doi:10.1006/bbrc.1999.0569">
 

Title

Cumene hydroperoxide-supported demethylation reactions catalyzed by cytochrome P450 2B4 lacking the NH2-terminal sequence

Document Type

Article

Publication Date

1999

Department/School

Chemistry

Abstract

Catalytic activities of cytochrome P450 2B4 lacking NH2-terminal amino acids 2-27 (wt Delta 2B4) and that of truncated 2B4 containing a Pro to Ser mutation at position 221 were examined in a system supported by cumene hydroperoxide. Demethylation activities of either truncated 2B4 with N-methylaniline, N,N-dimethylaniline, and d-benzphetamine were lower than those of Liver microsomal 2B4, whereas the rate of 1-phenylethanol oxidation to acetophenone catalyzed by liver microsomal and truncated 2B4 enzymes was nearly the same. The K-m and V-max values for cumene hydroperoxide in the demethylation of N-methylaniline by wt Delta 2B4 were 20% and 28%, respectively, of those obtained for 2B4. The reaction with wt Delta 2B4 displayed a lesser dependence on phospholipid than did that with 2B4, and a complex relationship between activity and substrate concentration. The results suggest that the NH2-terminal region contributes to interaction of oxidant, substrate, and phospholipid in cumene hydroperoxide-supported reactions catalyzed by cytochrome P450 2B4. (C) 1999 Academic Press.

Link to Published Version

doi:10.1006/bbrc.1999.0569

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