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

• Published in: The Journal of biological chemistry Vol. 265; no. 8; pp. 4369 - 4373
• Main Authors: Hadjiagapiou, C, Travers, J B, Fertel, R H, Sprecher, H
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 15-03-1990
• Subjects: Adult; Chromatography, High Pressure Liquid; Diazomethane - pharmacology; Fatty Acids, Unsaturated - metabolism; Humans; Hydroxyeicosatetraenoic Acids - metabolism; Kinetics; Male; Mass Spectrometry; Oxidation-Reduction; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; T-Lymphocytes - metabolism; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)39574-2

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.