CYP2U1 (cytochrome P450, family 2, subfamily U, polypeptide 1) 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, respo ...

that in humans is encoded by the ''CYP2U1''

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 ba ...

Function

This gene encodes a member of the

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

superfamily of enzymes. The cytochrome P450 proteins are

monooxygenase Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation o ...

s which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and the hydroxylation of fatty acids and fatty acid metabolites. CYP2U1 metabolized arachidonic acid,

docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-lino ...

(DHA), and other long chain

fatty acid 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, fr ...

s which suggests that CYP2U1 may play a role in brain and immune functions. CYP2U1 also metabolizes propanone,

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

, and 2-oxypropane.

Tissue distribution

The CYP2U1 gene is a highly conserved gene that is mainly expressed in brain and thymus, but also at lower levels in kidney, lung, and heart.

Reactions

CYP2U1 hydroxylates arachidonic acid,

(DHA), and other long chain

s at their terminal (i.e., ω) carbon to form 20-hydroxy-arachidonic acid (i.e.

20-Hydroxyeicosatetraenoic acid 20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5''Z'',8''Z'',11''Z'',14''Z''-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regula ...

or 20-HETE), 22-hydroxy-docosahexaneoic acid, and other ω-hydroxy long chain fatty acids, respectively, plus lesser amounts of these fatty acids ω-1 hydroxy metabolites, i.e. 19-HETE, 21-hydroxy-docosahexaenoic acid, and other ω-1 hydroxy long chain fatty acids, respectively. One of these metabolites, 20-HETE, is a regulator of blood pressure and blood flow to organs in animal models and, based on genetic studies, possibly in humans (see

Clinical significance

A mutation (c.947A>T) in CYP2U1 has been associated in a very small number of patients with

hereditary spastic paraplegia Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditar ...

in that it segregates with the disease at the homozygous state in two afflicted families. This mutation affects an amino acid (p.Asp316Val) that is highly conserved among CYP2U1

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

as well as other cytochrome P450 proteins; this p.Asp314Val mutation is located in the enzyme's functional domain, is predicted to be damaging to the enzyme's activity, and is associated with

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

dysfunction. A second homozygous enzyme-disabling mutation has been identified in CYP2U1, c.1A>C/p.Met1?, that is associated with <1% of hereditary spastic paraplegia sufferers. The reduction in 20-HETE production by these mutations, and thereby in 20-HETE's activation of the

TRPV1 The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...

neural receptor, it is hypothesized, may contribute to the development of this disease (see

for details). CYPU21 along with members of the CYP4A and CYP4F sub-families also ω-hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including

LTB4 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 respon ...

, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...

that are involved in regulating various inflammatory, vascular, and other responses in animals and humans. This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 and 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 with human Krohn's disease and

Coeliac 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 ...

, respectively.

Function

Tissue distribution

Reactions

Clinical significance

References

External links

Further reading