Localization of pipecolic acid metabolism in rat liver peroxisomes: probable explanation for hyperpipecolataemia in Zellweger syndrome.

The metabolism of [14C]pipecolic acid was studied in peroxisomal fractions of rat liver obtained by density gradient centrifugation in Percoll. The production rate of [14CO2] was used to measure the metabolic activity of the fractions towards [14C]carboxypipecolic acid as a substrate. It was shown that this activity was located in the peroxisomal fractions by comparison with the peroxisomal marker enzyme urate oxidase (EC 1.7.3.3). The process was markedly elevated by the addition of FAD. The apparent Km for DL-pipecolic acid was found to be 1.2 mmol L-1. Addition of ATP (1 mmol L-1) did not influence the decarboxylation rate of pipecolic acid. These results might explain the defective metabolism of pipecolic acid in patients with Zellweger syndrome who are lacking peroxisomes.