DIETARY PROTEIN AND ENDOGENOUS OXALATE SYNTHESIS

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。子项目及 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。 体内草酸盐的合成量是原发性高尿酸症的一个关键因素，这是一种罕见的遗传性疾病，也在草酸钙肾结石的形成中起重要作用。 代谢途径和饮食成分，有助于这种内源性合成的草酸盐尚未明确界定。 肝脏是产生内源性草酸盐的主要器官，我们实验室用培养的肝细胞进行的实验表明，氨基酸代谢是这种草酸盐的主要来源。 我们假设氨基酸代谢是人体内源性草酸盐产生的重要因素，并且这种代谢在高蛋白饮食中会增强。我们以前的一项研究表明，女性，而不是男性，响应增加蛋白质摄入量增加的内源性合成草酸盐。然而，由于缺乏对饮食草酸盐的控制，这项研究的解释受到了混淆。为了检验我们的假设，即氨基酸代谢是一个显着的贡献者内源性草酸合成的男性和女性，我们将检查尿排泄的草酸在受试者消耗不同的蛋白质含量的饮食。将控制饮食中的大量和微量营养素，包括草酸盐，以限制饮食中草酸盐对尿草酸盐排泄的影响。

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, which are rare genetic diseases, and also plays an important role in calcium oxalate kidney stone formation. The metabolic pathways and dietary constituents that contribute to this endogenous synthesis of oxalate have not been clearly defined. The liver is the major organ producing endogenous oxalate and experiments in our laboratory with cultured hepatocytes indicate that amino acid metabolism is a primary source of this oxalate. We hypothesize that amino acid metabolism is an important contributor to endogenous oxalate production in humans and that this metabolism will be enhanced on high protein diets. A previous study we conducted suggested that females, but not males, responded to an increased protein intake with an increased endogenous synthesis of oxalate. The interpretation of this study was confounded, however, by a lack of control of dietary oxalate. To test our hypothesis that amino acid metabolism is a significant contributor to endogenous oxalate synthesis in both males and females, we will examine the urinary excretion of oxalate in subjects consuming diets of varying protein content. Diets will be controlled in macro- and micronutrients, including oxalate, to limit the effects of dietary oxalate on urinary oxalate excretion.