Stereochemistry of Cytochrome P-450 Reactions

Abstract

Generally, most enzymes have a high degree of substrate specificity. In contrast, one of the primary characteristics of the cytochrome P-450s is a lack of substrate specificity. Specific isozymes will not only oxidize a number of different substrates but will often transform a single substrate into a number of different products. Indeed, it appears that almost any organic molecule that can reach the active site of the enzyme will be oxidized. This high degree of chemical reactivity demands that there must be some structural feature that controls access to the active site in order to prevent excess turnover of endogenous substances critical to the normal functioning of the organism. The structural feature that serves this role is the lipoidal character of the enzyme complex which results from the fact that it is membrane bound. Thus, the known endogenous substrates for the cytochrome P-450s, the steroids, prostaglandins, and fat-soluble vitamins, are all highly lipophilic substances.