标题:Accumulation of 5-Oxoproline in Mouse Tissues After Inhibition of 5-Oxoprolinase and Administration of Amino Acids: Evidence for Function of the γ-Glutamyl Cycle
期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1974
卷号:71
期号:4
页码:1026-1029
DOI:10.1073/pnas.71.4.1026
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要: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.
关键词:pyroglutamate ; pyrrolidone carboxylate ; glutathione ; amino-acid transport