METABOLISM OF THREONINE IN THE VERY LOW BIRTH WEIGHT PREMATURE INFANT

极低出生体重早产儿苏氨酸的代谢

• 批准号: 7378019
• 负责人: PRABHU PARIMI
• 金额: $ 1.01万
• 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/7378019
• 关键词: METABOLISM; THREONINE; 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. Threonine, a non-transaminating essential amino acid, is involved in a number of metabolic processes such as protein synthesis; signal transduction cascades, collagen synthesis and glycine biosynthesis. The catabolism of threonine is complex involving enzymes in the cytoplasmic and in the mitochondrial compartment. Threonine is predominantly metabolized by the splanchnic tissues (liver and gut). Published studies in human adults and in animals suggest developmental differences in threonine catabolism. Studies have also shown that the plasma level of threonine is higher in premature infants receiving parenteral or enteral nutrition. Our data show that premature infants receiving parenteral nutrition have a two-fold increase in the plasma concentration of threonine and higher plasma levels of glycine compared to term infants. It is hypothesized that higher plasma levels of threonine in premature infants are a consequence of higher rate of protein turnover, an enzymatic immaturity of threonine catabolizing enzymes and a lower rate of threonine oxidation. Intravenous administration of exogenous amino acids (parenteral nutrition) bypasses the first pass metabolism of threonine and will lead to a further increase in the plasma level of threonine. Although threonine does not contribute to the synthesis of glycine in newborn infants; a higher level of threonine in premature infants will interfere with metabolism of glycine resulting in higher plasma levels of glycine. In the proposed study, premature infants less than 32 weeks gestation and less than/or equal to 1500 grams birth weight will be recruited. Infants will be studied while they are acutely ill and while growing and receiving full enteral nutrition. Premature infants will be randomized to receive either intravenous glucose solution or total parenteral nutrition containing 3g/kg/d of protein (providing 44 millimol/kg/h of threonine) within 72 hours after birth. Using stable isotopic tracers, the effect of total parenteral nutrition on threonine kinetics, rate of oxidation of threonine, contribution of threonine to glycine, impact of plasma threonine levels on the conversion of glycine to serine and relationship of threonine kinetics to whole body protein turnover and protein oxidation will be examined. In a separate group of growing premature infants, the effect of enteral nutrition (containing 60 millimol/kg/h of threonine) on the above parameters will be examined.

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。苏氨酸是一种非转氨基的必需氨基酸，参与蛋白质合成、信号转导、胶原合成和甘氨酸生物合成等代谢过程。苏氨酸的分解代谢是复杂的，涉及细胞质和线粒体中的酶。苏氨酸主要由内脏组织(肝脏和肠道)代谢。已发表的对成人和动物的研究表明，苏氨酸分解代谢存在发育差异。研究还表明，接受肠外或肠内营养的早产儿血浆苏氨酸水平较高。我们的数据显示，与足月儿相比，接受肠外营养的早产儿的血浆苏氨酸浓度和甘氨酸水平增加了两倍。推测早产儿血浆苏氨酸水平升高是由于蛋白质周转率高、苏氨酸分解代谢酶不成熟和苏氨酸氧化率低所致。静脉注射外源性氨基酸(肠外营养)绕过了苏氨酸的第一次代谢，并将导致血浆苏氨酸水平的进一步增加。虽然苏氨酸不促进新生儿体内甘氨酸的合成，但早产儿体内较高水平的苏氨酸会干扰甘氨酸的代谢，导致血浆中甘氨酸水平升高。在这项拟议的研究中，将招募怀孕32周以下、出生体重小于/或等于1500克的早产儿。将在婴儿病情危重、生长发育并接受充分的肠内营养的同时进行研究。早产儿将在出生后72小时内随机接受静脉葡萄糖溶液或含3g/kg/d蛋白质(提供44毫米/kg/h苏氨酸)的全肠外营养。利用稳定的同位素示踪剂，研究全肠外营养对苏氨酸动力学的影响、苏氨酸的氧化速率、苏氨酸对甘氨酸的贡献、血浆苏氨酸水平对甘氨酸转化为丝氨酸的影响以及苏氨酸动力学与全身蛋白质周转和蛋白质氧化的关系。在另一组生长中的早产儿中，将检查肠内营养(含60毫克/公斤/小时苏氨酸)对上述参数的影响。