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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
Author(s) -
Lamb David C.,
Kelly Diane E.,
Manning Nigel J.,
Kaderbhai Mustak A.,
Kelly Steven L.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01548-3
Subject(s) - cytochrome b5 , cytochrome p450 reductase , cytochrome c1 , reductase , coenzyme q – cytochrome c reductase , biochemistry , cytochrome b , electron transport chain , cytochrome c , demethylation , catalytic cycle , yeast , chemistry , biology , enzyme , gene , mitochondrion , gene expression , mitochondrial dna , dna methylation
The widely accepted catalytic cycle of cytochromes P450 (CYP) involves the electron transfer from NADPH cytochrome P450 reductase (CPR), with a potential for second electron donation from the microsomal cytochrome b 5 /NADH cytochrome b 5 reductase system. The latter system only supported CYP reactions inefficiently. Using purified proteins including Candida albicans CYP51 and yeast NADPH cytochrome P450 reductase, cytochrome b 5 and NADH cytochrome b 5 reductase, we show here that fungal CYP51 mediated sterol 14α‐demethylation can be wholly and efficiently supported by the cytochrome b 5 /NADH cytochrome b 5 reductase electron transport system. This alternative catalytic cycle, where both the first and second electrons were donated via the NADH cytochrome b 5 electron transport system, can account for the continued ergosterol production seen in yeast strains containing a disruption of the gene encoding CPR.