InChI=1S/C23H38O6/c1- 2- 3- 4- 5- 10- 13- 16- 21(29- 27) 17- 14- 11- 8- 6- 7- 9- 12- 15- 18- 23(26) 28- 22(19- 24) 20- 25/h7- 11,13- 14,17,21- 22,24- 25,27H,2- 6,12,15- 16,18- 20H2,1H3/b9- 7- ,11- 8- ,13- 10- ,17- 14+ |
DRKQAMJEQFTELM-VXBMJZGYSA-N |
O=C(CCC/C=C\C\C=C/C=C/C(C/C=C\CCCCC)OO)OC(CO)CO |
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12-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl 2-glyceryl ester
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SUBMITTER
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2-[12-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl]-glycerol
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UniProt
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2-[12-hydroperoxy-(5Z,8Z,10E,14Z)-icosatetraenoyl]-glycerol
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SUBMITTER
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Kozak KR, Gupta RA, Moody JS, Ji C, Boeglin WE, DuBois RN, Brash AR, Marnett LJ (2002) 15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a peroxisome proliferator-activated receptor alpha agonist. The Journal of biological chemistry 277, 23278-23286 (Source: SUBMITTER) [PubMed:11956198] [show Abstract] The recent demonstrations that cyclooxygenase-2 and leukocyte-type 12-lipoxygenase (LOX) efficiently oxygenate 2-arachidonylglycerol (2-AG) prompted an investigation into related oxygenases capable of metabolizing this endogenous cannabinoid receptor ligand. We evaluated the ability of six LOXs to catalyze the hydroperoxidation of 2-AG. Soybean 15-LOX, rabbit reticulocyte 15-LOX, human 15-LOX-1, and human 15-LOX-2 oxygenate 2-AG, providing 15(S)-hydroperoxyeicosatetraenoic acid glyceryl ester. In contrast, potato and human 5-LOXs do not efficiently metabolize this endocannabinoid. Among a series of structurally related arachidonyl esters, arachidonylglycerols serve as the preferred substrates for 15-LOXs. Steady-state kinetic analysis demonstrates that both 15-LOX-1 and 15-LOX-2 oxygenate 2-AG comparably or preferably to arachidonic acid. Furthermore, 2-AG treatment of COS-7 cells transiently transfected with human 15-LOX expression vectors or normal human epidermal keratinocytes results in the production and extracellular release of 15-hydroxyeicosatetraenoic acid glyceryl ester (15-HETE-G), establishing that lipoxygenase metabolism of 2-AG occurs in an eukaryotic cellular environment. Investigations into the potential biological actions of 15-HETE-G indicate that this lipid, in contrast to its free-acid counterpart, acts as a peroxisome proliferator-activated receptor alpha agonist. The results demonstrate that 15-LOXs are capable of acting on 2-AG to provide 15-HETE-G and elucidate a potential role for endocannabinoid oxygenation in the generation of peroxisome proliferator-activated receptor alpha agonists. |
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