Question

Is it possible forming pyroglutamic acid from glutamic acid in free solution? (have you any reference?)

Yes, glutamic acid can form pyroglutamic acid (2-pyrrolindone-5-carboxylic acid) in solution. This reaction links the amine group on the amino acid with the terminal carboxylic acid carbon through an amide bond. The reaction is enhanced at low pH and elevated temperatures. The reaction is reversible, and pyroglutamic acid can be converted to glutamic acid by acid hydrolysis. The chemistry of this system was first described some time ago: Wilson H. and R. K. Cannan (1937) The glutamic acid-pyrrolidone carboxylic acid system. J. Biol. Chem. Vol.119, 309-331. Yeast extract, which is commonly used for nutrients in studies of bacteria in culture, contains a relatively large amount of glutamic acid. Recent work has demonstrated that pyroglutamic acid, which forms spontaneously from glutamic acid, can inhibit the growth of some bacteria. This is especially important to note for studies of thermophilic bacteria, where the warm temperatures required for growth speed up the formation of pyroglutamic acid in the culture media: Park C.B., S. B. Lee and D.D.Y Ryu (2001) L-Pyroglutamate spontaneously formed from L-glutamate inhibits growth of the hyperthermophilic archaeon Sulfolobus solfataricus. Applied and Envrionmental Microbiol. Vol. 67, 3650-3654. There are many studies of pyroglutamic acid formation during metabolism. In humans, it is monitored for medical purposes, especially in cases of digestive or metabolic disorders. It also causes poor flavors in wine. Prof. Katherine H. Freeman (Penn State Astrobiology Research Center)
February 15, 2002