Both our work and that of other investigators have shown that protein catabolic states such as severe burn injury is accompanied by a stimulated rate of glycolysis. It is our hypothesis that this stimulated rate of glycolysis is the underlying cause of the increased loss of protein, because it elicits a suppression of protein synthesis rate via the following mechanism. Stimulation of the rate of glycolysis leads to an increased non-oxidative disposal of pyruvate, derived alanine from peripheral tissues. This reduces the availability of intracellular nitrogen (N) for glutamine synthesis, thereby causing a depletion of the intracellular glutamine pool which in turn elicits a suppression of muscle protein synthetic rate. Secondly, we will test the hypothesis that cortisol and insulin exert their effect on protein metabolism via this proposed mechanism. To test this hypothesis we will used the intact dog hindlimb model to examine the dynamics of these interrelationships by manipulating the rate of glycolysis and determining its effects on lactate and alanine fluxes across the muscle bed, intracellular glutamine concentrations and muscle protein synthesis rate. Somatostatin will be infused centrally to suppress insulin and glucagon secretion at the wholebody level and glucagon plus epinephrine infused in the femoral artery of the experimental limb at a high dose to stimulate the rate of glycolysis. Isotopes of pyruvate and leucine will be used to measure rate of glycolysis (pyruvate Ra) and muscle protein synthesis rate. These studies will help us better understand the mechanism by which protein metabolism is altered in severe stressed states.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Morlese, J F; Forrester, T; Del Rosario, M et al. (1997) Transferrin kinetics are altered in children with severe protein-energy malnutrition. J Nutr 127:1469-74
Morlese, J F; Forrester, T; Badaloo, A et al. (1996) Albumin kinetics in edematous and nonedematous protein-energy malnourished children. Am J Clin Nutr 64:952-9
Wykes, L J; Fiorotto, M; Burrin, D G et al. (1996) Chronic low protein intake reduces tissue protein synthesis in a pig model of protein malnutrition. J Nutr 126:1481-8
Jahoor, F; Sivakumar, B; Del Rosario, M et al. (1996) Isolation of acute-phase proteins from plasma for determination of fractional synthesis rates by a stable isotope tracer technique. Anal Biochem 236:95-100
Jahoor, F; Bhattiprolu, S; Del Rosario, M et al. (1996) Chronic protein deficiency differentially affects the kinetics of plasma proteins in young pigs. J Nutr 126:1489-95
Jahoor, F; Wykes, L J; Reeds, P J et al. (1995) Protein-deficient pigs cannot maintain reduced glutathione homeostasis when subjected to the stress of inflammation. J Nutr 125:1462-72
Jahoor, F; Burrin, D G; Reeds, P J et al. (1994) Measurement of plasma protein synthesis rate in infant pig: an investigation of alternative tracer approaches. Am J Physiol 267:R221-7
Jahoor, F; Zhang, X J; Frazer, E (1994) Mechanisms by which dichloroacetate lowers lactic acid levels: the kinetic interrelationships between lactate, pyruvate, alanine, and glucose. Proc Soc Exp Biol Med 205:44-51
Jahoor, F; Zhang, X J; Baba, H et al. (1992) Comparison of constant infusion and flooding dose techniques to measure muscle protein synthesis rate in dogs. J Nutr 122:878-87