title: Enzymatic reduction of chromium(VI) by human hepatic microsomes.
abstract: The reduction of chromium(VI) by human hepatic microsomes was investigated. The reduction rates were proportional to the amount of microsomes added and reduction was mediated by an NADPH-dependent enzymatic system which exhibited a Km for chromate of 1.04 +/- 0.18 microM and a Vmax of 5.03 +/- 0.49 nmol/min/mg protein. Relative to incubation under 0% O2, 21% O2 inhibited microsomal Cr(VI) reduction in three individuals by 53, 36 and 37%. Cr(VI) reduction was not inhibited by metyrapone, carbon monoxide, aminopyrine, piperonyl butoxide or chloroform, suggesting that cytochrome P450s did not play a major role. Thallium trichloride (0.13 and 0.26 mM), a known flavoprotein inhibitor, caused a complete inhibition of both Cr(VI) reduction and NADPH:cytochrome P450 (c) reductase activity. A partial inhibition of Cr(VI) reduction was seen in the presence of n-octylamine, which may suggest a possible role for flavin-containing monooxygenase (FMO). Overall, human microsomal Cr(VI) reduction is very different from the P450-mediated microsomal reduction observed in rodents. Specifically, the human system is much less oxygen-sensitive, has a much greater affinity for chromate and is apparently mediated by flavoproteins.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
authors.forename: P F
authors.initials: PF
authors.lastname: Pratt
authors.forename: C R
authors.initials: CR
authors.lastname: Myers
mesh_terms: D000328:Adult; D002248:Carbon Monoxide / Q000494:pharmacology; D002274:Carcinogens, Environmental / Q000378:metabolism*; D002857:Chromium / Q000378:metabolism*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D013793:Thallium / Q000494:pharmacology
chemical_list: D002274:Carcinogens, Environmental; D002857:Chromium; C074702:chromium hexavalent ion; D009249:NADP; D002248:Carbon Monoxide; D013793:Thallium; D005954:Glucosephosphate Dehydrogenase; D010100:Oxygen; D008797:Metyrapone