A novel mechanism for group translocation: substrate-product reutilization by gamma-glutamyl transpeptidase in peptide and amino acid transport.
Gamma-glutamyl transpeptidase (gamma-GTP) is suggested to act as a carrier in the group translocation of oligopeptides and possibly some amino acids across cellular membranes. It is proposed that the process may involve the repetitive transfer of gamma-glutamyl groups to acceptor peptides which are being translocated from the exterior of the cell to its interior. After group translocation of the peptides has occurred with concomitant formation of gamma-glutamyl peptide products, it is suggested that the products might then be utilized as substrate for the enzyme in order to permit the translocation of other peptides from the exterior. The system is economical and requires only that it be primed with an appropriate source of gamma-glutamyl peptides, such as glutathione. In contrast to most group translocation systems previously described, substrate-product reutilization by gamma-GTP would not be expected to accumulate peptides against a concentration gradient. Mechanisms for maintaining low intracellular concentrations of the translocated peptides are described. Studies on acceptor substrate specificity of gamma-GTP from bovine choroid plexus and rat kidney show some glycyl peptides are much better substrates than free amino acids in accord with the proposal that gamma-GTP might be primarily involved in peptide translocation. Both kinetic and topological evidence support the suggestion that repetitive transfer of gamma-glutamyl moieties by gamma-GTP could occur during group translocation of peptides and possibly some amino acids.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002831:Choroid Plexus / Q000201:enzymology; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008954:Models, Biological; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D000596:Amino Acids; D002352:Carrier Proteins; D009842:Oligopeptides; D005723:gamma-Glutamyltransferase; D005978:Glutathione