Cytochrome gene family

Dalet-Beluche 1, Boulenc X, Eabre G, Maurel P, Bonfils C (1992) Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes. Cross reactivity with human forms. Eur J Biochem 204 641-648 Damaj Ml, Siu EC, Sellers EM, Tyndale RE, Martin BR (2007) Inhibition of nicotine metabolism by methoxysalen Pharmacokinetic and pharmacological studies in mice. J Pharmacol Exp Ther 320 250-257... 

Phase I renders xenobiotics more polar. Oxidation is the most important process of phase I. It is carried out in the endoplasmic reticulum in many tissues by monooxygenases that contain cytochrome P450 (P450-dependent mixed function oxidases) as electron carrier. These enzymes have evolved in the past billion years in response to plant secondary metabolites. There are a number of P450 gene families. 

For proteins that are members of gene families, such as cytochrome P450, available structural models derived from X-ray crystallography and NMR data allow inference of the structure of newly discovered family members. The inference is based on the sequence variations derived from comparing the reference and new DNA sequences. While a high degree of computational power is needed, predictions based on this approach provide preliminary estimates of protein structure without a huge investment in expression, purification, and crystallization. A full structural elucidation requires several years for each protein, even if it can be crystallized. 

Kronbach T, Fischer V, Meyer UA. Cyclosporine metabolism in human liver identification of a cytochrome P450III gene family as the major cyclosporine metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988 43 630-635. 

Lewis, A.D. et al. (1992) Role of cytochrome P-450 from the human CYP3A gene family in the potentiation of morpholino doxorubicin by human liver microsomes, Cancer Res. 52, 4379-4384. Feinstein, E. et al. (1993) Dependence of nucleic acid degradation on in situ free-radical production by Adriamycin, Biochemistry 32, 13156-61. 

COMPLEXITY OF THE CYTOCHROME P450 GENE SUPERFAMILY 9.2.1 CYP Gene Families and Subfamilies... 

Figure 4 Cytochrome P450 superfamily phylogenetic tree showing major gene families.

C. Ioannides and D. V. Parke, Drug Metab. Rev., 22,1 (1990). The Cytochrome P4501 Gene Family of Microsomal Hemoproteins and Their Role in the Metabolic Activation of Chemicals. 

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