PHYTANIC ACID ALPHA-OXIDATION - DECARBOXYLATION OF 2-HYDROXYPHYTANOYL-COA TO PRISTANIC ACID IN HUMAN LIVER

The degradation of the first intermediate in the alpha-oxidation of ph ytanic acid, 2-hydroxyphytanoyl-CoA, was investigated. Human liver hom ogenates rt ere incubated with 2-hydroxyphytanoyl-CoA or 2-hydroxyphyt anic acid, after which formation of 2-ketophytanic acid and pristanic acid were studied. 2-Hydroxyphytanic acid it as converted into 2-ketop hytanic acid and pristanic acid. When ATP, Mg2+, and coenzyme A were a dded to the incubation medium, higher amounts of pristanic acid were f ormed, whereas the formation of 2-ketophytanic acid strongly decreased . When 2-hydroxyphytanoyl-CoA was used as substrate, there was virtual ly no 2-ketophytanic acid formation. However, pristanic acid was forme d in higher amounts than with 2-hydroxyphytanic acid as substrate. Thi s reaction nas stimulated by NAD(+) and NADP(+). Pristanic acid, and n ot pristanoyl-CoA was found to he the product of the reaction. These r esults suggest tile existence of two pathways for decarboxylation of 2 -hydroxyphytanic acid. The first one: starting from 2-hydroxyphytanic acid, involves the formation of 2-ketophytanic acid with only a small amount of pristanic acid being formed. The second pathway, which start s from 2-hydroxyphytanoyl-CoA, does not involve 2-ketophytanic acid an d generates higher amounts of pristanic acid. The first pathway, which is peroxisomally localized, was found to be deficient in Zellweger sy ndrome, whereas the second pathway, localized in microsomes, was norma lly active. We conclude that the second pathway is predominant under i n vitro conditions.