Pyroglutamic Acid. Non-metabolic Formation, Function in Proteins and Peptides, and Characteristics of the Enzymes Effecting Its Removal

The formation of pyrrolidone carboxylic acid (PCA, pGlu) during protein biosynthesis is discussed. Studies are summarized which demonstrate that PCA is formed during the later stages of biosynthesis at the terminal phases of translation or as a post-translational event, just prior to cellular secretion of protein with amino-terminal PCA. Of the studies cited, the most convincing evidence suggests that PCA is derived from glutamine. Enzymes which selectivity remove PCA from the N-terminus, and of benefit in amino-acid sequence analysis, have been isolated and shown to have a ubiquitous distribution in various animal and plant cells. The investigations which lead to the isolation o these enzymes and the procedures for their use in removing amino-terminal PCA from proteins, are described. Finally, the biologic function of PCA and the effects of its chemical modification are discussed using the neuropeptide. Thyrotropin Releasing Factor (TRF) as a specific example.