XAS OF BIOINORGANIC SYSTEMS

生物无机系统的 XAS

• 批准号: 7598150
• 负责人: PETER A LAY
• 金额: $ 0.28万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598150
• 关键词: Area; Binding; Cardiac Myocytes; Cardiovascular Diseases; Cells; Complement; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Environment; Enzymes; Freezing; Funding; Grant; Heme; Hemoglobin; Human; Hydrogen Peroxide; Institution; Insulin; Lead; Lung; Metabolic Biotransformation; Monitor; Muscle Cells; Myoglobin; Phosphoric Monoester Hydrolases; Precipitation; Prevention; Process; Protein Binding; Proteins; Raman Spectrum Analysis; Reaction; Research; Research Personnel; Resources; Source; Staging; Structure; System; Techniques; Thinking; United States National Institutes of Health; Work; adduct; chromium hexavalent ion; diabetic; dietary supplements; in vivo; mutant; oxidation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Changes in the heme environment when the a-hemoglobin stabilizing protein (AHSP) binds to a-hemoglobin (a-Hb), which we have studied by Raman spectroscopy, will be monitored by Fe K-edge XAFS. Such binding is important in prevention of toxic heme precipitation from unstable oxy-a-Hb, but all crystal structures of AHSP:oxy-a-Hb complexes contain mutant Hb and it is not clear whether the structures are the same as with the wild type because they have different reactivities. Fe K-edge XAFS will also be used to study the reactions of myoglobin with H2O2 in cardiac myocytes. Such processes are thought to lead ultimately to cardiovascular disease and XAS will be recorded on snap frozen cell pellets of the myocytes (using previously developed techniques) that are untreated or H2O2-treated and changes in the Mb XAS will be monitored. Cr K-edge XAFS will be recorded on Cr(VI) adducts of phosphatase enzymes (for which there are no structural data), since we have recently shown that anti-diabetic effects of commonly used Cr(III) dietary supplements are likely to be exerted by in-vivo enzymatic oxidation of the Cr(III) dietary supplements to carcinogenic Cr(VI), followed increased insulin activity due to potent Cr(VI) inhibition of phosphatase enzymes We also intend to study the very early stages of the biotransformations of Cr(VI) in human lung cells to complement our recent work in the area.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 当α-血红蛋白稳定蛋白（AHSP）与α-血红蛋白（α-Hb）结合时，血红素环境的变化，我们已经用拉曼光谱研究过，将用Fe K边XAFS监测。这种结合对于防止不稳定的氧合-α-Hb沉淀出有毒的血红素是重要的，但是血红蛋白稳定蛋白：氧合-α-Hb复合物的所有晶体结构都含有突变的Hb，并且由于它们具有不同的反应性，因此不清楚它们的结构是否与野生型相同。 Fe K边XAFS也将用于研究心肌细胞中肌红蛋白与H_2O_2的反应。 这些过程被认为最终导致心血管疾病，并且XAS将记录在未经处理或H2 O2处理的肌细胞的快速冷冻细胞团块上（使用先前开发的技术），并且将监测Mb XAS的变化。Cr K边XAFS将记录在磷酸酶的Cr（VI）加合物上（没有结构数据），因为我们最近表明常用的铬（III）膳食补充剂的抗糖尿病作用可能是通过体内酶促氧化铬（III）膳食补充剂产生致癌的铬（VI），随后由于Cr（VI）对磷酸酶的有效抑制而增加胰岛素活性。我们还打算研究Cr（VI）在人肺细胞中生物转化的非常早期阶段，以补充我们最近在该领域的工作。