Characterization and physiological function of rat renal gamma-glutamyltranspeptidase.
Rat renal gamma-glutamyltranspeptidase is an intrinsic membrane glycoprotein. The larger of its two subunits is apparently folded into two distinguishable domains which are separated by a protease-sensitive sequence of amino acids. Membrane binding of gamma-glutamyltranspeptidase results from the hydrophobic interaction of the nonpolar domain of the amphipathic subunit with the lipid bilayer. Localization of at least a portion of the gamma-glutamyl binding site on the smaller subunit limits the active site of the enzyme to one side of the membrane. Within the kidney, the enzyme is primarily associated with the luminal surface of the brush border membrane of the proximal straight tubule. Comparison of the kinetic properties of gamma-glutamyltranspeptidase with the pH and the substrates available within the tubular fluid suggests that the physiologically significant reaction catalyzed by the transpeptidase is the hydrolysis of glutathione and its S-derivatives. The glutathionemia and glutathionuria observed in a patient who lacks detectable gamma-glutamyltranspeptidase activity and in mice following specific inhibition of transpeptidase, support the hypothesis that the enzyme plays a major role in glutathione catabolism. It now appears that the activities attributed to the gamma-glutamyl cycle do not participate in amino acid transport, but instead constitute three separate metabolic pathways; the intracellular synthesis of glutathione, the intracellular degradation of gamma-glutamyl peptides and the extracellular hydrolysis of glutathione. The finding that various cells release reduced and oxidized glutathione indicates that glutathione turnover may be a process of intracellular synthesis, excretion and extracellular degradation.
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000648:ultrastructure; D007700:Kinetics; D008565:Membrane Proteins; D008871:Microvilli / Q000201:enzymology; D051381:Rats; D013379:Substrate Specificity; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D008565:Membrane Proteins; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D000111:Acetylcysteine