Metabolic Reactions: Types of Reactions of Cytochrome P450 Enzymes

Abstract

Collectively the cytochrome P450 enzymes (EC 1.14.14.1, unspecific monooxygenase) catalyze thousands of different reactions. Even when allowance is made for the similarity of different substrates the number of reactions is still considerable (Fig. 1). However, these can be considered in terms of a few groups of oxidative reactions that proceed through similar chemistry. Most of the oxidative reactions have been demonstrated with biomimetic chemical models, and it is thought that the protein structure determines the catalytic specificity through complementarity to the transition state. The possibility that specific amino acid residues participate directly in chemical events (e.g., specific acid-base catalysis) has not been considered in depth - indeed, even the function of the axial thiolate ligand is not precisely known (Dawson 1988; Imai et al. 1989). The biomimetic model oxidations are not dependent upon the presence of a particular metal, ligand structure, or solvent. Indeed, much has been inferred about the catalytic mechanism of the enzyme from studies with these models (Mansuy et al. 1989) because some of the postulated enzyme intermediates are probably inaccessible for direct observation.