Glutamine Metabolism in the Human Newborn

描述（由申请人提供）：谷氨酰胺是一种内源性合成的氨基酸，在急性疾病和极低出生体重（VLBW）婴儿中被认为是“必需的”或“条件必需的”。一些研究者建议在极低出生体重婴儿中使用补充谷氨酰胺，以加速对子宫外环境的适应和从相关新生儿疾病中恢复。然而，没有数据实际量化与足月和早产儿个体发育或急性疾病相关的谷氨酰胺代谢变化。这些研究的具体目的是检查谷氨酰胺的全身和内脏代谢及其与新生儿全身蛋白质/氮和尿素动力学的关系。由于谷氨酰胺是通过α酮戊二酸和谷氨酸的三羧酸循环的分解反应从头合成的，因此假设其代谢将与底物（如葡萄糖和氨基酸）进入三羧酸循环的回补通量密切相关。谷氨酰胺也作为肠细胞和淋巴细胞的重要呼吸燃料。据推测，当肠细胞（和淋巴细胞）增殖时，肠内给药的谷氨酰胺将被局部用于生长中的婴儿的内脏隔室。此外，在新生儿适应期间和低出生体重婴儿从急性疾病中恢复期间，谷氨酰胺将不会局部代谢，并且将绕过内脏隔室。这些假设将通过定量谷氨酰胺在zombination动力学与测量的支链氨基酸，蛋白质周转和尿素合成。将采用稳定同位素示踪剂和气相色谱-质谱法。这些研究将系统地研究在向宫外环境过渡的关键时期和生长过程中，必需氨基酸亮氨酸的转氨作用与必需氨基酸谷氨酰胺的从头合成之间的相互关系，并将为低出生体重儿的营养管理提供代谢基础。

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.