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Molecular aspects of drug metabolism.

: Drug oxidation is linked to a liver-microsomal electron transport system consisting of at least two components - cytochrome P-450 and the NADPH-cytochrome P-450 reductase. Cytochrome P-450 is also involved in the hydroxylation of lipid-soluble endogenous compounds, such as steroid hormones and fatty acids. Substrates capable of undergoing hydroxylation bind to cytochrome P-450 and the reduction of the cytochrome P-450-substrate complex so formed may well be the rate-limiting step in the over-all hydroxylation process. It is suggested that the competitive inhibition that various substrates exert on each other's hydroxylation is due to a competition for binding to a common cytochrome P-450 species in the liver microsomes.