BRAIN GLUTAMATE METABOLISM--GC/MS STUDIES

脑谷氨酸代谢——GC/MS 研究

基本信息

批准号：
2266639
负责人：
MARC YUDKOFF
金额：
$ 17.58万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-30 至 1995-09-29
项目状态：
已结题

项目摘要

This project involves the study of glutamic acid metabolism in synaptosomes. We will use 15N and 13C as metabolic tracers and gas chromatography-mass spectrometry as an analytic tool to answer these questions: i) How do neurons produce glutamate? Is glutamate the only precursor? Could alanine and the branched-chain amino acids be important N donors? Could 2-oxo-glutarate be an important C donor? ii) How is glutamate synthesis regulated? How is flux through the glutaminase pathway altered during depolarization? What is the effect of Ca2+? Of hypoglycemia? Of hypoxia? iii) How do synaptosomes metabolize glutamate? What is the role of oxidative deamination vs. transamination vs. the purine nucleotide cycle? How is this metabolism altered by hypoglycemia? By hypoxia? By depolarization? A unique feature of the work is our continued use of stable isotopes, particularly 15N, as a metabolic probe for brain nitrogen metabolism and of gas chromatography-mass spectrometry as an analytic tool for the determination of isotopic abundance. The information obtained from this work will provide a new perspective on the metabolism of glutamic acid, the most important excitatory neurotransmitter and the linchpin of all brain nitrogen metabolism. The data also may help us to understand the pathophysiology by which changes in glutamate synthesis and utilization may lead to the irreparable brain damage occurring consequent to anoxia and hypoglycemia, conditions in which glutamate excess is thought to be an important pathophysiologic factor.

该项目涉及研究谷氨酸代谢突触体。我们将使用15N和13C作为代谢示踪剂和气体色谱 - 质谱法作为一种分析工具来回答这些问题：i）神经元如何产生谷氨酸？是谷氨酸是唯一的前体？丙氨酸和分支链氨基酸可能很重要 n捐助者？ 2-氧气 - 谷氨酸可以成为重要的C供体吗？ ii）如何调节谷氨酸合成？如何通过谷氨酰胺酶途径通量在去极化期间发生了变化？ Ca2+有什么影响？的低血糖？缺氧？ iii）突触体如何代谢谷氨酸？氧化脱氨基与嘌呤的作用是什么核苷酸周期？低血糖症如何改变这种新陈代谢？经过缺氧？通过去极化？这项工作的独特功能是我们继续使用稳定的同位素，尤其是15N作为大脑的代谢探针氮代谢和气相色谱质量光谱法作为一种用于确定同位素丰度的分析工具。信息从这项工作中获得的将提供有关的新观点谷氨酸，最重要的兴奋性神经递质和所有脑氮代谢的关键。数据也可以帮助我们了解谷氨酸合成变化的病理生理学和利用可能会导致无法弥补的脑损伤。对于缺氧和低血糖症，认为谷氨酸过量的疾病成为重要的病理生理因素。