CYP4F11

Expression

CYP4F11 is expressed in liver, kidney, heart, brain, and skeletal muscle and is overexpressed in ovarian and colon cancers; perhaps relativant to its overexpression in ovarian cancer, its gene has an estrogen receptor α responsive site in its Promoter (genetics) site.

Activities and possible functions

CYP4F11 is active in metabolism of many drugs including benzphetamine, ethylmorphine, chlorpromazine, imipramine, and erythromycin;.

The cytochrome is also able to hydroxylate short-chain and 3-hydroxylated medium chain fatty acids by attaching a hydroxyl residue to their terminal carbon by omega oxidation in a reaction that may be critical to the processing of these fatty acids. It likewise omega-hydroxylates Vitamin Ks including menaquinone in a metabolic step which is essential for their further metabolism by beta oxidation and probably thereby their removal by catabolism to regulate their tissue levels.

CYP4F11 omega-hydroxylates leukotriene B4 (LTB4) to 20-hydroxy-LTB4, 5-Hydroxyicosatetraenoic acid (5-HETE) to 20-hydroxy-5-HETE (i.e. 5,20-diHETE), 12-hydroxyeicosatetraenoic acid (12-HETE) to 12,20-diHETE, lipoxins and possibly 5-oxo-eicosatetraenoic acid (5-oxo-ETE) to their 20-hydroxy metabolites; these reactions begin the inactivation of these pro- (LTB4, 5-HETE, 12-HETE, and 5-oxo-ETE) and anti- (lipoxins) cell signaling agents; however, it is relatively weak compared to, and therefore possibly not as physiologically relevant as, other CYP4Fs such as CYP4F2, CYP4F3a, CYP4F3b, CYP4A11 and CYP4F2 in doing so. The enzyme also hydroxylates arachidonic acid (i.e. eicosatetraenoic acid to 20-Hydroxyeicosatetraenoic acid) (20-HETE) although other cytochromes such as CYP4A11 and CYP4F2 appear more important in this metabolic conversion. 20-HETE is a short-lived potent signaling agent that functions to regulate blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans. Gene polymorphism variants of CYP4A11 are associated with the development of hypertension and cerebral infarction (i.e. ischemic stroke) in humans (see 20-Hydroxyeicosatetraenoic acid). In spite of its relative impotency and/or importance in accomplishing these omega-hydroxylations, CYP4F11 may contribute to them in certain tissues.

References

References

1. (September 2000). "A novel human cytochrome P450 4F isoform (CYP4F11): cDNA cloning, expression, and genomic structural characterization". Genomics.
2. "Entrez Gene: CYP4F11".
3. (June 2008). "Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases". Biochemical Pharmacology.
4. (2015). "Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer".
5. (July 2015). "Vascular actions of 20-HETE". Prostaglandins & Other Lipid Mediators.
6. (January 2005). "Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension". Circulation.
7. (August 2008). "Association of a CYP4A11 variant and blood pressure in black men". Journal of the American Society of Nephrology.
8. (March 2008). "A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men". Journal of Hypertension.
9. (October 2005). "Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy". Hypertension.
10. (December 2008). "A polymorphism regulates CYP4A11 transcriptional activity and is associated with hypertension in a Japanese population". Hypertension.
11. (March 2010). "Association of common variants of CYP4A11 and CYP4F2 with stroke in the Han Chinese population". Pharmacogenetics and Genomics.