Inhibition of 5-oxoprolinase by 2-imidazolidone-4-carboxylic acid.

Article Details

Citation

Copy to clipboard

Van der Werf P, Stephani RA, Orlowski M, Meister A

Inhibition of 5-oxoprolinase by 2-imidazolidone-4-carboxylic acid.

Proc Natl Acad Sci U S A. 1973 Mar;70(3):759-61.

PubMed ID

4514988 [ View in PubMed

]

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-[(14)C]proline to (14)CO(2) by rat-kidney slices but had no effect on the metabolism of [(14)C]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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	5-oxoprolinase	Protein	Humans	Unknown	Not Available	Details