A MAJOR PATHWAY FOR MAMMALIAN OXIDATIVE DEGRADATION OF PHYTANIC ACID

A series of branched-chain saturated fatty acids accumulated in tissues of weanling mice fed regular chow supplemented with 2% phytanic acid (3,7,11,15 tetramethylhexadecanoic acid). They were identified by combined gas-liquid chromatography-mass spectrometry as phytanic acid, α-hydroxyphytanic acid, and the 19-, 16- and 14-carbon homologs of phytanic acid. Trace quantities of the 9-carbon homolog have also been detected by gas-liquid chromatography. When the regular chow is supplemented with 2% phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol),Δ2-phytenic acid accumulated in liver in addition to the compounds listed above. No evidence was found for the presence of α-ketophytanic acid, or of 15- and 17-carbon intermediates. The latter two would be expected if carbon dioxide fixation to the branch-methyl group were required in phytol or phytanate metabolism, as in the bacterial metabolism of farnesoic acid. Dietary supplementation with 3,7,11-trime thyldodecanoic acid produces accumulation in liver of the fed compound only. Intravenous injection of uniformly 14C-labeled phytanic acid in mice led to significant incorporation of radioactivity associated on gas-liquid chromatography with 19-16-, 14- and 11-carbon isoprenoid acids. Rat liver in vivo also rapidly converted in high yield uniformly 14C-labeled phytanic acid or 2,3-dideuterophytanic acid to uniformly 14C-labeled pristanic acid and 2-deuteropristanic acid, respectively. The oxidation of uniformly 14C-labeled phytanic acid to 14CO2 was not impaired in biotindeficient rats. The proposed main metabolic pathway of phytanic acid in mammals consists of an α-oxidative process leading through α-hydroxyphytanic acid to pristanic acid, followed by a series of β-oxidative steps. The chemical syntheses of a number of isoprenoid acids are described. © 1969.