CYTOCHROME-P450 .2. PEROXIDATIVE REACTIONS OF DIVERSOZYMES

Cytochrome P450, the most versatile biological catalyst known, was ori ginally named as a pigment having a carbon monoxide difference spectru m at about 450 nm and no known function, Recent progress in many labor atories has revealed that the P450 superfamily has immense diversity i n its functions, with hundreds of isoforms in many species catalyzing many types of chemical reactions, We believe it is safe to predict tha t each mammalian species may be found to have up to a hundred P450 iso forms that respond in tote to a thousand or more inducers and that, al ong with P450s from other sources, metabolize a million or more potent ial substrates, Accordingly, the name DIVERSOZYMES is proposed for thi s remarkable family of hemoproteins. This paper reviews the peroxidati ve reactions of Diversozymes, including peroxides as oxygen donors in hydroxylation reactions, as substrates for reductive beta-scission, an d as peroxyhemiacetal intermediates in the cleavage of aldehydes to fo rmate and alkenes, Lipid hydroperoxides undergo reductive beta-cleavag e to give hydrocarbons and aldehydic acids. One of these products, tra ns-4-hydroxynonenal, inactivates P450, particularly alcohol-inducible 2E1, in what may be a negative regulatory process, Although a P450 iro n-oxene species is believed to be the oxygen donor in most hydroxylati on reactions, an iron-peroxy species is apparently involved in the def ormylation of many aldehydes with desaturation of the remaining struct ure, as in aromatization reactions.