title: Metabolism of 15-hydroxy-5,8,11,13-eicosatetraenoic acid by MOLT-4 cells and blood T-lymphocytes.
abstract: 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.
authors.affiliation: Department of Physiological Chemistry, Ohio State University, Columbus 43210.
authors.forename: C
authors.initials: C
authors.lastname: Hadjiagapiou
authors.forename: J B
authors.initials: JB
authors.lastname: Travers
authors.forename: R H
authors.initials: RH
authors.lastname: Fertel
authors.forename: H
authors.initials: H
authors.lastname: Sprecher
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003978:Diazomethane / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D003978:Diazomethane; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C063303:13-hydroxy-6,9,11-octadecatrienoic acid