Accumulation of 5-oxoproline in mouse tissues after inhibition of 5-oxoprolinase and administration of amino acids: evidence for function of the gamma-glutamyl cycle.
5-Oxoprolinase catalyzes the conversion of 5-oxo-L-proline (L-pyroglutamate, L-2-pyrrolidone-5-carboxylate) to L-glutamate with concomitant stoichiometric cleavage of ATP to ADP and inorganic orthophosphate. In this reaction, a step in the gamma-glutamyl cycle, 5-oxoproline (formed by the action of gamma-glutamylcyclotransferase on gamma-glutamyl amino acids, which are in turn formed by transpeptidation of amino acids with glutathione), is made available for glutathione synthesis. When mice are injected with L-2-imidazolidone-4-carboxylate, a competitive inhibitor of 5-oxoprolinase, they accumulate 5-oxoproline in their tissues (kidney, liver, brain, and eye) and excrete it in the urine. Mice given the inhibitor together with one of several L-amino acids accumulate and excrete much more 5-oxoproline than when they are given the inhibitor alone. Such augmentation of 5-oxoproline accumulation offers evidence for the function of the gamma-glutamyl cycle in vivo and supports the view that 5-oxoproline is a quantitatively significant metabolite.
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002264:Carboxylic Acids / Q000494:pharmacology; D005123:Eye / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011760:Pyrrolidinones / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000032:analysis / Q000378:metabolism / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000596:Amino Acids; D002264:Carboxylic Acids; D005971:Glutamates; D007093:Imidazoles; D011760:Pyrrolidinones; D005723:gamma-Glutamyltransferase; D000581:Amidohydrolases; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid