Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain
fatty acid derived from dietary sources and broken down in the peroxisome to
pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) via alpha-oxidation.
Pristanic acid then undergoes beta-oxidation in peroxisomes.
Phytanic acid naturally occurs as a mixture of (3S,7R,11R)- and (3R,7R,11R)-diastereomers. In contrast to the alpha-oxidation system, peroxisomal beta-oxidation is stereospecific and only accepts (2S)-isomers. Therefore, a
racemase called
alpha-methylacyl-CoA racemase is required to convert (2R)-pristanic
acid into its (2S)-isomer. To further investigate the stereochemistry of the peroxisomal oxidation systems and their substrates, we have developed a method using gas-liquid chromatography-mass spectrometry to analyze the isomers of phytanic, pristanic, and trimethylundecanoic
acid in plasma from patients with various peroxisomal
fatty acid oxidation defects. In this study, we show that in plasma of patients with a peroxisomal beta-oxidation deficiency, the relative amounts of the two diastereomers of
pristanic acid are almost equal, whereas in patients with a defect of
alpha-methylacyl-CoA racemase, (2R)-pristanic
acid is the predominant isomer. Furthermore, we show that in
alpha-methylacyl-CoA racemase deficiency, not only
pristanic acid accumulates, but also one of the metabolites of
pristanic acid, 2610-trimethylundecanoic
acid, providing direct in vivo evidence for the requirement of this
racemase for the complete degradation of
pristanic acid.