CONVERSION OF EICOSAPENTAENOIC ACID TO CHAIN-SHORTENED OMEGA-3-FATTY-ACID METABOLITES BY PEROXISOMAL OXIDATION

Human skin fibroblasts can convert arachidonic acid to 14- and 16-carb on polyunsaturated fatty acid products by peroxisomal beta-oxidation. The purpose of this study was to determine whether similar products ar e formed from eicosapentaenoic acid (EPA) and whether EPA and arachido nic acid compete for utilization by this oxidative pathway. Three radi olabeled metabolites with shorter retention times than EPA on reverse- phase high-performance liquid chromatography accumulated in the medium during incubation of fibroblasts with [5,6,8,9,11,12,14,15,17,18-H-3] EPA ([H-3]EPA). These metabolites, which were not formed from [1-C-14 ]EPA and were not detected in the cells, were identified as tetradecat rienoic acid (14:3n-3), hexadecatetraenoic acid (16:4n-3), and octadec atetraenoic acid (18:4n-3), The most abundant product under all of the conditions tested was 16:4n-3, [H-3]EPA was converted to 16:4n-3 and 14:3n-3 by fibroblasts deficient in mitochondrial long-chain acyl CoA dehydrogenase, but not by Zellweger syndrome or acyl CoA oxidase mutan ts that are deficient in peroxisomal beta-oxidation, Competition studi es indicated that 16:4n-3 formation from 5 mu M [H-3]EPA was reduced b y 60% when 10 mu M arachidonic acid was added, but the conversion of [ H-3]arachidonic acid to its chain-shortened products was not decreased by the addition of 10 mu M EPA.ir These findings demonstrate that as in the case of arachidonic acid, chain-shortened polyunsaturated fatty acid products accumulate when EPA undergoes peroxisomal beta-oxidatio n, While EPA does not reduce arachidonic acid utilization by this path way, it is possible that some biological actions of EPA may be mediate d by the formation of the corresponding EPA products, 16:4n-3 and 14:3 n-3.