METABOLISM AND NEUROCHEMISTRY OF LYSINE IN THE BRAIN

大脑中赖氨酸的代谢和神经化学

• 批准号: 3394606
• 负责人: YUNG-FENG CHANG
• 金额: $ 7.24万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3394606
• 关键词: aminoacid metabolism; aminoacid transport; brain metabolism; chromatography; glia; lysine; nerve endings; neurochemistry; neurotransmitter metabolism; piperidine; synaptic vesicles; synaptosomes

The broad objectives of this research project are to study the metabolism of lysine in the rat brain, to measure the endogenous contents of lysine mtabolites in the whole brain, to examine the subcellular distribution of lysine metabolites and their metabolizing enzymes in the brain tissues, and to synthesize the non-commercially available lysine metabolites for research use. A study is proposed to test the hypothesis that piperidine is formed from L-lysine via Delta1-piperideine by "abortive transamination." Experiments are also proposed to examine the possibility of enzyme-bound intermediates in the metabolism of L-lysine to L-pipecolate. Properties of the enzymes involved in the metabolism of L-lysine in the brain will be studied with the design of new and sensitive assay methods. The endogenous contents of lysine metabolites and their metabolizing enzymes will be studied in the whole brain as well as subcellular cortical fractions. Examination of the possible association of lysine metabolites and/or their enzymes with the nerve endings and synaptic vesicles will be performed with the technique of density gradient centrifugation. Isotopically labeled lysine metabolites will be used for the study of uptake and distribution of these metabolites into the subcellular fractions in order to augment results obtained from the endogenous distribution study. Synthesis of lysine metabolites, both labeled and unlabeled, will utilize microbial, enzymatic as well as organic synthesis techniques. It is hoped that the knowledge obtained in this work will help understand the etiology of human genetic disorders related to brain lysine metabolism, and the role of lysine and its metabolites play in sedation, sleep, and other neuronal functions related to neurological disorders.

该研究项目的广泛目标是研究新陈代谢 大鼠大脑中的赖氨酸，测量赖氨酸的内源性含量 整个大脑中的mtabolites，检查 赖氨酸代谢产物及其代谢酶在脑组织中，以及 综合非公务可用的赖氨酸代谢物的 研究用途。 提出了一项研究以检验哌啶的假设 由delta1-Piperideine由“流产 还提出了实验来检查可能性 L-赖氨酸代谢中的酶结合的中间体 L-Pipecaly。 参与代谢的酶的特性 将研究大脑中的l-赖氨酸，并设计新的和敏感的 测定方法。 赖氨酸代谢产物及其的内源性含量 将在整个大脑中研究代谢酶 亚细胞皮质分数。 检查可能的关联 赖氨酸代谢物和/或其神经末端和突触的酶 囊泡将使用密度梯度技术进行 离心。 同位素标记的赖氨酸代谢物将用于 这些代谢产物摄取和分布到 亚细胞分数以增加从 内源分发研究。 赖氨酸代谢产物的合成，两者都 标记和未标记，将使用微生物，酶促和有机物 合成技术。 希望在这项工作中获得的知识 将有助于了解与人类遗传疾病有关的病因 脑赖氨酸代谢，赖氨酸及其代谢的作用在 镇静，睡眠和其他与神经系统有关的神经元功能 疾病。