Abstract

Cytochrome P450s comprise a superfamily of proteins that catalyze numerous monooxygenase reactions in animals, plants and bacteria. In eukaryotic organisms, these proteins not only carry out reactions necessary for the metabolism of endogenous compounds, but also are important in the oxidation of exogenous drugs and other foreign compounds. Eukaryotic cytochrome P450 system proteins generally reside in membranes, primarily the endoplasmic reticulum or the mitochondrial membrane. These membranes provide a scaffold for the P450 system proteins that facilitate interactions with their redox partners as well as other P450s. This review focuses on the ability of specific lipid components to influence P450 activities, as well as the role of the membrane in P450 function. These studies have shown that P450s and NADPH-cytochrome P450 reductase appear to selectively associate with specific phospholipids, and that these lipid-protein interactions influence P450 activities. Finally, due to the heterogeneous nature of the endoplasmic reticulum as well as other biological membranes, the phospholipids are not arranged randomly, but associate to generate lipid microdomains. Together, these characteristics can affect P450 function by (1) altering the conformation of the proteins, (2) influencing the P450 interactions with their redox partners, and (3) affecting the localization of the proteins into specific membrane microdomains.