Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase.
The demonstration of in vivo arachidonic acid epoxidation and omega-hydroxylation established the cytochrome P450 epoxygenase and omega/omega-1 hydroxylase as formal metabolic pathways and as members of the arachidonate metabolic cascade. The characterization of the potent biological activities associated with several of the cytochrome P450-derived eicosanoids suggested new and important functional roles for these enzymes in cellular, organ, and body physiology, including the control of vascular reactivity and systemic blood pressures. Past and current advances in cytochrome P450 biochemistry and molecular biology facilitate the characterization of cytochrome P450 isoforms responsible for tissue/organ specific arachidonic acid epoxidation and omega/omega-1 hydroxylation, and thus, the analysis of cDNA and/or gene specific functional phenotypes. The combined application of physiological, biochemical, molecular, and genetic approaches is beginning to provide new insights into the physiological and/or pathophysiological significance of these enzymes, their endogenous substrates, and products.
Capdevila
J H
JH
Departments of Medicine, Vanderbilt University Medical School, Nashville, TN 372323, USA.
Falck
J R
JR
Harris
R C
RC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D006899:Mixed Function Oxygenases; D009249:NADP / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D015777:Eicosanoids; D016718:Arachidonic Acid; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C033914:Cyp2b19 protein, mouse; D000090762:Cytochrome P-450 CYP2J2; D000072467:Cytochrome P450 Family 2