12-Hydroxyheptadecatrienoic acid
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IUPAC name
(5Z,8E,10E,12S)-12-Hydroxy-5,8,10-heptadecatrienoic acid
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3D model (Jmol)
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| ChemSpider | |
| ECHA InfoCard | 100.161.462 |
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PubChem CID
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| Properties | |
| C17H28O3 | |
| Molar mass | 280.41 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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| Infobox references | |
12-Hydroxyheptadecatrenoic acid (also termed 12-HHT, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, or 12(S)-HHTrE) is a 17 carbon metabolite of the 20 carbon polyunsaturated fatty acid, arachidonic acid. It was first detected and structurally defined by P. Wlodawer, B. Samuelsson, and M. Hamberg as a product of arachidonic acid metabolism made by microsomes (i.e. endoplasmic reticulum) isolated from sheep seminal vesicle glands and by intact human platelets. 12-HHT is less ambiguously termed 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid to indicate the S stereoisomerism of its 12-hydroxyl residue and the Z, E, and E cis-trans isomerism of its three double bonds. The metabolite was for many years thought to be merely a biologically inactive byproduct of prostaglandin synthesis. More recent studies, however, have attached potentially important activity to it.
Cyclooxygenase-1 and cyclooxygenase-2 metabolize arachidonic acid to the 15-hydroperoxy, 20 carbon prostaglandin (PG) intermediate, PGG2, and then to the 15-hydroxy, 20 carbon intermediate, prostaglandin H2 (PGH2). Thromboxane synthase further metabolizes PGH2 to the 20 carbon product, Thromboxane A2, the 17 carbon product, 12-HHT, and the 3 carbon product Malonyldialdehyde. Platelets express cycloxygenase and thromboxane synthase enzymes, producing PGG2, PGH2, and TXA2 in response to platelet aggregating agents such as thrombin; these metabolites act as by feeding back to promote further aggregation of their cells of origin and as paracrines by recruiting nearby platlets into the response as well as exerting effects on other nearby tissues such as contracting blood vessels. These effects combine to trigger blood clotting and limiting blood loss. 12-HHT is a particularly abundant product of these pro-clotting responses, accounting for about one third of the total amount of arachidonic acid metabolites formed by physiologically stimulated human platelets. Its abundant production during blood clotting, the presence of cyclooxygenases and to a lesser extent thromboxane synthase in a wide range of cell types and tissue, and its production by other pathways imply that 12-HHT has one or more important bioactivities relevant to clotting and, perhaps, other responses.
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