THE ZELLWEGER SYNDROME - DEFICIENT CONVERSION OF DOCOSAHEXAENOIC ACID (22-6(N - 3)) TO EICOSAPENTAENOIC ACID (20-5(N - 3)) AND NORMAL DELTA-4-DESATURASE ACTIVITY IN CULTURED SKIN FIBROBLASTS

The metabolism of docosahexaenoic acid (22:6(n-3))and adrenic acid (22:4(n-6)) was studied in cultured fibroblasts from patients with the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. It was shown that [4,5-3H] 22:6(n-3) is retroconverted to labelled eicosapentaenoic acid (20:5(n-3)) in normal and X-ALD fibroblasts, while this conversion is deficient in Zellweger fibroblasts. [U-14C]Eicosapentaenoic acid (20:5(n-3)) is elongated to docosapentaenoic acid (22:5(n-3))in all three cell lines. With [U-14C]20:5(n-3) as the substrate, shorter fatty acids were not detected. With [4,5-3H]22:6(n-3) as the substrate, labelled fatty acids were esterified in the phospholipid- and triacylglycerol-fraction to approximately the same extent in all three cell lines. [2-14C]Adrenic acid (22:4(n-6)) was desaturated to 22:5(n-6) and elongated to 24:4(n-6) in all three cell lines and to the largest extent in the Zellweger fibroblasts. This agrees with the view that the Δ4-desaturase is not a peroxisomal enzyme. The observation that the retroconversion of 22:6(n-3) to 20:5(n-3) is deficient in Zellweger fibroblasts strongly suggest that the β-oxidation step in the retroconversion is a peroxisomal function. Peroxisomal very-long-chain (lignoceryl) CoA ligase is probably not required for the activation of 22:6(n-3), since the retroconversion to 20:5(n-3) is normal in X-ALD fibroblasts. © 1990.