EXCEEDTHE SPACE PROV DED. Glutamine, an endogenously synthesized amino acid, has been variously considered 'essential' or 'conditionally essential' during acute illness and in very low birth weight (VLBW) infants. Several investigators have proposed the use of supplemental glutamine in VLBW babies in order to accelerate adaptation to extrauterine environment and recovery from related neonatal illness. However, there are no data _ctually quantifying changes in glutamine metabolism in relation to ontogeny or acute illness in full term and _rematurely born infants.
The specific aims of these studies are to examine the systemic and splanchnic _etabolism of glutamine, and its relation to whole body protein/nitrogen and urea kinetics in the neonate. Since glutamine is synthesized de novo via a cataplerotic reaction of the tricarboxylic acid cycle from alphaketoglutarate and glutamate, it is hypothesized that its metabolism will be closely linked with the anaplerotic flux of substrates such as glucose and amino acids into the tricarboxylic acid cycle. Glutamine also _ervesas an important respiratory fuel for the enterocytes and the lymphocytes. It is hypothesized that enterally administered glutamine will be utilized locally in the splanchnic compartment in growing infants when the :nterocytes (and lymphocytes) are proliferating. Furthermore, during neonatal adaptation and during recovery from acute illness in the low birth weight baby, glutamine will not be locally metabolized and will bypass the splanchnic compartment. These hypotheses will be examined by quantifying the kinetics of glutamine in zombination with measurements of the transamination of branched chain amino acids, protein turnover and urea synthesis. Stable isotopic tracers and gas chromatograph-mass spectrometric methods will be employed. These studies will systematically examine the interrelationship between the transamination of an essential amino acid, leucine, and the de novo synthesis of a dispensable amino acid, glutamine, during the critical period of ransition to extrauterine environment and during growth, and will provide a metabolic basis for nutritional nanagement of low birth weight infants. PERFORMANCE SITE ========================================Section End===========================================

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Nutrition Study Section (NTN)
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Raju, Tonse N
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Case Western Reserve University
Schools of Medicine
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Kalhan, Satish C (2016) One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health. Mol Cell Endocrinol 435:48-60
Kalhan, S C; Wilson-Costello, D (2013) Prematurity and programming: contribution of neonatal Intensive Care Unit interventions. J Dev Orig Health Dis 4:121-33
Kalhan, Satish C (2013) One-carbon metabolism, fetal growth and long-term consequences. Nestle Nutr Inst Workshop Ser 74:127-38
Kalhan, Satish C; Marczewski, Susan E (2012) Methionine, homocysteine, one carbon metabolism and fetal growth. Rev Endocr Metab Disord 13:109-19
Dasarathy, Jaividhya; Gruca, Lourdes L; Bennett, Carole et al. (2010) Methionine metabolism in human pregnancy. Am J Clin Nutr 91:357-65
Kalhan, Satish C (2009) Optimal protein intake in healthy infants. Am J Clin Nutr 89:1719-20
Nye, Colleen K; Hanson, Richard W; Kalhan, Satish C (2008) Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat. J Biol Chem 283:27565-74
Kalhan, Satish C; Bugianesi, Elisabetta; McCullough, Arthur J et al. (2008) Estimates of hepatic glyceroneogenesis in type 2 diabetes mellitus in humans. Metabolism 57:305-12
Kalhan, Satish C; Bier, Dennis M (2008) Protein and amino acid metabolism in the human newborn. Annu Rev Nutr 28:389-410
Thomas, Biju; Gruca, Lourdes L; Bennett, Carole et al. (2008) Metabolism of methionine in the newborn infant: response to the parenteral and enteral administration of nutrients. Pediatr Res 64:381-6

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