2-HYDROXYPHYTANIC ACID OXIDASE ACTIVITY IN RAT AND HUMAN LIVER AND ITS DEFICIENCY IN THE ZELLWEGER-SYNDROME

Phytanic acid is a saturated, branched-chain fatty acid which as a con sequence of the presence of a methyl group at the 3-position cannot be degraded by beta-oxidation. Instead, phytanic acid first undergoes al pha-oxidation to yield pristanic acid which can be degraded by beta-ox idation. The structure of the cr-oxidation pathway and its subcellular localization has remained an enigma although there is convincing evid ence that 2-hydroxyphytanic acid is an obligatory intermediate. We hav e now studied the degradation of 2-hydroxyphytanic acid in both rat an d human liver. The results show that 2-hydroxyphytanic acid is convert ed to 2-ketophytanic acid in homogenates of rat as well as human liver . Detailed studies in rat liver showed that the enzyme involved is loc alized in peroxisomes accepting molecular oxygen as second substrate a nd producing H2O2. 2-Ketophytanic acid formation from 2-hydroxyphytani c acid was found to be strongly deficient in liver samples from Zellwe ger patients which lack morphologically distinguishable peroxisomes. T he latter results not only provide an explanation for the elevated lev els of 2-hydroxyphytanic acid in Zellweger patients but also suggest t hat the subcellular localization of 2-hydroxyphytanic acid dehydrogena tion is identical in rat and man, i.e., in peroxisomes.