Title:CYP4 Enzymes As Potential Drug Targets: Focus on Enzyme Multiplicity, Inducers and Inhibitors, and Therapeutic Modulation of 20- Hydroxyeicosatetraenoic Acid (20-HETE) Synthase and Fatty Acid ω- Hydroxylase Activities
Volume: 13
Issue: 12
Author(s): Katheryne Z. Edson and Allan E. Rettie
Affiliation:
Keywords:
20-HETE, CYP4, HET0016, hypertension, stroke, cancer, Refsum disease, X-ALD.
Abstract: The Cytochrome P450 4 (CYP4) family of enzymes in humans is comprised of thirteen isozymes that typically
catalyze the ω-oxidation of endogenous fatty acids and eicosanoids. Several CYP4 enzymes can biosynthesize 20-
hydroxyeicosatetraenoic acid, or 20-HETE, an important signaling eicosanoid involved in regulation of vascular tone and
kidney reabsorption. Additionally, accumulation of certain fatty acids is a hallmark of the rare genetic disorders, Refsum
disease and X-ALD. Therefore, modulation of CYP4 enzyme activity, either by inhibition or induction, is a potential
strategy for drug discovery. Here we review the substrate specificities, sites of expression, genetic regulation, and inhibition
by exogenous chemicals of the human CYP4 enzymes, and discuss the targeting of CYP4 enzymes in the development
of new treatments for hypertension, stroke, certain cancers and the fatty acid-linked orphan diseases.
