Two genetic deficiencies of the [gamma]-glutamyl cycle, glutathione synthetase deficiency and 5-oxoprolinase deficiency (3), lead to very large increases in 5-oxoproline excretion.
Finally, a previous investigation of another subject with acute onset 5-oxoprolinuria yielded normal activities of glutathione synthetase and 5-oxoprolinase (1).
However, it is possible that, under the altered conditions resulting from acetaminophen ingestion, glutathione synthetase becomes rate limiting or is inhibited, leading to the accumulation of [gamma]-glutamyl cysteine, which can then be acted on by [gamma]-glutamyl cyclotransferase to produce L-5-oxoproline (Fig.
An inherited defect in the enzyme glutathione synthetase was first described in a 19-year-old man in 1970 .
The only main abnormality evident in affected individuals is increased concentrations of 5-oxoproline, which are not so great as those found in cases of glutathione synthetase deficiency and characteristically do not result in major metabolic acidosis.