XAS OF BIOINORGANIC SYSTEMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们用拉曼光谱研究了α-血红蛋白稳定蛋白(AHSP)与α-血红蛋白(a-Hb)结合时血红素环境的变化，将用Fe K边XAFS来监测。这种结合对于防止不稳定的oxy-a-Hb产生有毒的血红素沉淀是很重要的，但AHSP：Oxy-a-Hb的所有晶体结构都含有突变的Hb，目前尚不清楚这些结构是否与野生型相同，因为它们具有不同的反应活性。Fe K-EDGE XAFS还将用于研究心肌细胞中肌红蛋白与过氧化氢的反应。这种过程被认为最终会导致心血管疾病，XAS将被记录在未经处理或经过氧化氢处理的心肌细胞的Snap冷冻细胞球上(使用先前开发的技术)，并将监测Mb XAS的变化。CrK-Edge XAFS将被记录在磷酸酶(没有结构数据)的铬(VI)加合物上，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将铬(III)膳食补充剂氧化成致癌的铬(VI)，随后由于有效的铬(VI)抑制磷酸酶而提高胰岛素活性。我们还打算研究铬(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。

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.