Studies on the α Oxidation of Phytanic Acid by Rat Liver Mitochondria

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is oxidized to CO2 in rat liver whole cell homogenates or washed mitochondria supplemented with ATP, NAD+, and NADPH. In the course of this degradation, α-hydroxyphytanic, pristanic, Δ2-pristenic, and 4,8,12-trimethyltridecanoic acids are formed as intermediates; they have been identified by gas-liquid chromatography or mass spectrometry. The proposed mechanism of mammalian catabolism of phytanic acid involves initial α oxidation leading through α-hydroxyphytanic acid to pristanic acid, and subsequent β oxidations. The α-oxidative process requires NADPH and O2, and the addition of Fe+++ ions greatly stimulates this reaction. Fe++ and a number of other heavy metal ions, as well as dipyridyl, lipoic acid, CoA—SH, and H2O2 generated in situ strongly inhibit it, whereas ascorbic acid, imidazole, aminopterin, and folic acid have little or no effect. The properties of the mammalian phytanic acid-α-oxidizing enzyme are discussed and compared with those of straight chain fatty acid-α-oxidizing systems in plants and animals.