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. 1973 Mar;70(3):759–761. doi: 10.1073/pnas.70.3.759

Inhibition of 5-Oxoprolinase by 2-Imidazolidone-4-Carboxylic Acid

Paul Van Der Werf 1, Ralph A Stephani 1, Marian Orlowski 1, Alton Meister 1
PMCID: PMC433352  PMID: 4514988

Abstract

L-2-Imidazolidone-4-carboxylic acid is an effective competitive inhibitor of the reaction catalyzed by 5-oxoprolinase, in which 5-oxo-L-proline (L-pyroglutamic acid, L-2-pyrrolidone-5-carboxylic acid, L-5-oxopyrrolidine-2-carboxylic acid) is converted to L-glutamate, with concomitant cleavage of ATP to ADP and orthophosphate. L-2-Imidazolidone-4-carboxylate decreased the rate of metabolism of 5-oxo-L-[14C]proline to 14CO2 by rat-kidney slices but had no effect on the metabolism of [14C]glutamate. Mice injected with L-2-imidazolidone-4-carboxylate exhibited greatly reduced ability to metabolize 5-oxo-L-proline, but metabolized glutamate at an essentially normal rate. The findings provide an approach to an animal model for the human condition 5-oxoprolinuria, in which there is apparently a deficiency of renal 5-oxoprolinase activity. The evidence indicates that 5-oxoproline is a normal metabolite.

Keywords: pyroglutamate, pyrrolidone carboxylate, glutathione, γ-glutamyl cycle, kidney, aminoacid transport

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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