P450 enzymes in lipid oxidation

Abstract

Through gene duplication and natural selection, the ancestral cytochrome P450 gene evolved to perform many essential functions in higher organisms. The role of P450 enzymes in metabolizing steroids, hormones, and xenobiotic chemicals is well established. More recently, members of several P450 subfamilies were found to be expressed in cardiovascular tissues and active in the metabolism endogenous fatty acids to oxidized lipids. These fatty acids, such as arachidonic acid, are released from cell membranes by phospholipases and mono-oxidized to epoxides called epoxyeicosatrienoic acids (EETs) or hydroxyls called hydroxyeicosatetraenoic acids (HETEs) by CYP2 and CYP4 family members. After generation of prostaglandin H2 by cyclooxygenases, CYP5 and CYP8 enzymes perform isomerase reactions to act as terminal synthases for thromboxane and prostacyclin production. The biologically active eicosanoids and related compounds play important roles in cardiovascular homeostasis and pathology. This chapter discusses the reactions, regulation, localization, and physiological consequences of this extrahepatic cytochrome P450 expression and activity.