PHYTANIC ACID ALPHA-OXIDATION IN RAT-LIVER MITOCHONDRIA

The alpha-oxidation of phytanic acid in rat liver is a mitochondrial f unction. The inhibition of phytanic acid oxidation activity by inhibit ors of acyl-CoA ligases (Naproxen and Triacsin C) and that of carnitin e acyltransferase I (2-(5-(4-chlorophenyl)pentyl)oxirane-2 carboxylic acid (POCPA) and 2-bromopalmitate) and increase in phytanic acid oxida tion activity by the addition of exogenous carnitine and CoA to purifi ed mitochondria suggests that phytanoyl-CoA ligase and carnitine acylt ransferase I are essential for the activation and transport of phytani c acid across the mitochondrial membrane. This was further supported b y the fact that activation of phytanic acid to phytanoyl-CoA was requi red only in intact mitochondria but not in mitochondria permealized wi th digitonin. DesulfoCoA, Naproxen and POCA treatment resulted in a si gnificant decrease in phytanic acid oxidation in intact mitochondria b ut not in digitonin permealized mitochondria. These results show that alpha-oxidation of phytanic acid to pristanic acid, in contrast to bet a-oxidation of fatty acids, requires free fatty acid as substrate. The inhibition of alpha-oxidation (similar to 90%) of phytanic acid by di fferent cytochrome P-450 enzyme inhibitors indicated that alpha-oxidat ion of phytanic acid is mediated through cytochrome P-450 containing e nzyme system. Similar to the omega-hydroxylation system in endoplasmic reticulum, alpha-hydroxylation and the subsequent cr-oxidation of phy tanic acid in mitochondria is induced by ciprofibrate, a hypolipidemic drug.