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ACID-BASE BALANCE REGULATION OF RENAL METABOLISM

肾脏代谢的酸碱平衡调节

基本信息

批准号：
3151135
负责人：
DAVID P SIMPSON
金额：
$ 16.83万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-12-01 至 1989-11-30
项目状态：
已结题

项目摘要

This project is an investigation into regulation of intermediary metabolism in the kidney by acid-base changes and the relationship to physicologic processes involved in acid-base homeostasis. The emphasis in the project is to relate properties of the inner mitochondrial membrane to two different metabolic responses by the kidney to alterations in acid-base balance. (1) During chronic metabolic acidosis renal ammoniagenesis from glutamine increases strikingly. Previous work has suggested that a major factor in this adaptive response is an increase in acidosis in glutamine transport by its carrier in the inner mitochondrial membrane, leading to delivery of more glutamine to phosphate dependent glutaminase. Further evidence for adaptation of the glutamine transporter will be sought in studies on mitochondria from dogs with chronic metabolic or respiratory acidosis. Changes in mitochondrial glutamine transport and metabolism will be correlated with NH4+excretion, NH3 synthesis and glutamine utilization in intact animals with chronic metabolic or respiratory acidosis. (2) Levels in renal cortex of a number of citric acid cycle and related substrates decrease in acute metabolic acidosis and increase in metabolic alkalosis. We postulate that these changes are the result of substrate shifts occurring in response to variations in the mitochondrial pH gradient. Studies will be carried out in isolated kidney tubules and in mitochondria to determine the validity of this hypothesis.

本项目是对中间代谢调节的研究酸碱变化对肾脏的影响及其与生理与酸碱平衡有关的过程。项目的重点是将线粒体内膜的特性与两个肾脏对酸碱平衡改变的不同代谢反应平衡 (1)在慢性代谢性酸中毒期间，谷氨酰胺显著增加。以前的研究表明，一个主要的这种适应性反应中的一个因素是谷氨酰胺酸中毒的增加通过线粒体内膜中的载体运输，导致向磷酸盐依赖性谷氨酰胺酶递送更多的谷氨酰胺。进一步谷氨酰胺转运蛋白的适应性证据将在慢性代谢性或呼吸性疾病犬线粒体的研究酸中毒线粒体谷氨酰胺转运和代谢的变化将与NH_4 ~+排泄、NH_3合成和谷氨酰胺利用有关在患有慢性代谢性或呼吸性酸中毒的完整动物中。（二）肾皮质中柠檬酸循环的数量和相关水平急性代谢性酸中毒底物减少，代谢性酸中毒底物增加 - 是的我们假定这些变化是底物作用的结果。响应于线粒体pH值变化而发生的变化梯度离心研究将在离体肾小管中进行，线粒体来确定这一假设的有效性。