NADPH-cytochrome c reductase and its role in microsomal cytochrome P-450-dependent reactions.

The study of liver microsomal electron transport and drug metabolism activities involving NADPH-cytochrome c reductase has been performed using immunochem ical techniq ues ( I -4). This approach has been particularly valuable in establishing the role of this flavoprotein in the reduction of microsomal cytochrome P-450 and, thus, in the metabolism of drugs (2, 3). The existence of NADPH-cytochrome c reductase activity in a variety of tissues including kidney, spleen, adrenal cortex, heart, and lung has led to a closer examination of the role of this enzymic activity in cytochrome P-450-mediated reactions in these tissues. It has been demonstrated by Masters and Ziegler (5) that the two NADPH-dependent electron transport systems in porcine liver microsomes contain separate and distinct flavoproteins (fig. I): NADPH-cytochrome c reductase and NADPH-dependent mixed function amine oxidase (N-oxidase). This conclusion was based on the differential purification of the two enzymic activities, the induction of the re-