PROTEIN METABOLISM IN VERY LOW BIRTH WEIGHT INFANT: EFFECT OF ANAPLEROTIC FLUX

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。底物通过α-酮戊二酸和谷氨酸进入三羧酸(TCA)循环中间体的逆变性通量和引发性流出导致谷氨酰胺从头合成。退变性通量的这些变化是由于蛋白质周转的变化还是由于外源氨基酸的变化还没有得到检验。假设较高数量的外源性氨基酸增加了进入TCA循环的碳流，导致临床稳定(CS)婴儿谷氨酰胺合成增加，而急性疾病(AI)婴儿将不能增加内源性谷氨酰胺合成。在这项拟议的研究中，出生体重小于1500克、小于32周的早产儿将在出生后0-3天(AI)至4-10天(CS)之间进行检查。使用[5-15-N]谷氨酰胺和[13C15N]亮氨酸示踪剂，在最佳恒速输注条件下，研究不同氮量(3g/kg/d和1.5g/kg/d蛋白质)对谷氨酰胺动力学和亮氨酸N和C动力学的响应。此外，将使用[2H5]苯丙氨酸和[15N2]尿素示踪剂来量化蛋白质周转和蛋白质不可逆氧化的全身速率。TPN开始后19h，肠外营养中蛋白质浓度或增加(由1.5g/kg/d增加至3g/kg/d)，或减少(由3.0g/kg/d减少至1.5g/kg/d)。在急性疾病和影响蛋白质代谢的过程中，某些重要的细胞因子(肿瘤坏死因子α、IL-6)的浓度将在血浆中进行测量。这些研究的意义在于：1)肠外注射氨基酸的数量与谷氨酰胺从头合成和蛋白质周转率的关系；2)急性疾病对谷氨酰胺和蛋白质动力学的影响；3)炎性细胞因子浓度与谷氨酰胺合成和蛋白质周转的关系。这些数据将有助于我们了解早产儿在新生儿早期谷氨酰胺和蛋白质代谢的调节，并可能有助于制定对这些早产儿进行营养干预的策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anaplerotic flux of substrates into and cataplerotic efflux of the tricarboxylic acid (TCA) cycle intermediate via alpha-ketoglutarate and glutamate leads to de novo synthesis of glutamine. Whether these changes in anaplerotic flux are due to changes in protein turnover or by exogenous amino acids has not been examined. It is hypothesized that the administration of a higher amount of exogenous amino acids increases anaplerotic flux of carbon into the TCA cycle, resulting in an enhanced synthesis of glutamine in clinically stable (CS) infants, whereas infants who are acutely ill (AI) will not be able to increase endogenous glutamine synthesis. In the proposed study, premature infants less than 32 weeks with birth weight of less than 1500 gm will be examined between 0-3 days (AI) and 4-10 days (CS) after birth. The response to variable amounts of nitrogen (3 g/kg/d vs 1.5g/kg/d of protein) on glutamine kinetics and leucine N and C kinetics will be examined using [5-15-N] glutamine,[13C15N] leucine tracers as at a prime constant rate infusion. In addition, whole body rate of protein turnover and irreversible oxidation of protein will be quantified using [2H5] phenylaline and [15N2] urea tracers. The concentration of protein in the parenteral nutrition will be either increased (from 1.5g to 3g/kg/d) or reduced (from 3.0 g to 1.5g/kg/d) 19 hours after starting TPN. The concentration of certain important cytokines (TNF alpha, IL-6) that are increased during acute illness and impact protein metabolism will be measured in the plasma. The studies are significant in that they examine: 1) the relationship between the quantity of parenterally administered amino acids and de novo synthesis of glutamine and rate of turnover of proteins; 2) the effect of acute illness on glutamine and protein kinetics; and 3) the relationship between the concentration of inflammatory cytokines and glutamine synthesis and protein turnover. These data will contribute to our understanding of the regulation of glutamine and protein metabolism in premature infants in the immediate newborn period, and may help develop strategies for nutrient intervention in these infants.