On the possible relationship of cytochrome P-450 to alcohol metabolism: fundamental aspects of the microsomal hydroxylation system, including properties and interactions of the components.

Abstract

Recent studies on the cytochrome P-450-containing enzyme system of liver microsomes have shown that the cytochrome is present as a number of distinct isozymes, one of which is induced in vivo by the administration of aromatic hydrocarbons, as well as several forms which are less well characterized and not known to be inducible. The various cytochromes exhibit partially selective but overlapping activities with a variety of substrates. Additional components are NADPH-cytochrome P-450 reductase, which binds to the cytochrome to form a tight 1:1 complex, phosphatidylcholine, and cytochrome b5, the role of which is still not clear. Recent evidence indicates that some of the components are mutually beneficial in favoring formation of a functional complex. For example, phosphatidylcholine enhances the binding of substrate and reductase to P-450LM2, reductase enhances the binding of phosphatidylcholine, and substrate (benzphetamine) facilitates the binding of reductase. The possible effect of ethanol on these interactions should be considered in evaluating the reported inhibition by high concentrations of ethanol of reactions catalyzed by liver microsomal cytochrome P-450.