OXIDATIVE DRUG METABOLISM IN HUMAN LIVER MICROSOMES

¹ Departments of Biochemistry and Anesthesiology, The University of Texas Southwestern Medical School, Dallas, Texas

Isolated human liver microsomes were studied with respect to reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase, NADPH-cytochrome P-450 reductase, aminopynine demethylase activity and the content of cytochrome P-450. Aminopyrine demethylation correlated well with the level of NADPH-cytochrome P-450 reductase activity and NADPH-cytochrome c reductase activity, but not with the content of cytochrome P-450. The mean values for cytochrome P-450 content and levels of both reductases were lower than those reported for laboratory animals. Antibodies prepared in rabbits to porcine liver NADPH-cytochrome c reductase concomitantly inhibited human NADPH-cytochrome c reductase, NADPH-cytochrome P-450 reductase and aminopyrine demethylation. Common precipitin lines were observed on Ouchterlony double diffusion plates between human and porcine liver microsomes. Thus, the flavoprotein involved in human liver microsomal drug metabolism is immunochemically and functionally similar to that of another mammalian species.

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