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Review
. 2013;13(12):1429-40.
doi: 10.2174/15680266113139990110.

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

Katheryne Z Edson  1 , Allan E Rettie
Affiliations
Review

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

Katheryne Z Edson et al. Curr Top Med Chem. 2013.

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.

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Conflict of interest statement

Conflict of interest: None

Figures

Figure 1
Figure 1
The CYP4 enzyme partial I-helix sequence compared to CYP3A4, CYP1A2, and CYP2C9. The conserved glutamic acid residue that forms a covalent bond with the heme cofactor in several CYP4 enzymes is highlighted.
Figure 2
Figure 2
The CYP4F gene cluster on chromosome 19
Figure 3
Figure 3
Fatty acid degradation pathways
See this image and copyright information in PMC

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