Azetidine-2-carboxylic acid contaminated dietary proline as a cause of urinary excretion of 4-amino-2-(S-cysteinyl)butyric acid in patients on oral treatment with a synthetic diet.

Three children with branched-chain ketoaciduria (maple syrup urine disease) were found to excrete an abnormal amino acid when they were on an artificial diet. This substance was identified as 4-amino-2-(S-cysteinyl)butyric acid with the use of column liquid chromatography, gas chromatography--mass spectrometry of various derivatives, and 360 MHz 1H-NMR spectroscopy. The same compound was detected in urine samples from subjects undergoing an oral loading test with L-proline. The chromatographic analysis of commercial proline from two sources indicated that one of the batches was contaminated (less than 1%) with L-azetidine-2-carboxylic acid (the homologue of proline with a four-membered ring). The latter compound is probably metabolized by the human via ring-opening and addition of a cysteine moiety. It is highly probable that the artificial diet given to the patients contained the impure proline and that the L-azetidine-2-carboxylic acid in the proline gave rise to the excretion of the 4-amino-2-(S-cysteinyl)butyric acid.