CARBON DIOXIDE EXCHANGES IN THE LIVER

肝脏中的二氧化碳交换

• 批准号: 3237174
• 负责人: SUSANNA J DODGSON
• 金额: $ 13.23万
• 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/3237174
• 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.

这一建议的目的是进一步研究的性质