Conversion of arachidonic acid to tetradecadienoic acid by peroxisomal oxidation.
Human skin fibroblasts convert [5,6,8,9,11,12,14,15-3H]arachidonic acid to two radiolabeled polar metabolites that accumulate in the culture medium. Previous studies identified the most abundant of these products as 4,7,10-hexadecatrienoic acid (16:3). We have now identified the second metabolite as 5,8-tetradecadienoic acid (14:2). Fibroblasts deficient in mitochondrial long-chain acyl coenzyme A dehydrogenase produce increased amounts of 14:2 from arachidonic acid. By contrast, Zellweger fibroblasts which are deficient in peroxisomal beta-oxidation do not convert arachidonic acid to either 14:2 or 16:3. These results demonstrate that 14:2 can be synthesized from arachidonic acid, that this oxidative process occurs in the peroxisomes, and that the pathway does not function in Zellweger's syndrome and similar diseases where there is a genetic deficiency in peroxisomal beta-oxidation.
Spector
A A
AA
Department of Biochemistry, University of Iowa, Iowa City 52242, USA.
Williard
D E
DE
Kaduce
T L
TL
Gordon
J A
JA
D044942:Acyl-CoA Dehydrogenase, Long-Chain; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D044943:Fatty Acid Desaturases / Q000172:deficiency; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D012867:Skin; D015211:Zellweger Syndrome / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; C108157:5,8-tetradecadienoic acid; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases; D044942:Acyl-CoA Dehydrogenase, Long-Chain