Stereochemistry of pipecolic acid found in the urine and plasma of subjects with peroxisomal deficiencies.

Recently it was found that normal adults excrete pipecolic acid primarily as the D-enantiomer even though it is present in the blood stream mainly as the L-enantiomer (i.e. > 98% L). This study of pipecolic acid stereochemistry was extended to subjects with peroxisomal deficiencies since they are known to have high levels of pipecolic acid in their physiological fluids. Also, pipecolic acid stereochemistry was examined in young normal subjects since this group was not considered previously. It was found that the stereochemical composition of pipecolic acid in plasma was very similar for all subjects tested (i.e. > 98% of the L-enantiomer). However, the stereochemical composition of excreted pipecolic varied considerably. Urine samples from subjects with the most severe peroxisomal deficiency, i.e. cerebralhepatorenyl (Zellweger) syndrome (CHRS) contained little D-pipecolic acid. In fact the enantiomeric ratios for pipecolic acid in the urine and plasma of these subjects were very similar. This was not the case for normal subjects. Levels of D-pipecolic acid in the urine of subjects with 'less severe' peroxisomal deficiencies tended to be somewhat higher but they did not approach the levels found in normal adults. Several possible reasons for these results are discussed.