PEROXISOMAL BETA-OXIDATION OF POLYUNSATURATED LONG-CHAIN FATTY-ACIDS IN HUMAN FIBROBLASTS - THE POLYUNSATURATED AND THE SATURATED LONG-CHAIN FATTY-ACIDS ARE RETROCONVERTED BY THE SAME ACYL-COA OXIDASE

The metabolism of the C22 unsaturated fatty acids erucic acid (22:1(n- 9)), adrenic acid (22:4(n-6)), docosapentaenoic acid (22:5(n-3)) and d ocosahexaenoic acid (22:6(n-3)) was studied in cultured fibroblasts fr om patients with acyl-CoA oxidase deficiency, the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. [3-C-14] 22 :4 (n-6) and [3-C-14] 22:5 (n-3) were shortened (retroconverted) to [1 -C-14] 20:4 (n-6) and [1-C-14] 20:5 (n-3), respectively, in normal and X-ALD fibroblasts. In Zellweger and acyl-CoA oxidase deficient fibrob lasts these reactions were deficient. Since the retroconversion is nor mal in X-ALD fibroblasts peroxisomal very long chain (lignoceryl) CoA ligase is probably not required for the activation of C22 unsaturated fatty acids. The present work with fibroblasts from patients with a sp ecific acyl-CoA oxidase deficiency, previously shown to have a deficie nt peroxisomal clofibrate-inducible acyl-CoA oxidase, and which accumu late 24:0 and 26:0 fatty acids, supports the view that this enzyme is responsible for the chain-shortening of docosahexaenoic acid (22:6(n-3 )), erucic acid (22:1(n-9)), docosapentaenoic acid (22:5(n-3)), and ad renic acid (22:4(n-6)) as well.