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|Section2= |Section3= }} 12-Hydroxyeicosatetraenoic acid (12-HETE) is a derivative of the 20 carbon polyunsaturated fatty acid, arachidonic acid, containing a Hydroxyl residue at carbon 12 and a 5''Z'',''8Z'',10''E'',14''Z'' Cis–trans isomerism configuration (Z=cis, E=trans) in its four double bonds. It was first found as a product of arachidonic acid metabolism made by human and bovine platelets.〔Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400-4〕〔Biochim Biophys Acta. 1975 Feb 20;380(2):299-307〕 However, the term 12-HETE is ambiquous in that it has been used to indicate not only the initially detected "S" stereoisomer, 12(''S'')-hydroxy-5''Z'',''8Z'',10''E'',14''Z''-eicosatetraenoic acid (12(''S'')-HETE or 12''S''-HETE), made by platelets, but also the later detected ''R'' stereoisomer, 12(''R'')-hydroxy-5''Z'',''8Z'',10''E'',14''Z''-eicosatetraenoic acid (12(''R'')-HETE or 12''R''-HETE) made by other tissues. The two isomers, either directly or after being further metabolized, have been suggested to be involved in a variety of human physiological and pathological reactions. Unlike hormones which are secreted by cells, travel in the circulation to alter the behavior of distant cells, and thereby act as Endocrine signalling agents, these arachidonic acid metabolites act locally as Autocrine signalling agents to regulate the behavior of their cells of origin or as Paracrine signalling agents to regulate the function of nearby cells. In these roles, they may amplify or dampen, expand or contract cellular and tissue responses to disturbances. == Production == In humans, Arachidonate 12-lipoxygenase (12-LO, 12-LOX, ALO12, or platelet type 12-lipoxygenase) is encoded by the ALOX12 gene and expressed primarily in platelets and skin. ALOX12 metabolizes arachidonic acid almost exclusively to 12(''S'')-hydroperoxy-5''Z'',8''Z'',10''E'',14''Z''-eicosatetraenoic acid (12(''S'')-HpETE or 12''S''-HpETE).〔Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:245-62〕 Arachidonate 15-lipoxygenase-1 (15-LO-1, 15-LOX-1, ALOX15), which is expressed in far more tissues that ALOX12, metabolizes arachidonic acid primarily to 15(''S'')-HpETE along with other metabolites of the 15-Hydroxyicosatetraenoic acid family; during this metabolism, however, ALOX15 also forms 12(''S'')-HpETE as a minor product.〔Prog Lipid Res. 2011 Jan;50(1):115-31. 〕 Arachidonate 12-lipoxygenase, 12R type, also termed 12RLOX and encoded by the ALOX12B gene, is expressed primarily in skin and cornea; it metabolizes arachidonic acid to 12(''R'')-HpETE.〔Biochim Biophys Acta. 1993 Feb 24;1166(2-3):258-63〕〔Adv Exp Med Biol. 2002;507:49-53〕 Cytochrome P450 enzymes convert arachidonic acid to a variety of hydroperoxy, epoxy, and dihydroxy derivatives including racemic mixtures of 12(''S'')-HpETE and 12(''R'')-HpETE or 12(''S'')-HETE and 12(''R'')-HETE; the ''R'' stereoisomer predominates in these mixtures.〔〔J Pharmacol Exp Ther. 1998 Jan;284(1):51-60〕〔〔Cancer Metastasis Rev. 2010 Dec;29(4):723-35〕 The initial 12(''S'')-HpETE and 12(''R'')-HpETE products, regardless of their pathway of formation, are rapidly reduced to 12(''S'')-HETE and 12(''R'')-HETE, respectively, by ubiquitous cellular peroxidases, including in particular Glutathione peroxidases〔Biochim Biophys Acta. 2015 Apr;1851(4):383-396. 〕 or, alternatively, are further metabolized as described below. Sub-primate mammals, such as the mouse, rat, rabbit, cow, and pig, express platelet type 12-lipoxygenase but also a leukocyte type 12-lipoxygenase (also termed 12/15-lipoxygenase, 12/15-LOX or 12/15-LO) which is an ortholog of, and metabolically equivalent to, human 15-LO-1 in that it forms predominantly 15(''S'')-HpETE with 12(''S'')-HpETE as a minor product.〔〔Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G948-62. 〕 Mice also express an epidermal type 15-lipoxygenase (e-12LO) which has 50.8% amino acid sequence identity to human 15-LOX-2 and 49.3% sequence indetity to mouse Arachidonate 8-lipoxygenase.〔Biochim Biophys Acta. 1998 Mar 6;1391(1):7-12〕 Mouse e-12LO metabolizes arachidonic acid predominantly to 12(''S'')-HETE and to a lesser extent 15(''S'')-HETE.〔Prostaglandins Other Lipid Mediat. 2001 Jan;63(3):93-107/ref〕〔Prostaglandins Other Lipid Mediat. 2001 Jan;63(3):93-107/ref〕 Sub-human primates, although not extensively examined, appear to have 12-lipoxygenase expression patterns that resemble those of sub-primate mammals or humans depending on the closeness of there genetic relateness to these species.〔Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar;82(2-3):121-9. 〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「12-Hydroxyeicosatetraenoic acid」の詳細全文を読む スポンサード リンク
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