Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants

Abstract

Urinary 5-L-oxoproline was measured in term and preterm infants from shortly after birth until 6 weeks of postnatal age to determine their ability to synthesise glycine. In term infants the excretion was five to 10 times that seen in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a significant inverse linear correlation between the excretion of 5-L-oxoproline and length of gestation or birthweight. By 6 weeks of age there was no longer a significant difference in 5-L-oxoproline between term and preterm infants. There was no difference in the excretion of 5-L-oxoproline between boys and girls, or between infants fed on human milk or an artificial formula. If, in part, variability in the excretion of 5-L-oxoproline is determined by the extent to which the endogenous formation of glycine is adequate, then glycine formation may be marginal during early life, more so in preterm than in term infants, providing additional evidence that glycine is a conditionally essential amino acid in the neonate.

Figure 1

Glutathione, γ-glutamylcysteinlglycine is synthesised in two stages catalysed by glutamate-cysteine ligase ( γ-glutamylcysteine synthetase) (EC 6.3.2.2), and glutathione synthase (EC 6.3.2.3). Glutathione inhibits feedback on γ-glutamylcysteinlglycine synthase, so that in the congenital absence of glutathione glutamate excess γ-glutamylcysteinlglycine is cleaved by , γ-glutamyl cyclotransferase (EC 2.3.2.4) to give 5-L-oxoproline, which can be converted to glutamic acid by 5-L-oxoprolinase. Increased urinary 5-L-oxoproline is also produced when the availability of glycine, the substrate for glutathione synthetase, is limited.

Figure 2

The excretion of 5-L-oxoproline/creatinine was measured in the urine of newborn infants within 72 hours of birth. There was a close correlation between birthweight and gestational age, and both showed a strong correlation with the excretion of 5-L-oxoproline (birthweight = 245−[40 ×5-L-oxoproline]; r =−0.46, P = 0.0001: gestational age = 458 −[9×5-L-oxoproline]; r= 0.5, P = 0.00002).

Figure 3

The excretion of 5-L-oxoproline/creatinine was measured in the urine of term infants (open bars) and preterm infants (shaded bars) within 72 hours of birth. and at intervals up to 6 weeks of age. Values shown are mean (SE). with significant differences: *P < 0.05; *** P < 0.01 for preterms compared with terms of the same age and P < 0.05; P < 0.01 when compared with excretion of 5-L-oxoproline within 72 hours of birth.