Enzymatic reduction of chromium(VI) by human hepatic microsomes.
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.
Pratt
P F
PF
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Myers
C R
CR
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
D002274:Carcinogens, Environmental; D002857:Chromium; C074702:chromium hexavalent ion; D009249:NADP; D002248:Carbon Monoxide; D013793:Thallium; D005954:Glucosephosphate Dehydrogenase; D010100:Oxygen; D008797:Metyrapone