Peroxisomes, Refsum's disease and the α- and ω-oxidation of phytanic acid

Abstract

In the present paper, we describe the current state of knowledge regarding the enzymology of the phytanic acid α-oxidation pathway. The product of phytanic acid α-oxidation, i.e. pristanic acid, undergoes three cycles of β-oxidation in peroxisomes after which the products, including 4,8-dimethylnonanoyl-CoA, propionyl-CoA and acetyl-CoA, are exported from the peroxisome via one of two routes, including (i) the carnitine-dependent route, mediated by CRAT (carnitine acetyltransferase) and CROT (carnitine O-octanoyltransferase), and (ii) the free acid route, mediated by one or more of the peroxisomal ACOTs (acyl-CoA thioesterases). We also describe our recent data on the ω-oxidation of phytanic acid, especially since pharmacological up-regulation of this pathway may form the basis of a new treatment strategy for ARD (adult Refsum's disease). In patients suffering from ARD, phytanic acid accumulates in tissues and body fluids due to a defect in the α-oxidation system.