HUMAN CYTOCHROME-P-450 ENZYMES

Cytochrome P-450 (P-450) enzymes have been studied extensively in experimental animal models and much is known regarding their structures, regulation, and mechanisms of catalysis. In recent years investigations have been extended to the human P-450s. There are more than 30 different characterized human P-450s in the superfamily, and collectively they are probably the most significant enzymes involved in the metabolism of drugs, carcinogens, and steroids. The levels of many of the P-450s and their catalytic activities can vary considerably because of polymorphism, induction, and inhibition. The catalytic specificity of the P-450s can range from being very non-discriminatory to very exacting, and clinical consequences of drugs and steroids can be related to variations in P-450 levels. Defects in the rate-limiting P-450 reactions in steroidogenesis (due to genetic deficiencies) have been shown to be debilitating and even fatal.