Cytochromes P450, Drugs, and Diseases

Table 1.

Endogenous Subtrates of P450s

Substrates	P450	Reference
^a CYP2D6 and CYP3A4 are also hypothesized to act in cholesterol and bile acid metabolism.
^b The six P450s named here are primarily steroidogenic. CYP1A2, CYP1B1, and CYP3A4, which act on xenobiotics, may contribute to steroid catabolism. CYP11A1, CYP11B1, and CYP11B2 are mitochondrial enzymes.
^c CYP5A1 and CYP8A1 are commonly known as thromboxane synthase and prostaglandin synthase, respectively. CYP4F2, CYP4F3, and CYP4F8 can also hydroxylate eicosinoids.
^d Congenital defects in CYP27B1 are linked to rickets.
^e Of particular interest is the oxidation of arachidonate and other unsaturated fatty acids to form biologically active (e.g., affecting blood pressure) epoxides and ω -hydroxy derivatives.
^f Unlike the P450s named in the other four classes, expression of P450s that act on “other eicosanoids” has not been implicated in human disease.
Cholesterol and bile acids	CYP7A1, CYP7B1, CYP8B1, CYP27A1, CYP39A1, CYP46A1, CYP51^a	(7)
Steroids	CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, CYP21A2^b	(14, 15)
Prostaglandins	CYP5A1, CYP8A1^c;	(16, 17)
Vitamins A and D	CYP24A1, CYP26A1, CYP26B1, CYP27A1, CYP27B1d	(8)
Other eicosanoidse	CYP2C8, CYP2C9, CYP2J2, CYP4A11, CYP4B1, CYP4F2, CYP4F3, and CYP4F8^f	(12, 13)