title: Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer.
abstract: Cytochrome P450-dependent ω-hydroxylation is a prototypic metabolic reaction of CYP4 family members that is important for the elimination and bioactivation of not only therapeutic drugs, but also endogenous compounds, principally fatty acids. Eicosanoids, derived from arachidonic acid, are key substrates in the latter category. Human CYP4 enzymes, mainly CYP4A11, CYP4F2, and CYP4F3B, hydroxylate arachidonic acid at the omega position to form 20-HETE, which has important effects in tumor progression and on angiogenesis and blood pressure regulation in the vasculature and kidney. CYP4F3A in myeloid tissue catalyzes the ω-hydroxylation of leukotriene B4 to 20-hydroxy leukotriene B4, an inactivation process that is critical for the regulation of the inflammatory response. Here, we review the enzymology, tissue distribution, and substrate selectivity of human CYP4 ω-hydroxylases and their roles as catalysts for the formation and termination of the biological effects of key eicosanoid metabolites in inflammation and cancer progression.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Johnson
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA; Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Katheryne Z
authors.initials: KZ
authors.lastname: Edson
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA.
authors.forename: Rheem A
authors.initials: RA
authors.lastname: Totah
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA. Electronic address: rettie@uw.edu.
authors.forename: Allan E
authors.initials: AE
authors.lastname: Rettie
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*
chemical_list: D015777:Eicosanoids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D042926:Cytochrome P-450 CYP4A; C409986:cytochrome P-450 omega-hydroxylase
keywords: 20-HETE; Arachidonic acid; CYP4; Cancer; Cytochrome P450; Eicosanoids; Fatty acids; Inflammation; Leukotrienes; Omega-hydroxylases