Non-specific inhibition of human cytochrome P450-catalyzed reactions by hemin.

Hemin, a stable form of heme, is known to have an antimutagenic effect. Inhibitory effects of hemin on the cytochrome P450 (CYP)-catalyzed reactions of human liver microsomes and reconstituted systems containing purified CYP and NADPH-cytochrome P450 reductase (NPR) were seen. Hemin non-specifically inhibited all of the microsomal CYP activities examined. Hemin also inhibited 7-ethoxyresorufin O-deethylation, 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin O-demethylation, and testosterone 6beta-hydroxylation catalyzed by purified CYPs 1A2, 2D6, and 3A4, with IC50 values of 27, 19, and 2.4 microM, respectively. Hemin also inhibited reduction of cytochrome c and ferricyanide by NPR, as much as 47%. Spectrally detectable CYP was destroyed in human liver microsomes and in a reconstituted system in the presence of hemin and an NADPH-generating system. We propose that the antimutagenic effect of hemin might be due to inhibition of CYP and NPR enzymes involved in the bioactivation of mutagens.