The occurrence of free L-pyrrolidone carboxylic acid in body fluids and tissues

Abstract

Received 9 May 1973 1. Introduction Pyrrolidone carboxylic acid (PCA) has been known as a cyclic derivative of glutamic acid for more than 90 years [ 11. An enzyme designated y-glutamyl cyclo- transferase (y-glutamyl lactamase) was found in mam- malian tissues [2] that catalyzes the conversion of L- y-glutamyl amino acids to L-PCA and free amino acids. This reaction represents probably the main route of formation of L-PCA in mammals [3,4]. L-PCA was found at the N-terminus of a number of peptides and proteins (for a review see [5]), and this compound was also postulated to be an intermediate of the y-glu- tamyl cycle, which was proposed as a transport system for amino acids [6]. Although these considerations in- dicate that L-PCA is an active metabolite, there are no reports demonstrating its presence as a normal constit- uent of body fluids and tissues. Indeed screening meth- ods in which gas chromatographic procedures were used for the determination of PCA as the methyl ester, failed to detect this compound in normal body fluids 171. We report the finding of siginificant amounts of PCA in tissues and body fluids by the application of a gas liquid chromatographic procedure, utilizing elec- tron capture detection. Analysis of the optical config- uration of glutamate derived by acid hydrolysis from PCA has shown that all of the PCA present in the cerebrospinal fluid is of the L-configuration and that a substantial fraction of the PCA in urine has the D- configuration.