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首页> 外文学位 >Protein tyrosine phosphatase 1B: A target for vanadium's insulin-enhancing behavior.
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Protein tyrosine phosphatase 1B: A target for vanadium's insulin-enhancing behavior.

机译：蛋白酪氨酸磷酸酶1B：钒的胰岛素增强行为的目标。

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摘要

My dissertation involves an investigation of the role vanadium-containing compounds play in increasing insulin's efficacy in controlling blood glucose levels. It is well known that certain vanadium-containing compounds function as positive regulators of insulin activity, but the mechanism by which insulin-enhancement occurs has not been fully elucidated. Protein tyrosine phosphatase 1B (PTP 1B), an enzyme shown to play an important role in insulin regulation, negates insulin activity by removing phosphate groups (PO43-) from insulin receptor and other post-receptor substrates involved in the insulin signaling pathway. A plausible explanation is that vanadium-containing compounds inhibit PTP 1B activity, which allows required phosphorylation reactions to proceed normally. My dissertation research is designed to test this hypothesis. A series of specifically modified vanadium-containing compounds have been synthesized, and these compounds strongly inhibit (low micromolar range) a general alkaline phosphatase obtained from calf intestine. A correlation between positive charge on the vanadyl group and inhibition potency of the compound was found. However, a new mode of inhibition against PTP 1B was observed. The kinetic results suggest that the compounds are binding to more than one site on PTP 1B. Additionally, assays using a more physiologically relevant substrate, i.e., a peptide that binds more tightly to PTP 1B, have been completed, where the competitive inhibition results suggest a more positive V=O center improves inhibition potency with one exception. Ultimately, an array of structural and spectroscopic techniques has been utilized to gain a more thorough understanding of the mode of enzyme inhibition. These studies have provided fundamental new knowledge about the biochemistry of phosphatase inhibition and vanadium's insulin-enhancing behavior.
机译：我的论文涉及对含钒化合物在提高胰岛素控制血糖水平的功效中的作用的研究。众所周知，某些含钒化合物起着胰岛素活性的正调节剂的作用，但尚未充分阐明发生胰岛素增强作用的机制。蛋白酪氨酸磷酸酶1B（PTP 1B）是一种在胰岛素调节中起重要作用的酶，它通过从胰岛素受体和其他参与胰岛素信号传导途径的受体后底物中去除磷酸基团（PO43-）来消除胰岛素活性。一个合理的解释是，含钒化合物会抑制PTP 1B活性，从而使所需的磷酸化反应正常进行。我的论文研究旨在检验该假设。已经合成了一系列经过特殊修饰的含钒化合物，这些化合物强烈抑制（低微摩尔范围）从牛小肠获得的一般碱性磷酸酶。发现了钒基上的正电荷与该化合物的抑制能力之间的相关性。但是，观察到一种新的抑制PTP 1B的方式。动力学结果表明该化合物与PTP 1B上的一个以上位点结合。另外，已经完成了使用更具生理相关性的底物，即与PTP 1B更紧密结合的肽进行的测定，其中竞争性抑制结果表明，更积极的V = O中心可改善抑制能力，但有一个例外。最终，已经利用了一系列结构和光谱技术来更全面地了解酶抑制模式。这些研究提供了有关磷酸酶抑制和钒的胰岛素增强行为的生化基础知识。

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  • 作者

    Ziegler, Amanda Joy.;

  • 作者单位

    Loyola University Chicago.;

  • 授予单位 Loyola University Chicago.;
  • 学科 Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 127 p.
  • 总页数 127
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

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