JBC Avanti Polar Lipids

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J. Biol. Chem., Vol. 265, Issue 8, 4369-4373, Mar, 1990

Metabolism of 15-hydroxy-5,8,11,13-eicosatetraenoic acid by MOLT-4 cells and blood T-lymphocytes

C Hadjiagapiou, JB Travers, RH Fertel and H Sprecher
Department of Physiological Chemistry, Ohio State University, Columbus 43210.

MOLT-4 lymphocytes metabolize 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) via beta-oxidation with retention of the hydroxyl group at the omega 6-carbon atom. 15-HETE oxidation is accompanied by the time-dependent accumulation of both beta-hydroxy acids and metabolites produced by repetitive cycles of the beta-oxidation spiral. Detection of 7-hydroxy-5-dodecenoic acid shows that these cells continue to beta- oxidize the substrate when the conjugated diene is allylic to a hydroxyl group. When 15-HETE was the substrate, it was also possible to detect 12-hydroxy-5,8,10-heptadecatrien-1-al and 3,15-dihydroxy-8,11,13- eicosatrienoic acid. The former product may be produced by alpha- oxidation of 13-hydroxy-6,9,11-octadecatrienoic acid followed by its decarboxylation. Detection of a 20-carbon metabolite, lacking a double bond at position 5, suggests that an intermediate of beta-oxidation was used as a substrate for chain elongation. When 13-hydroxy-6,9,11- octadecatrienoic acid was used as a substrate, it was indeed possible to detect 3,15-dihydroxy-8,11,13-eicosatrienoic acid as well as 15- hydroxy-8,11,13-eicosatrienoic acid. In addition, 13-hydroxy-6,9,11- octadecatrienoic acid was a precursor for the biosynthesis of both 14- hydroxy-7,10,12-nonadecatrien-1-al and 1,14-dihydroxy-7,10,12- nonadecatriene. These studies with MOLT-4 cells as well as with T- lymphocytes isolated from blood show that products of the 15- lipoxygenase pathway are metabolized with the accumulation of a variety of compounds. Since 15-HETE has been implicated as a modulator of T- cell function, these findings raise the possibility that the newly described metabolites may be involved in regulating lymphocyte function.
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D. L. Luthria, S. P. Baykousheva, and H. Sprecher
Double Bond Removal from Odd-numbered Carbons during Peroxisomal [IMAGE]-Oxidation of Arachidonic Acid Requires both 2,4-Dienoyl-CoA Reductase and [IMAGE][IMAGE],[IMAGE][IMAGE]-Dienoyl-CoA Isomerase
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