Oxidation of clozapine and ascorbate by myeloperoxidase.
The kinetics and spectra of the reactions of clozapine with compounds I and II of myeloperoxidase were investigated using both single- and sequential-mixing stopped-flow techniques, steady-state kinetics, and spectrophotometric measurements. The results show conclusively that both compounds I and II are reduced in one-electron reactions with clozapine. At pH 7.0 the rate constant for compound I reacting with clozapine is (1.5 +/- 0.1) x 10(6) M(-1) s(-1) and for compound II (4.8 +/- 0.1) x 10(4) M(-1) s(-1). The physiological pH of 7.4 was found to be optimal for the oxidation of clozapine by compound I. The rate constant for compound I reacting with ascorbate is (1.1 +/- 0.1) x 10(6) M(-1) s(-1) and for compound II (1.1 +/- 0.2) x 10(4) M(-1) s(-1), both obtained at pH 7.0. Experiments with both clozapine and ascorbate present showed that ascorbate acts both as a competitive inhibitor and free radical scavenger.
Hsuanyu
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Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.
Dunford
H B
HB
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D002417:Cattle; D003024:Clozapine / Q000378:metabolism*; D007700:Kinetics; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*
D009195:Peroxidase; D003024:Clozapine; D001205:Ascorbic Acid