Biodiversity of the P450 catalytic cycle: yeast cytochrome b(5)/NADH cytochrome b(5) reductase complex efficiently drives the entire sterol 14-demethylation (CYP51) reaction

The widely accepted catalytic cycle of cytochromes P450 (CYP) involves the electron transfer from NADPH cytochrome P450 reductase (CPR), with a potent ial for second electron donation from the microsomal cytochrome b(5)/NADH c ytochrome 65 reductase system. The latter system only supported CYP reactio ns inefficiently. Using purified proteins including Candida albicans CYP51 and yeast NADPH cytochrome P450 reductase, cytochrome bs and NADH cytochrom e 65 reductase, we show here that fungal CYP51 mediated sterol 14 alpha-dem ethylation can be wholly and efficiently supported by the cytochrome b(5)/N ADH cytochrome 65 reductase electron transport system. This alternative cat alytic cycle, where both the first and second electrons were donated via th e NADH cytochrome 65 electron transport system, can account for the continu ed ergosterol production seen in yeast strains containing a disruption of t he gene encoding CPR, (C) 1999 Federation of European Biochemical Societies .