霊長類のシトクロムP-450をめぐる話題

概要

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We have mainly performed enzymological comparative study for cytochrome P-450 (P-450) in primate liver microsomes. In this review, we describe recent interesting topics for primate P-450. Comparative study for non-human primate P-450 of liver microsomes started by our report of purification of carb-eating monkey liver P-450. The purified P-450 had relatively lower catalytic activities for exogenous compounds. The cytochrome could hydroxylate testosterone, endogenous substrate, at 6β position. Studies for human liver P-450 were performed from the early years by numerous numbers of investigators. First study of purification of human liver P-450 was reported at 1979. At present, nearly 10 species of P-450 were purified and their functions and structures were revealed. We have purified fetal P-450 (P-450HFLa) and provided its physiological function. P-450HFLa is the 16α-hydroxylase of dehydroepiandoro-sterone 3-sulfate. Recently, it was reported that one of the reason of individual differences in human liver drug metabolism was due to lack of specific form of P-450 isozymes (genetic polymorphism). In the future, we would like to further clarify the functions of human and nonhuman primates P-450 isozymes and to establish the correspondence between many rodents and primates P-450s and analyze P-450 isozyme pattern of human liver and utilize for selection of drug and determination of dosage in clinical pharmacology.
日本医療薬学会の論文
1989-03-20