Cytochrome P450 Evolution and Nomenclature

  • F. J. Gonzalez
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


The evolution of cytochromes P450 has been thoroughly discussed in a number of reviews (Nebert and Gonzalez 1987; Nelson and Strobel 1987; Gonzalez and Nebert 1990). All cytochrome P450 proteins possess a non-covalently bound heme (protoporphyrin IX) and segment of 26 amino acids surrounding a cysteine that is highly conserved. This cysteine donates the thiolate fifth ligand to the heme iron. The amino acid environment surrounding the heme results in a typical cytochrome P450 Soret absorption band at around 450 nm when the iron is reduced by electrons and complexed with carbon monoxide. Any enzyme having these properties would be a “card-holding” member of the cytochrome P450 superfamily.


Cytochrome P450 Gene Cytochrome P450 Protein Amino Acid Environment Cytochrome P450 Superfamily Molecular Drive 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bale AE, Mitchell AL, Gonzalez FJ, McBride OW (1991) Localization of the CYP2F1 gene by multi-point linkage analysis and pulsed field gel electrophoresis. Genomics 10: 284–286PubMedCrossRefGoogle Scholar
  2. Brooks B, McBride OW, Dolphin CT, Farrall M, Scambler P, Gonzalez FJ, Idle JR (1988) The gene CYP3 encoding P450PCN1 (nifedipine oxidase) is tightly linked to the gene COLIA2 encoding collagen type I alpha on 7q21–q22.1. Am J Hum Genet 43: 280–284PubMedGoogle Scholar
  3. Caporaso N, Landi MT, Vineis P (1991) Relevance of metabolic polymorphisms to human carcinogenesis: evolution of epidemiological evidence. Pharmacogenetics 1: 4–19PubMedCrossRefGoogle Scholar
  4. Dayhoff MO (1979) Atlas of protein sequence and structure, vol 5, suppl 3. National Biomedical Research Foundation, Silver SpringGoogle Scholar
  5. Dover GA (1987) DNA turnover and the molecular clock. J Mol Evol 26: 47–58PubMedCrossRefGoogle Scholar
  6. Dover GA (1989) Slips, strings and species. Trends Genet 5: 100–102PubMedCrossRefGoogle Scholar
  7. Eichelbaum M, Gross AS (1990) The genetic polymorphism of debrisoquine/sparteine metabolism - clinical aspects. Pharmacol Ther 46: 377–394PubMedCrossRefGoogle Scholar
  8. Evans DAP (1989) N-acetyltransferase. Pharmacol Ther 47: 152–234Google Scholar
  9. Gonzalez FJ (1991) Cytochrome P-450. In: Dulbecco R (ed) Encyclopedia of human biology, vol 2. Academic, New York, p 737Google Scholar
  10. Gonzalez FJ, Nebert DW (1990) Evolution of the P450 gene superfamily: animal plant “warfare”, molecular drive and human genetic differences in drug oxidation. Trends Genet 6: 182–186PubMedCrossRefGoogle Scholar
  11. Gonzalez FJ, Matsunaga T, Nagata K, Meyer UA, Nebert DW, Pastekwa J, Kozak CA, Gillette J, Gelboin HV, Hardwick JP (1987) Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily, regulation, chromosome mapping, and molecular analysis of the DA rat polymorphism. DNA 6: 149–161PubMedCrossRefGoogle Scholar
  12. Gonzalez FJ, Crespi CL, Gelboin HV (1991) cDNA-expressed human cytochrome P450: a new age of molecular toxicology and human risk assessment. Mutat Res 247: 113–127Google Scholar
  13. Matsunaga E, Zeugin T, Zanger UM, Aoyama T, Meyer UA, Gonzalez FJ (1990) Sequence requirements for cytochrome P450IID1 catalytic activity: a single amino acid change (IIe380 → Phe) specifically decreases Vmax of the enzyme for bufuralol but not debrisoquine hydroxylation. J Biol Chem 265: 17197–17201PubMedGoogle Scholar
  14. Motulsky AG (1964) Pharmacogenetics. Prog Med Genet 3: 49–100Google Scholar
  15. Nebert DW (1991) Proposed role of drug-metabolizing enzymes: regulation of steady-state levels of the ligands that effect growth, homeostasis, differentiation and neuroendocrine functions. Mol Endocrinol 5: 1203–1214PubMedCrossRefGoogle Scholar
  16. Nebert DW, Gonzalez FJ (1985) Cytochrome P-450 gene expression and regulation. Trends Pharmacol Sci 6: 160–164CrossRefGoogle Scholar
  17. Nebert DW, Gonzalez FJ (1987) P450 genes: structure, evolution and regulation. Annu Rev Biochem 56: 945–993PubMedCrossRefGoogle Scholar
  18. Nebert DW, Nelson DR (1991) P450 gene nomenclature based on evolution. Methods Enzymol 206: 3–11PubMedCrossRefGoogle Scholar
  19. Nebert DW, Weber WW (1990) Pharmacogenetics. In: Pratt WB, Taylor P (eds) Principles of drug action. The basis of pharmacology, 3rd edn. Churchill Livingstone, New York, pp 469–531Google Scholar
  20. Nebert DW, Nelson DR, Feyereisen R (1989) Evolution of the cytochrome P450 genes. Xenobiotica 19: 1149–1160PubMedCrossRefGoogle Scholar
  21. Nebert DW, Nelson DR, Coon MJ, Estabrook RW, Feyereisen R, Fujii-Kuriyama Y, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, Loper JC, Sato R, Waterman MR, Waxman DJ (1991) The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 10: 1–14PubMedCrossRefGoogle Scholar
  22. Nelson DR, Strobel HW (1987) Evolution of cytochrome P-450 proteins. Mol Biol Evol 4: 572–593PubMedGoogle Scholar
  23. Nelson DR, Kamataki T, Waxman DJ, Guengerich FP, Estabrook RW, Feyereisen R, Gonzalez FJ, Coon MJ, Gunsalus IC, Gotoh O, Okuda K, Nebert DW (1993) The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 12: 1–70PubMedCrossRefGoogle Scholar
  24. Ruettinger RT, Wen LP, Fulco AJ (1989) Coding nucleotide, 5′ regulatory and deduced amino acid sequences of P-450BM3, a single peptide cytochrome P-450: NADPH-P-450 reductase from Bacillus megaterium. J Biol Chem 264: 10987–10995PubMedGoogle Scholar
  25. Sneath PHA, Sokal RR (1973) Numerical taxonomy. Freeman, San Francisco.Google Scholar
  26. Van Etten HD, Mathews DE, Mathews PS (1989) Phytoalexin detoxification: importance for the pathogenicity and practical implications. Annu Rev Phytopathol 27: 143–164.CrossRefGoogle Scholar
  27. Williams RT (1974) Inter-species variations on the metabolism of xenobiotics. Biochem Soc Trans 2: 359–377Google Scholar
  28. Yamano S, Aoyama T, McBride OW, Hardwick JP, Gelboin HV, Gonzalez FJ (1989) Human NADPH-P450 oxidoreductase: complementary DNA cloning, sequence and vaccinia virus-mediated expression and localization of the CYPOR gene to chromosome 7. Mol Pharmacol 35: 83–88Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • F. J. Gonzalez

There are no affiliations available

Personalised recommendations