THE DEFICIENT DEGRADATION OF SYNTHETIC 2-METHYL-BRANCHED AND 3-METHYL-BRANCHED FATTY-ACIDS IN FIBROBLASTS FROM PATIENTS WITH PEROXISOMAL DISORDERS

The oxidation of pristanic and phytanic acids by human skin fibroblast s was compared to that of their synthetic analogues, 2-methylpalmitic and 3-methylmargaric acids. The synthetic compounds and natural substr ates were degraded at comparable rates in control and X-linked adrenol eukodystrophy fibroblasts. The alpha-decarboxylation of 3-methylmargar ic acid, similarly to that of phytanic acid, was affected in Refsum di sease and Zellweger syndrome, but not in X-linked adrenoleukodystrophy . The beta-oxidation of 2-methylpalmitic acid, similarly to that of pr istanic acid, was deficient in fibroblasts derived from patients suffe ring from Zellweger syndrome, confirming the importance of peroxisomes in the breakdown of 2-methyl-branched fatty acids. No deficiency was observed in fibroblasts from X-linked adrenoleukodystrophy patients. T he 1-C-14-labelled 2- and 3-methyl-branched fatty acids, which are eas ier to synthesize that the natural analogues, are therefore valuable t ools for the diagnosis of human peroxisomal disorders.