L-gamma-(Threo-beta-methyl)glutamyl-L-alpha-aminobutyrate, a selective substrate of alpha-glutamyl cyclotransferase.
L-gamma(Threo-beta-methyl)glutamyl-L-alpha-aminobutyrate was was prepared and found to be an excellent substrate of gamma-glutamyl cyclotransferase; in contrast to gamma-glutamyl-glutamine and other good substrates of cyclotransferase, the new substrate is not acted upon by gamma-glutamyl transpeptidase. gamma-Glutamyl cyclotransferase converts the new substrate to alpha-aminobutyrate and 3-methyl-5-oxoproline; the latter compound is not a substrate of 5-oxoprolinase. These properties of L-gamma-(threo-beta-methyl)glutamyl-L-alpha-aminobutyrate facilitate its use in selectively determining cyclotransferase activity in biological materials that have transpeptidase activity. Thus, the new substrate was used here for the determination of the cyclotransferase activity of homogenates of various mouse tissues. The new substrate was also used to examine gamma-glutamyl cyclotransferase activity in vivo; thus, the rate of respiratory 14CO2 formation after administration of L-gamma-(threo-beta-methyl)glutamyl-L-alpha-amino[14C]butyrate to mice provides a valid measure of cyclotransferase activity. beta-Aminoglutaryl-L-alpha-aminobutyrate is a competitive inhibitor of cyclotransferase (apparent Ki, 0.6 mM). Administration of beta-amino-glutaryl-L-alpha-aminobutyrate to mice out only decreased the level of 5-oxoproline in the kidney of control mice, but also of mice in which kidney 5-oxoproline levels were increased by administration of methionine. Administration of beta-aminoglutaryl-L-alpha-aminobutyrate to mice decreased the in vivo metabolism of L-(threo-beta-methyl)glutamyl-L-alpha-amino[14C]butyrate as indicated by a marked decrease in the rate of respiratory 14CO2 formation. The findings indicate that gamma-glutamyl cyclo-transferase is a major in vivo catalyst for the formation of 5-oxoproline.
D000217:Acyltransferases / Q000378:metabolism*; D000613:Aminobutyrates; D000818:Animals; D001921:Brain / Q000201:enzymology; D004151:Dipeptides; D005971:Glutamates; D006909:Hydroxyproline / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D012867:Skin / Q000201:enzymology; D013737:Testis / Q000201:enzymology; D014018:Tissue Distribution; D005722:gamma-Glutamylcyclotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000613:Aminobutyrates; D004151:Dipeptides; D005971:Glutamates; C027535:beta-aminoglutaryl-L-alpha-aminobutyrate; C027534:L-gamma-(threo-beta-methyl)glutamyl-L-alpha-aminobutyrate; D000217:Acyltransferases; D005722:gamma-Glutamylcyclotransferase; D006909:Hydroxyproline