Cytochrome P450 2: peroxidative reactions of diversozymes.
Cytochrome P450, the most versatile biological catalyst known, was originally named as a pigment having a carbon monoxide difference spectrum at about 450 nm and no known function. Recent progress in many laboratories has revealed that the P450 superfamily has immense diversity in its functions, with hundreds of isoforms in many species catalyzing many types of chemical reactions. We believe it is safe to predict that each mammalian species may be found to have up to a hundred P450 isoforms that respond in toto to a thousand or more inducers and that, along with P450s from other sources, metabolize a million or more potential substrates. Accordingly, the name DIVERSOZYMES is proposed for this remarkable family of hemoproteins. This paper reviews the peroxidative reactions of Diversozymes, including peroxides as oxygen donors in hydroxylation reactions, as substrates for reductive beta-scission, and as peroxyhemiacetal intermediates in the cleavage of aldehydes to formate and alkenes. Lipid hydroperoxides undergo reductive beta-cleavage to give hydrocarbons and aldehydic acids. One of these products, trans-4-hydroxynonenal, inactivates P450, particularly alcohol-inducible 2E1, in what may be a negative regulatory process. Although a P450 iron-oxene species is believed to be the oxygen donor in most hydroxylation reactions, an iron-peroxy species is apparently involved in the deformylation of many aldehydes with desaturation of the remaining structure, as in aromatization reactions.
Coon
M J
MJ
Department of Biological Chemistry, The University of Michigan, Ann Arbor 48109-0606, USA.
Vaz
A D
AD
Bestervelt
L L
LL
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006801:Humans; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism*
D000447:Aldehydes; D008054:Lipid Peroxides; D010545:Peroxides; D003577:Cytochrome P-450 Enzyme System; C027576:4-hydroxy-2-nonenal