Peroxisomal oxidation of pipecolic acid in the rat

Postnuclear fractions from rat liver and kidney oxidize L-pipecolic acid, a by-product of lysine catabolism, in a hydrogen peroxide-producing reaction. This pipecolate oxidase2) activity is enhanced in preparations from animals treated with clofibrate and thyroxine, substances known to act as peroxisome proliferators and inducers of the peroxisomal fatty acid beta-oxidation. The enzymatic activity co-purified with the peroxisomal marker fatty acyl-CoA oxidase2) rather than with the mitochondrial marker glycerol-3-phosphate dehydrogenase2). Thus the degradation of L-pipecolic acid may start in the rat with a peroxisomal oxidase comparable to other hydrogen peroxide-producing oxidases found in peroxisomes. These findings provide indirect evidence that the marked hyperpipecolinaemia described in a group of human genetic disorders connected with peroxisomal defects such as Zellweger syndrome might be due to the absence of peroxisomal L-pipecolate oxidase.