RENAL BASIS FOR HYPOCITRATURIA

低柠檬酸尿症的肾脏基础

• 批准号: 6121189
• 负责人: ROBERT J ALPERN
• 金额: $ 0.82万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121189
• 关键词: Mammalia; biomedical resource; nuclear magnetic resonance spectroscopy; technology /technique; urinary tract

Urinary citrate is a key inhibitor of nephrolithiasis, and thus its concentration in the urine is of great importance. The amount of citrate in the urine is determined primarily by the rate of proximal tubular citrate absorption. In this nephron segment, citrate is reabsorbed across the luminal membrane, and is then metabolized. In previous studies, we and others have identified two potential pathways of proximal tubule citrate metabolism: 1) a cytoplasmic pathway involving metabolism by ATP citrate lyase; and 2) a mitochondrial pathway involving metabolism in the citric acid cycle. Both of these pathways are up-regulated in hypocitraturic conditions. However, it is not presently known which of these pathways is quantitatively more important. 13C NMR provides an excellent method to examine the pathway of citrate metabolism in the renal cortex (which is comprised mostly of proximal tubule). The purpose of these studies was to examine whether this approach is feasible, and to determine if blood citrate is oxidized in the kidney in vivo. Rats were infused with [2,3,4-13C] citrate and at the end of the infusion period, a laparatomy was performed and the kidneys and liver freeze-clamped and extracted. The 13C NMR data demonstrate that following infusion of [2,3,4-13C] citrate, spin-spin coupling was observed in the C2, C3, and C4 signals of renal glutamate. This spin-spin coupling proves that the renal signal is derived from the infused [2,3,4-13C] citrate. No spin-spin coupling in the glutamate resonances were found in the liver spectrum indicating little if any hepatic metabolism of the infused tracer citrate. This is consistent with the dogma in the field that the liver does not take up citrate from the extracellular fluid. These results demonstrate that extracellular citrate is oxidized by the kidney in vivo, but oxidation of citrate by the liver could not be detected in the same animals. (Collaborative 6) REPORT PERIOD: (09/01/97-08/31/98)

尿柠檬酸盐是肾结石的关键抑制物，因此 它在尿液中的浓度非常重要。金额的多少 尿液中的柠檬酸主要由近端的 管状柠檬酸盐吸收。在这段肾单位中，柠檬酸是 通过管腔膜重吸收，然后代谢。在……里面 在之前的研究中，我们和其他人已经确定了两条潜在的途径 近端小管柠檬酸代谢：1)细胞质途径 参与ATP柠檬酸裂解酶的代谢；2)线粒体 柠檬酸循环中涉及代谢的途径。这两个都是 在低柠檬酸的情况下，通路被上调。然而，它 目前尚不清楚这些途径中哪一条在数量上更多 很重要。~(13)C核磁共振提供了一种很好的方法来研究 肾皮质柠檬酸代谢途径(包括 主要是近端小管)。这些研究的目的是 检查这种方法是否可行，并确定血液是否 柠檬酸在体内的肾脏中被氧化。给大鼠注射了 [2，3，4-13C]柠檬酸盐，在输液期结束时， 进行了腹腔镜手术，肾脏和肝脏被冷冻夹住并 提取出来的。~(13)C核磁共振数据表明 [2，3，4-13C]柠檬酸，在C2，C3， 肾脏谷氨酸的C4信号。这种自旋-自旋耦合证明了 肾脏信号来自注入的[2，3，4-13C]柠檬酸盐。 在谷氨酸共振中没有发现自旋-自旋耦合。 肝脏光谱显示，即使有肝脏代谢，也很少 注入的柠檬酸示踪剂。这与《纽约时报》中的教条一致 肝脏不从细胞外吸收柠檬酸的领域 流体。这些结果表明，胞外柠檬酸盐是 体内被肾脏氧化，但柠檬酸被肝脏氧化 在相同的动物身上检测不到。(协作6)报告 期间：(09/01/97-08/31/98)