The roles of cytochrome b5 in cytochrome P450 reactions

J Biochem Mol Toxicol. 2002;16(6):311-6. doi: 10.1002/jbt.10052.


Cytochrome b(5), a 17-kDa hemeprotein associated primarily with the endoplasmic reticulum of eukaryotic cells, has long been known to augment some cytochrome P450 monooxygenase reactions, but the mechanism of stimulation has remained controversial. Studies in recent years have clarified this issue by delineating three pathways by which cytochrome b(5) augments P450 reactions: direct electron transfer of both required electrons from NADH-cytochrome b(5) reductase to P450, in a pathway separate and independent of NADPH-cytochrome P450 reductase; transfer of the second electron to oxyferrous P450 from either cytochrome b(5) reductase or cytochrome P450 reductase; and allosteric stimulation of P450 without electron transfer. Evidence now indicates that each of these pathways is likely to operate in vivo.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation / physiology
  • Animals
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome Reductases / metabolism
  • Cytochrome-B(5) Reductase
  • Cytochromes b5 / metabolism*
  • Electron Transport
  • Endoplasmic Reticulum / metabolism
  • Ferrous Compounds / metabolism
  • Glucocorticoids / biosynthesis
  • Gonadal Steroid Hormones / biosynthesis
  • Humans
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Oxidation-Reduction


  • Ferrous Compounds
  • Glucocorticoids
  • Gonadal Steroid Hormones
  • Cytochromes b5
  • Cytochrome P-450 Enzyme System
  • Cytochrome Reductases
  • Cytochrome-B(5) Reductase
  • NADPH-Ferrihemoprotein Reductase