STRUCTURE AND MECHANISM OF BIOLOGICAL CHROMIUM

生物铬的结构与作用机制

• 批准号: 3152898
• 负责人: HAROLD M. GOFF
• 金额: $ 9.04万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152898
• 关键词: adipocytes; chemical structure function; cholesterol; chromium; dietary trace element; glucose metabolism; glucose tolerance test; glycosuria; hyperglycemia; hypoglycemia; metal complex; metal metabolism disorder; metalloenzyme; nicotinate; nutrition related tag; triglycerides; vitamin B12

Involvement of chromium in human and animal nutrition is now well established through clinical and nutritional studies. The trace element plays a role in glucose metabolism and may have other essential functions as well. Both acute and chronic human deficiencies are recognized. The elderly are especially susceptible to chromium deficiency, and a large fraction of these glucose-intelerant individuals respond to dietary chromium supplements with improved glucose tolerance. The active chromium complex (or complexes) has not yet been isolated in pure form, and the material remains structurally uncharacterized. The molecular basis of action and biosynthesis pathways are undefined. Long-term goals of this project are to isolate, characterize, synthesize, and elucidate the mechanism of action of the native chromium species. Preliminary efforts by this research group have been directed toward evaluation of the hypothesis that nicotinic acid (niacin) was a part of the active chromium complex. Model compound results provide no evidence to favor this hypothesis. Development of improved isolation methods in this laboratory has allowed purification of two yeast chromium complexes well beyond levels reported by previous investigators. The low-molecular-weight materials have been partially characterized by chemical and spectroscopic techniques. The fractionated chromium complex that is anionic at neutral pH and cationic at acid pH stimulates glucose oxidation by adipocytes, and increases the apparent number of insulin receptors by a factor of 2.5 in a Friend erythroleukemia cellular insulin binding assay. This latter finding has mechanistic significance and is highly relevant to the tiology of maturity-onset diabetes in that loss of insulin receptors and apparent chromium deficiency are common for this condition. Specific project objectives include: (1) further improvements in our chromatographic isolation procedures with extension to mammalian tissues; (2) chemical and spectroscopic characterization of isolated complexes; (3) chemical synthesis of identified low-molecular-weight chromium complexes; (4) improvement of biosynthetic yields; and (5) evalution of three cellular bioassay methods in order to gain mechanistic information and assurance that chromium activity is being measured with high specificity.

铬在人类和动物营养中的作用现在很好 通过临床和营养研究建立。 微量元素 在葡萄糖代谢中起作用，并可能具有其他基本功能 也 急性和慢性人体缺陷都得到承认。 的 老年人特别容易缺铬， 这些葡萄糖intelerant个体的一部分响应饮食 铬补充剂具有改善的葡萄糖耐量。 活性铬 复合物（或复合物）尚未以纯形式分离， 材料在结构上仍然没有特征。 的分子基础 作用和生物合成途径是不确定的。 长期目标 项目是分离，表征，合成和阐明 天然铬物种的作用机制。 初步努力 这个研究小组一直致力于评估假设， 烟酸是活性铬络合物的一部分。 模型化合物结果未提供支持该假设的证据。 在这个实验室里，改进的隔离方法的发展使得 两种酵母铬络合物的纯化远远超过了 以前的调查员。 低分子量材料已经被 通过化学和光谱技术部分表征。 的 分级的铬络合物，其在中性pH下为阴离子， 酸性pH刺激脂肪细胞对葡萄糖的氧化， 胰岛素受体的表观数量在朋友中增加了2.5倍 红白血病细胞胰岛素结合测定。 后一项发现 机械的意义，并高度相关的组织学， 成熟型糖尿病在胰岛素受体和明显的损失 铬缺乏症是常见的这种情况。 具体项目 目标包括：（1）进一步改进我们的色谱 （2）化学分离方法， 分离的络合物的光谱表征;（3）化学 鉴定的低分子量铬络合物的合成;（4） 提高生物合成产率;（5）评价三种细胞 生物测定方法，以获得机械信息和保证 铬的活性是以高特异性测量的。