STUDIES ON LIVER AND KIDNEY DRUG AND LAURIC ACID MONOOXYGENASES IN BOTH MICROSOMAL AND RECONSTITUTED SYSTEMS

Abstract

This chapter presents the studies on liver and kidney drug, and lauric acid monooxygenases in microsomal and reconstituted systems. The liver microsomal monooxygenase system metabolizes a broad spectrum of substrates, including xenobiotics, steroids, and fatty acids. However, the kidney microsomal monooxygenase system, while containing the same components as the liver system, metabolizes fatty acids at a higher specific activity than any other known substrate. The chapter describes a comparative study of the reductases and cytochromes P-450 of pig liver and kidney microsomes that was carried out to elucidate the differences in substrate specificity between the two organs. In this study, the purified kidney cytochrome P-450 from untreated pigs was found to be immunochemically distinct from the purified liver cytochrome P-450 from phenobarbital (PB)–induced pigs. In addition, differences between these purified cytochromes P-450 were found in benzphetamine demethylation and laurate hydroxylation activities measured in reconstituted systems. The two cytochromes P-450 that were isolated from liver microsomes of PB-induced pigs and from kidney microsomes of untreated pigs show no immunochemical cross-reactivity. They exhibit distinct substrate specificities that are affected neither by lipid milieu nor by the source of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH)–cytochrome P-450 reductase.