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Biomimetic models for monooxygenases
Author(s) -
Zbaida Shmuel,
Kariv Rami
Publication year - 1989
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510100502
Subject(s) - chemistry , hydroxylation , cytochrome , monooxygenase , cytochrome p450 , oxidative phosphorylation , hydrogen peroxide , microsome , hemeprotein , reductase , demethylation , substrate (aquarium) , porphyrin , stereochemistry , biochemistry , heme , enzyme , biology , gene expression , dna methylation , gene , ecology
The microsomal mixed function oxidase system contains the cytochrome P‐450 oxidative drug metabolizing family of enzymes. The catalytic cycle of cytochrome P‐450 is believed to involve the formation of an active iron‐oxygen species which is responsible for oxygen transfer to the substrate. This assumption is supported by the fact that a number of peroxidative agents can replace NADPH, the reductase, and oxygen as co‐reactants in most oxidative reactions of microsomal cytochrome P‐450. We have found that a mixture of either ferrous or ferric ions with hydrogen peroxide (Fenton and Ruff reagents) can serve as biomimetic models for cytochrome P‐450 in hydroxylation, exposidation, sulfoxidation, and N‐demethylation of various drugs. The existance of an iron‐oxo active species in both Fenton and Ruff type reactions has been postulated and provides reaction cycles similar to those of cytochrome p‐450. Other model systems for the hepatic hydroxylation and epoxidation using transition metal complexes with porphyrin are also discussed. The present paper reviews the various biomimetic models of the heme cytochrome P‐450 and emphasizes their simulation of hepatic drug metabolism and their potential medical and industrial applications.