Cytochromes p450: roles in diseases

Abstract

The cytochrome P450 superfamily consists of a large number of heme-containing monooxygenases. Many human P450s metabolize drugs used to treat human diseases. Others are necessary for synthesis of endogenous compounds essential for human physiology. In some instances, alterations in specific P450s affect the biological processes that they mediate and lead to a disease. In this minireview, we describe medically significant human P450s (from families 2, 4, 7, 11, 17, 19, 21, 24, 27, 46, and 51) and the diseases associated with these P450s.

Keywords: Cholesterol Metabolism; Cytochrome P450; Eicosanoid; Enzyme Mutation; Genetic Diseases; Genetic Polymorphism; Inborn Errors of Metabolism; Steroidogenesis.

FIGURE 1.

Pathways and cytochrome P450 enzymes involved in the biosynthesis and metabolism of different sterols (A) and metabolism of arachidonic acid (B). Coloring of P450s is based on the pathway, i.e. cholesterol-related P450s are shown in magenta, steroidogenic P450s are shown in green, P450s of vitamin D₃ activation and inactivation are shown in light blue, and P450s metabolizing arachidonic acid are shown in orange. If several P450s utilize the same substrate, that shown in boldface is responsible for the majority of substrate metabolism.