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

极低出生体重婴儿的蛋白质代谢：回补通量的影响

• 批准号: 7377989
• 负责人: SATISH C KALHAN
• 金额: $ 5.95万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377989
• 关键词: PROTEIN; METABOLISM; VERY; LOW; BIRTH

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。底物通过α-酮戊二酸和谷氨酸进入三羧酸（TCA）循环中间体的回补流和回补流出导致谷氨酰胺的从头合成。回补通量的这些变化是否是由于蛋白质周转的变化或外源氨基酸的变化尚未研究。据推测，给予更高含量的外源性氨基酸会增加进入三羧酸循环的碳回补通量，导致临床稳定（CS）婴儿的谷氨酰胺合成增强，而急性病（AI）婴儿将无法增加内源性谷氨酰胺合成。 在拟定的研究中，将在出生后0-3天（AI）和4-10天（CS）检查出生体重小于1500 gm的32周以下早产儿。将使用[5-15-N]谷氨酰胺、[13 C15 N]亮氨酸示踪剂，以初始恒定速率输注，检查不同量氮（3 g/kg/d vs 1.5 g/kg/d蛋白质）对谷氨酰胺动力学以及亮氨酸N和C动力学的反应。此外，将使用[2 H5]苯丙氨酸和[15 N2]尿素示踪剂定量全身蛋白质周转率和蛋白质的不可逆氧化。开始TPN后19小时，胃肠外营养中的蛋白质浓度将增加（从1.5 g/kg/d增加至3 g/kg/d）或降低（从3.0 g/kg/d减少至1.5 g/kg/d）。将在血浆中测量急性疾病期间增加并影响蛋白质代谢的某些重要细胞因子（TNF α、IL-6）的浓度。 这些研究的重要性在于，它们检查了：1）胃肠外给药氨基酸的量与谷氨酰胺从头合成和蛋白质周转率之间的关系; 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率之间的关系。这些数据将有助于我们了解的调节谷氨酰胺和蛋白质代谢的早产儿在新生儿期，并可能有助于制定战略，营养干预这些婴儿。