CARBON DIOXIDE EXCHANGES IN THE LIVER

肝脏中的二氧化碳交换

• 批准号: 3237176
• 负责人: SUSANNA J DODGSON
• 金额: $ 14.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237176
• 关键词: acetazolamide; acid base balance; bicarbonates; carbon dioxide; carbonate dehydratase; carbonic anhydrase inhibitors; citrulline; diet; enzyme induction /repression; enzyme substrate; gluconeogenesis; growth /development; guinea pigs; kidney metabolism; laboratory rabbit; laboratory rat; liver circulation; liver metabolism; mass spectrometry; membrane permeability; mitochondria; nitrogen metabolism; nutrition related tag; ornithine; stop flow technique; sulfonamides; urea cycle

The aim of this proposal is to further study the nature of the unique liver mitochondria carbonic anhydrase, CAmit. We have found that incubating intact mitochondria with substrates for citrullinogenesis plus the sulfonamide carbonic anhydrase inhibitor acetazolamide results in decreased citrulline production. Our hypothesis is that the function of CAmit is to provide the substrate HCO3- for the first urea cycle enzyme, the mitochondrially located carbamyl phosphate synthetase I. We will determine if there are any other effects of the sulfonamides on the mitochondria. We have also found that incubating intact hepatocytes with substrates for ureagenesis plus sulfonamide carbonic anhydrase inhibitors results in decreased urea production, but that greater than 1000-fold the concentration is needed compared with inhibition of citrullinogenesis. We will determine what it is in the hepatocyte that binds on to sulfonamides. We will determine whether CAmit activity is increased by the same factors which increase if CAmit can be inhibited in the whole body, and what this effect would be.

该提议的目的是进一步研究 独特的肝线粒体碳酸酐酶，CAMIT。 我们有 发现将完整的线粒体与底物孵育 柑橘氨基氨基氨基酶发生加磺酰胺碳酸酐酶抑制剂 乙酰唑胺导致瓜氨酸的产生减少。 我们的 假设是CAMIT的功能是提供 底物HCO3-对于第一个尿素周期酶， 线粒体位于磷酸氨基磷酸盐合成酶I.我们将 确定磺酰胺是否还有其他影响 线粒体。 我们还发现，孵化完整 肝细胞，带有尿素的底物加磺酰胺 碳酸酐酶抑制剂导致尿素降低 生产，但浓度大于1000倍 与抑制柑橘酶发生相比，需要。 我们将 确定它在肝细胞中的结合 磺酰胺。 我们将确定CAMIT活动是否是 增加了相同的因素，如果CAMIT可以增加 全身受到抑制，这种影响将是什么。