OXIDATION OF GLYCINE TO OXALATE

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。 体内合成的草酸盐的量是原发性高尿酸症的关键因素，原发性高尿酸症是一种罕见的遗传性疾病，可导致肾衰竭和过早死亡。草酸盐合成也可能导致特发性草酸钙结石病。导致草酸盐合成的生物化学途径尚未明确定义。40多年前进行的研究表明，氨基酸甘氨酸的代谢可能对内源性草酸盐的合成做出重要贡献。由于所使用的方法，这些结果的解释是不确定的。我们希望使用最先进的技术重新研究甘氨酸的代谢。我们实验室有一台离子色谱仪和一台质谱仪，用于跟踪甘氨酸稳定同位素代谢为乙醇酸、草酸和马尿酸的过程。有了这种灵敏的仪器，我们将能够准确地确定由正常受试者在禁食状态下从甘氨酸合成草酸的量。这些信息将增加我们对导致草酸盐合成的途径的理解，并有可能导致限制草酸盐合成的新策略。

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. The amount of oxalate synthesized in the body is a critical factor in the primary hyperoxalurias, rare genetic diseases that can result in renal failure and premature death. Oxalate synthesis may also contribute to idiopathic calcium oxalate stone disease. The biochemical pathways that result in oxalate synthesis have not been clearly defined. Studies performed over 4 decades ago suggested that the metabolism of the amino acid, glycine, may make an important contribution to endogenous oxalate synthesis. The interpretation of these results is uncertain because of the methodology used. We wish to reinvestigate the metabolism of glycine using state-of-the-art technology. We have in our laboratory an ion chromatograph coupled to a mass spectrometer that will be used to follow the metabolism of a stable isotope of glycine to glycolate, oxalate and hippuric acid. With this sensitive instrumentation we will be able to accurately determine the amount of oxalate synthesized from glycine by normal subjects in the fasted state. This information will increase our understanding of the pathways that lead to oxalate synthesis and has the potential to lead to new strategies to limit oxalate synthesis.