TY - JOUR
T1 - Formation of a novel arachidonic acid metabolite in peroxisomes
AU - Gordon, J. A.
AU - Heller, S. K.
AU - Rhead, W. J.
AU - Watkins, P. A.
AU - Spector, A. A.
N1 - Funding Information:
Support for these studies was provided by grants HL 49264 (AAS), DK 28516 (AAS), DK 33289 (WJR), and HD 24061 (PAW) from the National Institutes of Health, and Grant-in-aid IA-92-GS-37 (JAG) from the Iowa Affiliate, American Heart Association.
PY - 1995
Y1 - 1995
N2 - A new radiolabeled metabolite was released into the extracellular fluid by normal human skin fibroblasts that were labeled with [5,6,8,9,11,12,14,15-3H] arachidonic acid. This product continued to accumulate during a 24 h incubation, and its formation was not saturated at arachidonic acid concentrations up to 15 μmol/L. The compound, identified as hexadecatrienoic acid, was not produced by Zellweger fibroblasts which are deficient in peroxisomal fatty acid β-oxidation. By contrast, radiolabeled hexadecatrienoic acid was produced by mutant fibroblasts having other peroxisomal defects, including X-linked adrenoleukodystrophy, adult Refsum's disease, and rhizomelic chondrodysplasia punctata. This radiolabeled metabolite also was produced by mutant fibroblasts that cannot oxidize long-chain fatty acids in the mitochondria. These results indicate that hexadecatrienoic acid is synthesized from arachidonic acid by peroxisomal β-oxidation. The absence of this pathway may account for some of the biochemical and functional abnormalities that occur in Zellweger's syndrome.
AB - A new radiolabeled metabolite was released into the extracellular fluid by normal human skin fibroblasts that were labeled with [5,6,8,9,11,12,14,15-3H] arachidonic acid. This product continued to accumulate during a 24 h incubation, and its formation was not saturated at arachidonic acid concentrations up to 15 μmol/L. The compound, identified as hexadecatrienoic acid, was not produced by Zellweger fibroblasts which are deficient in peroxisomal fatty acid β-oxidation. By contrast, radiolabeled hexadecatrienoic acid was produced by mutant fibroblasts having other peroxisomal defects, including X-linked adrenoleukodystrophy, adult Refsum's disease, and rhizomelic chondrodysplasia punctata. This radiolabeled metabolite also was produced by mutant fibroblasts that cannot oxidize long-chain fatty acids in the mitochondria. These results indicate that hexadecatrienoic acid is synthesized from arachidonic acid by peroxisomal β-oxidation. The absence of this pathway may account for some of the biochemical and functional abnormalities that occur in Zellweger's syndrome.
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U2 - 10.1016/0952-3278(95)90001-2
DO - 10.1016/0952-3278(95)90001-2
M3 - Article
C2 - 7540307
AN - SCOPUS:0028883254
VL - 52
SP - 77
EP - 81
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
SN - 0952-3278
IS - 2-3
ER -