Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid.
In the present paper, we describe the current state of knowledge regarding the enzymology of the phytanic acid alpha-oxidation pathway. The product of phytanic acid alpha-oxidation, i.e. pristanic acid, undergoes three cycles of beta-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 omega-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 alpha-oxidation system.
Wanders
R J A
RJ
Genetic Metabolic Diseases Laboratory, Room F0-224, Departments of Clinical Chemistry and Pediatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. r.j.wanders@amc.uva.nl
Komen
J C
JC
D001692:Biological Transport; D006801:Humans; D006868:Hydrolysis; D006900:Hydroxylation; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D010831:Phytanic Acid / Q000378:metabolism*; D012035:Refsum Disease / Q000378:metabolism*
D010831:Phytanic Acid