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Systematic analysis of physiological and anti-oxidative function of L-ascorbic acid

L-抗坏血酸生理及抗氧化功能的系统分析

基本信息

批准号：
14560093
负责人：
KURATA Tadao
金额：
$ 2.62万
依托单位：
Niigata University of Pharmacy and Applied Life Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

1) The detailed structural analyses of L-Ascorbic acid (=AsA, Vitamin C) and its related compounds (ex. Dehydro-AsA, monodehydro-AsA, 2,3-diketo-L-gulonic acid, etc.) were carried out from the view point of both experimental and computational chemistry, and basic important data available to analyze the real dynamic structure of these compounds in the actual reaction site.2) The reactivity of AsA and its related compounds with the triplet state oxygen molecule was studied by using the various methods of both experimental and computational chemistry, and the basic data about the major reaction products and reaction mechanisms were obtained.3) As a model enzyme reaction system, hydroxylation reaction of L-proline residue in collagen molecule by prorylhydroxylase was studied, and the outlines of the role of AsA in the biosynthesis process of collagen molecule were elucidated.4) To clarify the effect of passive smoking, a typical oxidative stress, on the biological systems, several animal experiments were carried out. In these experiments, ODS-rats which were unable to synthesize AsA were used as the experimental animals, and the effects of passive smoking and AsA administration on the gene expression of anti-oxidative enzymes in the major organs (Livers and kidneys) of these animals were intensively investigated and some important basic data which were necessary for the systematic analysis of both physiological and anti-oxidative function of AsA were obtained.5) To make this report, re-confirmation of the results of animal experiments described above were made and further additional experiments using DPPH radical reagent were also made, and a new reaction mechanism of radical scavenging function of AsA, the basis of anti-oxidation mechanism of AsA, were clarified for the first time.

1）从实验化学和计算化学的角度对L-抗坏血酸（=AsA、维生素C）及其相关化合物（例如脱氢AsA、单脱氢AsA、2,3-二酮-L-古洛糖酸等）进行了详细的结构分析，为分析这些化合物在实际反应现场的真实动态结构提供了基本的重要数据。2）采用实验化学和计算化学等多种方法对AsA及其三重态氧分子的相关化合物进行了研究，获得了主要反应产物和反应机理的基础数据。 3)作为模型酶反应体系，研究了丙酰羟化酶对胶原蛋白分子中L-脯氨酸残基的羟化反应，概述了AsA在胶原蛋白分子中的作用。阐明了胶原蛋白分子的生物合成过程。4)为了阐明被动吸烟这种典型的氧化应激对生物系统的影响，进行了多项动物实验。在这些实验中，以不能合成AsA的ODS大鼠为实验动物，深入研究了被动吸烟和AsA给药对这些动物主要器官（肝脏和肾脏）抗氧化酶基因表达的影响，获得了系统分析AsA生理和抗氧化功能所必需的一些重要基础数据。5）为此报告，再次证实了上述动物实验结果，并利用DPPH自由基试剂进行了进一步的补充实验，首次阐明了AsA自由基清除功能的新反应机制，这是AsA抗氧化机制的基础。