XAS OF BIOINORGANIC SYSTEMS

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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 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Cr（III）膳食补充剂的抗糖尿病作用可能是通过体内酶促氧化Cr（III）膳食补充剂而产生的致癌Cr（VI），由于Cr（VI）对磷酸酶的强效抑制作用，随后胰岛素活性增加。我们还打算研究人类肺细胞中Cr（VI）生物转化的早期阶段，以补充我们最近在该领域的工作。

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.