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J. Biol. Chem., Vol. 265, Issue 8, 4369-4373, Mar, 1990
C Hadjiagapiou, JB Travers, RH Fertel and H Sprecher
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.
Metabolism of 15-hydroxy-5,8,11,13-eicosatetraenoic acid by MOLT-4 cells and blood T-lymphocytes
Department of Physiological Chemistry, Ohio State University, Columbus 43210.
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