STRUCTURE AND MECHANISM OF BIOLOGICAL CHROMIUM

生物铬的结构与作用机制

• 批准号: 3232097
• 负责人: HAROLD M. GOFF
• 金额: $ 9.02万
• 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 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232097
• 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; 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参与现在很好 通过临床和营养研究建立。 跟踪元素 在葡萄糖代谢中起作用，可能具有其他基本功能 也是如此。 认识到急性和慢性人类缺陷。 这 老年人特别容易受到铬缺乏症的影响，很大 这些葡萄糖智能个体的一部分对饮食有反应 铬补充剂具有提高的葡萄糖耐受性。 活性铬 复杂（或复合物）尚未以纯形式隔离，并且 材料在结构上保持不明。 分子基础 作用和生物合成途径是不确定的。 长期目标 项目将分离，表征，合成和阐明 天然铬物种的作用机理。 初步努力 该研究小组已致力于评估假设 烟酸（烟酸）是活性铬复合物的一部分。 模型化合物结果没有提供任何有利于这一假设的证据。 在该实验室中开发改进的隔离方法已允许 两个酵母铬复合物的纯化远远超出了 先前的调查人员。 低分子重量材料已经 部分以化学和光谱技术为特征。 这 分离的铬配合物，在中性pH和阳离子上是阴离子的 酸pH通过脂肪细胞刺激葡萄糖氧化，并增加 在朋友中，明显的胰岛素受体数量为2.5 红细胞血压素细胞胰岛素结合测定。 后一个发现有 机械意义，与 到期胰岛素受体的丧失和明显 铬缺乏在这种情况下很常见。 具体项目 目标包括：（1）我们色谱的进一步改进 分离程序，扩展到哺乳动物组织； （2）化学和 分离的复合物的光谱表征； （3）化学 鉴定出的低分子量铬复合物的合成； （4） 改善生物合成产量； （5）评估三个细胞 生物测定方法以获取机械信息和保证 铬活性以高特异性进行测量。