide, P-450, chromate, whereas high concentrations dimethyl-sulfoxide (0.5 M) enhanced rate. These results suggest that electron-transport system is involved systems. cofactors supply reducing equivalents ultimately to which functions as metabolism. lower oxidation state(s) produced upon may represent ultimate carcinogenic form(s) chromium. studies provide evidence for role activation inorganic carcinogens.
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