LAURATE HYDROXYLATION AND DRUG METABOLISM IN PIG LIVER AND KIDNEY MICROSOMES AND IN RECONSTITUTED SYSTEMS FROM PIG LIVER AND KIDNEY

Abstract

This chapter discusses laurate hydroxylation and drug metabolism in pig liver and kidney microsomes, and in reconstituted systems from pig liver and kidney. The study of monooxygenase systems in hepatic and extrahepatic tissues has necessitated the use of a variety of substrates to obtain measurable rates of metabolism. This situation suggests that there may be cytochromes P-450 in various organs with differing substrate specificities and physico-chemical properties. The metabolism of lauric acid to ω- and (ω-l)-hydroxylated products was described in rat liver microsomes and it was later shown to proceed at similar specific activities in rat kidney microsomes. Cytochrome P-450 was implicated as the terminal oxygenase in these systems. The physiological significance of fatty acid hydroxylation in liver is a subject of controversy, but the fact remains that it is an active substrate for liver and kidney microsomal metabolism. The chapter presents the studies in which lauric acid has been used in addition to other substrates to differentiate between two cytochromes P-450 Antibodies prepared to these cytochromes P-450 further substantiate their immunochemical non-identity and substrate specificity.