Plasma l-5-oxoproline kinetics and whole blood glutathione synthesis rates in severely burned adult humans

Abstract

Compromised glutathione homeostasis is associated with increased morbidity in various disease states. We evaluated the kinetics of l-5-oxoproline, an intermediate in the γ-glutamyl cycle of glutathione production, in fourteen severely burned adults by use of a primed, constant intravenous infusion of l-5-[1-13C]oxoproline. In nine of these patients, whole blood glutathione synthesis and plasma kinetics of glycine and leucine were also measured with [15N]glycine andl-[2H3]leucine tracers. Patients were studied under a “basal” condition that provided a low dose of glucose and total parenteral nutrition. For comparison with control subjects, whole blood glutathione synthesis was estimated in six healthy adults. Burn patients in a basal condition showed significantly higher rates of plasma oxoproline clearance and urinaryd- and l-oxoproline excretion compared with fasting healthy control subjects. Whole blood glutathione concentration and absolute synthesis rate in the basal state were lower than for control subjects. Total parenteral feeding without cysteine but with generous methionine did not affect oxoproline kinetics or whole blood glutathione synthesis. The estimated rate of glycine de novo synthesis was also lower in burn patients, suggesting a possible change in glycine availability for glutathione synthesis. The roles of precursor amino acid availability, as well as alterations in metabolic capacity, in modulating whole blood glutathione production in burns now require investigation.