DIETARY PROTEIN AND ENDOGENOUS OXALATE SYNTHESIS

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。 草酸钙是一种罕见的遗传性疾病，体内合成的草酸量是原发性高草酸尿症的关键因素，也是草酸钙肾结石形成的重要因素。促进草酸内源合成的代谢途径和饮食成分还没有明确的定义。肝脏是产生内源性草酸的主要器官，我们实验室培养的肝细胞实验表明，氨基酸代谢是这种草酸的主要来源。我们假设氨基酸代谢是人类内源性草酸产生的一个重要因素，这种代谢在高蛋白饮食中会得到加强。我们之前进行的一项研究表明，女性，而不是男性，会通过增加内源性草酸合成来应对蛋白质摄入量的增加。然而，由于缺乏对膳食草酸的控制，这项研究的解释是混乱的。为了验证我们的假设，即氨基酸代谢是男性和女性内源性草酸合成的重要贡献者，我们将检查消费不同蛋白质含量饮食的受试者尿中草酸的排泄情况。将控制饮食中的宏观和微量营养素，包括草酸，以限制饮食草酸对尿草酸排泄的影响。

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.