In vivo rates of erythrocyte glutathione synthesis in children with severeprotein-energy malnutrition

Although the compromised GSH status of children with edematous protein-ener gy malnutrition (PEM) has been documented, the in vivo kinetic mechanism(s) responsible for this is not known. To determine if decreased synthesis con tributes to the alteration of GSH homeostasis, the fractional and absolute rates of synthesis of erythrocyte GSH were determined shortly after admissi on (study 1), similar to 9 days postadmission (study 2), and at recovery (s tudy 3) in seven children with edematous PEM and seven children with nonede matous PEM. Children with edematous PEM had significantly lower erythrocyte GSH and slower absolute rates of GSH synthesis than children with nonedema tous PEM both shortly after admission, when they were both malnourished and infected, and similar to 9 days later, when the infection had resolved but they were still malnourished. At these times, the edematous group also had significantly lower erythrocyte GSH concentrations and absolute rates of s ynthesis than at recovery. Plasma and erythrocyte-free cysteine concentrati ons of the edematous group were significantly lower at studies I and 2 than at recovery. In contrast, erythrocyte GSH concentrations, rates of GSH syn thesis, and plasma and erythrocyte free cysteine concentrations of the none dematous group were similar at all three time points and greater at studies 1 and 2 than in the edematous group. These results confirm that GSH defici ency is characteristic of edematous PEM and suggest that this is due to a r educed rate of synthesis secondary to a shortage in cysteine.