STRUCTURE AND MECHANISM OF BIOLOGICAL CHROMIUM

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确定。痕量元素 在葡萄糖代谢中发挥作用，并可能具有其他基本功能 也是。人类的急性和慢性缺陷都得到了承认。这个 老年人特别容易患缺铬症，而且 这些葡萄糖促进剂的一部分人对饮食有反应 铬补充剂可改善葡萄糖耐量。活性铬 络合物(或多个络合物)尚未以纯形式分离，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。这方面的长期目标 项目是分离、表征、合成和阐明 天然铬物种的作用机理。初步努力： 这个研究小组一直致力于评估这一假说 烟酸(烟酸)是活性铬络合物的一部分。 模型化合物的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发展使 两种酵母铬络合物的纯化远远超出了文献报道的水平 之前的调查人员。低分子量材料已经被 部分以化学和光谱技术为特征的。这个 分级铬络合物，在中性时为阴离子，在中性时为阳离子 酸性pH刺激脂肪细胞的葡萄糖氧化，并增加 一个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试验。后一项发现具有 力学意义，并与地质学高度相关 成熟起病的糖尿病患者胰岛素受体的丢失和明显 这种情况下铬缺乏是很常见的。具体项目 目标包括：(1)进一步改进我们的色谱学 扩大到哺乳动物组织的分离程序；(2)化学和 分离络合物的光谱表征；(3)化学 已鉴定的低分子铬配合物的合成；(4) 提高生物合成产率；(5)三种细胞的评价 生物测定方法，以获得机械信息和保证 铬的活度是以很高的特异性来测量的。

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.