Leukotriene-B(4) omega-hydroxylase 2 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''CYP4F3''
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 ...
.
CYP4F3 encodes two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the
alternative splicing of a single pre-mRNA precursor molecule; selection of either isoform is tissue-specific with CYP3F3A being expressed mostly in
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
and CYP4F3B mostly in the liver.
Function
The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids and other lipids. CYP4F3 actually encodes two splice-variants, CYP4F3A and CYP4F3B, of the cytochrome P450 superfamily of enzymes. The gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away.
Both variants localize on the
endoplasmic reticulum and metabolize
leukotriene B4
Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice.
Biochemistry
Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in r ...
and very likely
5-hydroxyeicosatetraenoic acid,
5-oxo-eicosatetraenoic acid, and
12-hydroxyeicosatetraenoic acid by an
omega oxidation Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. It is an alternative pathway to beta oxidation that, instead of involving the β carbon, involves the oxidation of the ω carbon (the carbon most dist ...
reaction, i.e. by adding 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 hydro ...
residue to their terminal (i.e. C-20) carbon. This addition starts the process of inactivating and degrading all of these well-known mediators of
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
CYP3FA is the major enzyme accomplishing these omega oxidations in leukocytes.
CYP4F3A and/or CYP43FB also omega oxidize
arachidonic acid to
20-Hydroxyeicosatetraenoic acid (20-HETE) as well as
epoxyeicosatrienoic acids (EETs) to 20-hydroxy-EETs.
20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans;
it has also been proposed to be involved in regulating the growth of various types of human cancers (see
20-Hydroxyeicosatetraenoic acid#Cancer). EETS have a similar set of regulatory functions but often act in a manner opposite to 20-HETE (see
epoxyeicosatrienoic acid#Cancer); since, however, the activities of the 20-HEETs have not been well-defined, the function of EET omega oxidation is unclear.
Genetic Variants
The hydroxylation-induced inactivation of the mediators of inflammation, perhaps particularly of leukotriene B4, may underlie the proposed roles of these cytochromes in dampening inflammatory responses as well as the reported associations of certain CYP4F3
single nucleotide variant
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
s (SNPs) with human
Crohn's disease (SNPs are designated rs1290617
and rs1290620
and
Celiac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
(rs1290622 and rs1290625).
There is also a study that have found an association within Guangzhou population between the single nucleotide variation rs3794987 and susceptibility to the SARS-CoV-1 virus, discovered in 2003. The GG/AG genotype was associated with an increased susceptibility to SARS-CoV-1, comparing to the AA genotype. However, the results of this association were not replicated in another study, on the Beijing population. The combined analysis of the two studies does not show any association of the CYP4F3 SNPs analyzed with SARS-CoV-1 susceptibility.
References
Further reading
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