Urinary Excretion of 5-L-Oxoproline (Pyroglutamic Acid) Is Increased during Recovery from Severe Childhood Malnutrition and Responds to Supplemental Glycine

We hypothesized that a limitation in the endogenous formation of glycine might constrain catch-up growth during recovery from severe childhood malnutrition. The urinary excretion of 5-L-oxoproline is increased when the glycine available for glutathione synthesis is limited. Urinary excretion of 5-L-oxoproline was measured throughout recovery in 12 children (aged 16 +/- 6 mo) with severe malnutrition. Urinary 5-L-oxoproline was similar at admission and after recovery, but was increased significantly during rapid catch-up growth. There was a significant relationship between the rate of weight gain and 5-L-oxoproline excretion in urine. In nine children (aged 15 +/- 5 mo), the effect of oral supplementation with glycine, [1.7 mmol/(kg x d) for 48 h] during rapid catch-up growth on 5-L-oxoprolinuria and blood glutathione concentration was determined. In seven of the nine children weight gain was less than 17 g/(kg x d) and following oral glycine supplements 5-L-oxoproline excretion was reduced up to 64% and blood glutathione concentration increased up to 100%. In the two children who were gaining weight at a rate > 17 g/(kg x d), glycine supplementation was associated with a further increase in 5-L-oxoproline excretion and a decrease in blood glutathione. If 5-L-oxoproline is an index of the relative availability of glycine, then the data indicate that glycine may be limiting during rapid catch-up growth. This would have important implications for repletion of muscle and gain in height.