The deficient degradation of synthetic 2- and 3-methyl-branched fatty acids in fibroblasts from patients with peroxisomal disorders.
The oxidation of pristanic and phytanic acids by human skin fibroblasts was compared to that of their synthetic analogues, 2-methylpalmitic and 3-methylmargaric acids. The synthetic compounds and natural substrates were degraded at comparable rates in control and X-linked adrenoleukodystrophy fibroblasts. The alpha-decarboxylation of 3-methylmargaric acid, similarly to that of phytanic acid, was affected in Refsum disease and Zellweger syndrome, but not in X-linked adrenoleukodystrophy. The beta-oxidation of 2-methylpalmitic acid, similarly to that of pristanic acid, was deficient in fibroblasts derived from patients suffering 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. The 1-14C-labelled 2- and 3-methyl-branched fatty acids, which are easier to synthesize that the natural analogues, are therefore valuable tools for the diagnosis of human peroxisomal disorders.
Van Veldhoven
P P
PP
Katolieke Universiteit Leuven, Afdeling Farmakologie, Belgium.
Huang
S
S
Eyssen
H J
HJ
Mannaerts
G P
GP
D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D010831:Phytanic Acid / Q000378:metabolism; D012035:Refsum Disease / Q000378:metabolism*; D014960:X Chromosome; D015211:Zellweger Syndrome / Q000378:metabolism*
D005227:Fatty Acids; D010168:Palmitates; D010831:Phytanic Acid; C033637:3-methylheptadecanoic acid; C002844:pristanic acid; C019012:methyl palmitate