CYP4F11 (cytochrome P450, family 4, subfamily F, polypeptide 11) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that in humans is encoded by the ''CYP4F11''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This gene encodes a member of the

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

superfamily of

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

s. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F2, is approximately 16 kb away.

Alternatively spliced Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be i ...

transcript variants encoding the same protein have been found for this gene.

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) In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of ...

site.

Activities and possible functions

CYP4F11 is active in metabolism of many drugs including benzphetamine, ethylmorphine,

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...

imipramine Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. The drug is also used to treat bedwetting. ...

, and

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used du ...

;. The cytochrome is also able to hydroxylate short-chain and 3-hydroxylated medium chain

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...

s by attaching a

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...

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 K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulat ...

s including menaquinone in a metabolic step which is essential for their further metabolism by

beta oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cyc ...

and probably thereby their removal by

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids ...

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 In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

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 A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to ge ...

variants of CYP4A11 are associated with the development of hypertension and

cerebral infarction A cerebral infarction is the pathologic process that results in an area of necrotic tissue in the brain (cerebral infarct). It is caused by disrupted blood supply (ischemia) and restricted oxygen supply (hypoxia), most commonly due to thromboemb ...

(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.

Expression

Activities and possible functions

Further reading

References

External links

Further reading