Formation of a novel arachidonic acid metabolite in peroxisomes.
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 mumol/L. The compound, identified as hexadecatrienoic acid, was not produced by Zellweger fibroblasts which are deficient in peroxisomal fatty acid beta-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 beta-oxidation. The absence of this pathway may account for some of the biochemical and functional abnormalities that occur in Zellweger's syndrome.
Gordon
J A
JA
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242, USA.
Heller
S K
SK
Rhead
W J
WJ
Watkins
P A
PA
Spector
A A
AA
D000326:Adrenoleukodystrophy / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D002806:Chondrodysplasia Punctata / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D012035:Refsum Disease / Q000378:metabolism; D013997:Time Factors; D015211:Zellweger Syndrome / Q000378:metabolism
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; C094145:4,7,10-hexadecatrienoic acid; D016718:Arachidonic Acid