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

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已得到很好的证实 通过临床和营养研究建立。 微量元素 在葡萄糖代谢中发挥作用，并可能具有其他重要功能 以及。 人类的急性和慢性缺陷都是公认的。 这 老年人特别容易缺铬，并且大量 这些葡萄糖不耐受个体中的一小部分对饮食有反应 铬补充剂可改善葡萄糖耐量。 活性铬 复合物（或复合物）尚未以纯形式分离出来，并且 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尚不明确。 本次活动的长期目标 项目的目的是分离、表征、综合和阐明 天然铬物质的作用机制。 初步努力 该研究小组致力于评估该假设 烟酸（烟酸）是活性铬络合物的一部分。 模型化合物结果没有提供支持这一假设的证据。 该实验室改进的分离方法的开发使得 两种酵母铬复合物的纯化远远超出了报道的水平 以前的调查员。 低分子材料已 部分通过化学和光谱技术进行表征。 这 分馏铬络合物，在中性 pH 值下呈阴离子，在 酸性 pH 值会刺激脂肪细胞对葡萄糖的氧化，并增加 朋友的胰岛素受体表观数量增加了 2.5 倍 红白血病细胞胰岛素结合测定。 后一个发现有 机械意义，并与tiology高度相关 成熟期发病的糖尿病，胰岛素受体的丧失和明显的 这种情况常见于缺铬。 具体项目 目标包括： (1) 进一步改进我们的色谱 延伸至哺乳动物组织的隔离程序； (2)化学和 分离复合物的光谱表征； (3)化学 已鉴定的低分子量铬络合物的合成； (4) 提高生物合成产量； (5) 三种细胞的评估 生物测定方法以获得机械信息和保证 正在以高特异性测量铬活性。