Identification of Pristanal Dehydrogenase Activity in Peroxisomes: Conclusive Evidence That the Complete Phytanic Acid α-Oxidation Pathway Is Localized in Peroxisomes

• DOI: 10.1006/bbrc.2001.4835
• Publication Date: 2002-09-16T13:50:03Z
• Authors: G.A. Jansen; D.M. van den Brink; R. Ofman; O. Draghici; G. Dacremont; R.J.A. Wanders
• Keywords: Male; Aldehydes; 0303 health sciences; Fatty Acids; Fibroblasts; In Vitro Techniques; Aldehyde Oxidoreductases; Rats; Phytanic Acid; Sjogren-Larsson Syndrome; 03 medical and health sciences; Liver; Peroxisomes; Animals; Humans; Refsum Disease; Rats, Wistar; Oxidation-Reduction

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which, due to the methyl-group at the 3-position, can not undergo beta-oxidation unless the terminal carboxyl-group is removed by alpha-oxidation. The structure of the phytanic acid alpha-oxidation machinery in terms of the reactions involved, has been resolved in recent years and includes a series of four reactions: (1) activation of phytanic acid to phytanoyl-CoA, (2) hydroxylation of phytanoyl-CoA to 2-hydroxyphytanoyl-CoA, (3) cleavage of 2-hydroxyphytanoyl-CoA to pristanal and formyl-CoA, and (4) oxidation of pristanal to pristanic acid. The subcellular localization of the enzymes involved has remained enigmatic, with the exception of phytanoyl-CoA hydroxylase and 2-hydroxyphytanoyl-CoA lyase which are both localized in peroxisomes. The oxidation of pristanal to pristanic acid has been claimed to be catalysed by the microsomal aldehyde dehydrogenase FALDH encoded by the ALDH10-gene. Making use of mutant fibroblasts deficient in FALDH activity, we show that phytanic acid alpha-oxidation is completely normal in these cells. Furthermore, we show that pristanal dehydrogenase activity is not fully deficient in FALDH-deficient cells, implying the existence of one or more additional aldehyde dehydrogenases reacting with pristanal. Using subcellular localization studies, we now show that peroxisomes contain pristanal dehydrogenase activity which leads us to conclude that the complete phytanic acid alpha-oxidation pathway is localized in peroxisomes.