Cytochrome P450

Cytochrome P450 monooxygenases (P450s) are versatile biocatalysts that catalyze the regio- and stereospecic oxidation of non-activated hydrocarbons under mild conditions. P450s play a role in the synthesis of many molecules including steroid hormones, certain fats (cholesterol and other fatty acids), and acids used to digest fats (bile acids). There are approximately 60 CYP genes in humans. Cytochrome P450 enzymes (CYPs or P450s) are heme b containing monooxygenases. Heme is a prosthetic group consisting of an iron ion coordinated by four nitrogen atoms of porphyrin. Almost all P450s are external monooxygenases that utilize electrons derived from the pyridine cofactors NADH or NADPH. For catalytic activity P450s must be associated with redox partner proteins that transfer electrons from NAD(P)H to the P450 heme center. The ability of P450s to catalyze the regio-, chemo- and stereospecific oxidation of a vast number of substrates reflects their biological roles and makes them important candidates for scientists to study their role in primary and secondary metabolism, and drug degradation[1].
The enzyme 17α-hydroxylase/C17,20-lyase, for example (CYP17A1; EC 1.14.99.9) is involved in testosterone production. This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.
Acting on paired donor substrates, and using NADH or NADPH as donor, CYP51A1 is the most evolutionarily conserved member of the cytochrome P450 superfamily, and is involved in the metabolism the steroid lanosterol, a precursor of cholesterol. Inhibitors of enzymes of this class of oxidoreductases are frequently applied as antifungal agents. Azole fungicides are broad spectrum antifungal compounds used in agriculture and in human and veterinary medicine. The mechanism of antifungal action relies on inhibition of CYP51, resulting in inhibition of fungal cell growth[2].
CYP2B6 (EC 1.14.14.1) belongs to the class of oxidoreductases that share the common feature of using reduced flavin or flavoprotein as donor in the molecular conversion of substrates. CYP2B6 not only is involved in the  metabolism of nicotine, inhibition may also have a significant effect on the efficacy of other drugs in a wide variety of pathologies that depend on CYP2B6 mediated metabolism (a large number of CYP2B6 substrates including clinically used therapeutics, recreational drugs, endogenous chemicals, pesticides and environmental chemicals have been identified)[3].
Steroidal aromatase (CYP19A1; EC 1.14.14.1) is an enzyme involved in the bio-synthesis of estrogen. Drugs that target  this monooxygenase enzyme may be used for the treatment of a specific type of breast cancer (ER-type, estrogen receptor positive) in post-monopausal women[4].  CYP19A1 belongs to the class of oxidoreductases that share the common feature of using reduced flavin or flavoprotein as donor in the molecular conversion of substrates.


[1] V.B. Urlacher et al. Cytochrome P450 monooxygenases: an update on perspectives for synthetic application. Trends Biotechnol. 2012, 30, 26-36.
[2] Mouse Knockout of the Cholesterogenic Cytochrome P450 Lanosterol 14α-Demethylase (Cyp51) Resembles Antley-Bixler Syndrome. R. Keber et al. Journal of Biological Chemistry 2011, 286, 29086-29097. 
[3] CYP2B6: New Insights into a Historically Overlooked Cytochrome P450 Isozyme. H. Wang, L.M. Tompkins. Curr. Drug. Metab. 2008, 9, 598-610. 
[4] Exemestane: a review of its use in postmenopausal women with breast cancer. E.D. Deeks, L.J. Scott. Drugs. 2009, 69, 889-918. 

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