This research proposes to test the general hypothesis that reduction in plasma NTPs induced by infection in the malnourished patient results from the compromised synthesis of these protein secondary to a decrease in aromatic amino acids and cysteine availability. A specific hypothesis is that this shortage of aromatic amino acids is due to infection-induced stress response which increases synthesis of other proteins, e.g., acute phase proteins APP and GSH. Studies will be conducted in 6 - 12 month old severely malnourished infants with or without concurrent infection. Using stable isotope tracer technology two experimental protocols will be performed to determine differences in rates of synthesis of several acute phase and nutrient transport proteins, whole body protein synthetic and degradation rates, net protein catabolism and aromatic amino acid (phenylalanine, tyrosine and tryptophan) fluxes in control patients, and infected and uninfected malnourished infants, and to determine differences in cysteine kinetics and rates of synthesis of red blood cell GSH between infected and uninfected malnourished children and those recovered from infection. The results are expected to provide insights into the pathogenesis of reduced plasma NTP and protein metabolism in infected malnourished individuals. The data should also suggest therapeutic approaches to stimulate protein synthesis during early treatment, restore NTP concentrations, and limit whole body protein catabolism.
