20-Hydroxyeicosatetraenoic acid
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IUPAC name
(5Z,8Z,11Z,14Z)-20-Hydroxyicosa-5,8,11,14-tetraenoic acid
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| Other names
20-HETE, 20-Hydroxy-5,8,11,14-eicosatetraenoic, 20-Hydroxyeicosatetraenoic acid
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3D model (Jmol)
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| MeSH | acid 20-hydroxy-5,8,11,14-eicosatetraenoic acid |
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PubChem CID
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| Properties | |
| C20H32O3 | |
| Molar mass | 320.47 g·mol−1 |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, Hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast.
A subset of (CYP450) microsome-bound ω-hydroxylases, the , metabolize arachidonic acid to 20-HETE by an omega oxidation reaction. CYP450 enzymes belong to a superfamily which in humans is composed of at least 57 members and in mice at least 120 members. Among this superfamily, certain members of the CYP4A and CYP4F subfamilies in the CYP4 family are considered predominant cytochrome P450 enzymes that are responsible in most tissues for forming 20-HETE and, concurrently, smaller amounts of 19-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (19-HETE). However, CYP2U1 may also contribute to the production of these two HETEs and CYP4F8 can metabolize arachidonic acid to 19-HETE while forming little or no 20-HETE.
The production of 19-HETE with 20-HETE may be significant since 19(R)-HETE, although not its stereoisomer, 19(S)-HETE, inhibits the action of 20-HETE on vascular endothelial cells. Based on studies analyzing the production of other HETEs by CYP enzymes, the production of 19-HETE by these enzymes may include both its R and S stereoisomers.
In humans, the CYP4 ω-hydroxylases include CYP4A11, CYP4F2, and CYP4F3 with the predominant 20-HETE-synthesizing enzymes being CYP4F2, which is the major 20-HETE producing enzyme in the human kidney, followed by CYP4A11. CYP4F3 is expressed as two distinct enzymes, CYP4F3A and CYP4F3B, due to alternative splicing of a single pre-mRNA precursor molecule; CYP4F3A is mostly expressed in leukocytes, CYP4F3B mostly in the liver. Human CYP4Z1, which is expressed in a limited range of tissues such as human breast and ovary, may also metabolize arachidonic acid to 20-HETE while human CYP4A22, once considered as contributing to 20-HETE production, is now regarded as being metabolically inactive. Finally, CYP2U1, the only member of the human CYP2U subfamily, is highly expressed in brain and thymus and to lesser extents in numerous other tissues such as kidney, lung and heart. CYP2U1 protein is also highly expressed, compared to several other cytochrome P450 enzymes, in malignant breast tissue; the MCF-7 human breast cancer cell line express messenger RNA for this cytochrome.
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