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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。三羧酸（TCA）循环中间的底物的变性通量通过α-酮戊二酸酯和谷氨酸酸酯中间导致谷氨酰胺的从头合成。尚未检查这些变化通量的变化是由于蛋白质更新的变化还是外源氨基酸引起的。假设施用较高量的外源氨基酸会增加碳循环到TCA循环中，从而增强了临床稳定（CS）婴儿谷氨酰胺的合成增强，而急性病（AI）的婴儿（AI）无法增加内源性谷氨酰胺的同步。 在拟议的研究中，出生后0-3天（AI）和4-10天（CS）之间检查小于32周的早产婴儿，出生体重小于1500 gm。将使用[5-15-N]谷氨酰胺，[13C15N]亮氨酸示踪剂，作为最佳的恒定速率输注，将检查对谷氨酰胺动力学和亮氨酸动力学和亮氨酸动力学的氮（3 g/kg/d vs 1.5g/kg/d）的反应。此外，将使用[2H5]苯丙氨酸和[15N2]尿素示踪剂来定量蛋白质更新的全身速率和蛋白质不可逆的氧化。肠胃外营养中蛋白质的浓度将增加（从1.5g到3g/kg/d）或减少（从3.0 g到1.5g/kg/d），在开始TPN后19小时。在急性疾病和影响蛋白质代谢期间升高的某些重要细胞因子（TNFα，IL-6）的浓度将在血浆中测量。 研究很重要，因为它们研究了：1）肠胃植物给药氨基酸的数量与谷氨酰胺的从头合成与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）炎性细胞因子的浓度与谷氨酰胺合成与蛋白质更新之间的关系。这些数据将有助于我们理解直接新生儿早产儿中谷氨酰胺和蛋白质代谢的调节，并可能有助于制定这些婴儿营养干预的策略。