Peroxidases: a role in the metabolism and side effects of drugs.
Current safety screening of drug candidates or new chemical entities for reactive metabolite formation focuses on the role of cytochrome P450. However, peroxidases also have a major role in drug metabolism, and peroxidase-catalyzed drug oxidation could lead to reactive metabolite formation, resulting in oxidative stress and cytotoxicity. Here, the different classes of human peroxidases are summarized and the molecular mechanisms of peroxidase-catalyzed drug metabolism are discussed. In addition, evidence is presented that indicates a role of these enzymes in drug toxicity.
Tafazoli
Shahrzad
S
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada, M5S 2S2.
O'Brien
Peter J
PJ
D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010544:Peroxidases / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases