Effect of glycine supplementation on the pyroglutamic aciduria during recovery from severe malnutrition - abstract

ABSTRACT

We have previously demonstrated that as benzoic acid conjugates with endogenous glycine to form hippuric acid, the resulting glycine debt is associated with an increased pyroglutamic acid (PGA) excretion. We concluded that PGA could be used as an index of glycine insufficiency. Glycine is a substrate for glutathione (GSH) synthesis and PGA is an intermediate of the gamma-glutamyl cycle in which GSH is formed. As demand for glycine is enormous during periods of rapid growth, we supplemented glycine (127 mg/kg/d) to five rapid growing children (weight gain > 10g/kg/d) during recovery from severe malnutrition. Urinary PGA and blood GSH were measured before and after supplementation. SUBJECT 1 Diagnosis - kwashiorkor, Age - 18, Wt - 7.34, Change PGA - -73, Change GSH - +6.6; SUBJECT 2 Diagnosis - Mar/kwash, Age - 23, Wt - 6.55, Change PGA - -233, Change GSH - +7.6; SUBJECT 3 Diagnosis - mar/kwash, Age - 10, Wt 7.89, Change PGA - -55, Change GSH - +10.4; SUBJECT 4 Diagnosis - undernourished, Age - 14, Wt - 7.93, Change PGA - -53, Change GSH - +8.2; SUBJECT 5 Diagnosis - marasmus, Age - 12, Wt - 6.39, Change PGA - 0, Change GSH - + 4.9; SUBJECT 6 Diagnosis - kwashiorkor, Age - 14, Wt - 7.89, Change PGA - +245, Change GSH - -8.7. In four of the subjects, PGA decreased after supplementation while there was a concomitant increase in GSH. One showed no change in PGA excretion and had stopped growing. The other child showed the opposite result. PGA is usually associated with a deficiency of the enzyme GSH synthetase which is reponsible for the synthesis of GSH from glycine and glutamylcysteine. Our results support the hypothesis that if the availability of glycine were low then the reaction catalysed by GSH synthetase would be reduced because of limited substrated, and that the mechanism is effectively the same as with an absence of the enzyme - that is an increased PGA excretion. In this case, glycine corrects the defect. Furthermore, the data provide evidence that rapidly growing children may have an increased requirement for glycine (AU)