Glutamine Metabolism in the Human Newborn

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DESCRIPTION (provided by applicant): 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 actually quantifying changes in glutamine metabolism in relation to ontogeny or acute illness in full term and prematurely born infants. The specific aims of these studies are to examine the systemic and splanchnic metabolism 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 serves as 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 enterocytes (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 management of low birth weight infants.