CARBON DIOXIDE EXCHANGES IN THE LIVER

肝脏中的二氧化碳交换

• 批准号: 3237170
• 负责人: SUSANNA J DODGSON
• 金额: $ 13.67万
• 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/3237170
• 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; kidney metabolism; 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.

本提案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一起孵育， 瓜氨酸生成加磺酰胺碳酸酐酶抑制剂 乙酰唑胺导致瓜氨酸产生减少。 我们 假设CAmit的功能是提供 第一尿素循环酶的底物HCO 3-， 氨甲酰磷酸合成酶I。 我们将 确定是否有任何其他影响的磺胺类药物， 线粒体 我们还发现， 含尿素生成底物和磺胺的肝细胞 碳酸酐酶抑制剂导致尿素减少 生产，但大于1000倍的浓度是 与抑制瓜氨酸生成相比， 我们将 确定肝细胞中结合到 磺胺 我们将确定CAmit活动是否 增加相同的因素，增加如果CAmit可以 在整个身体中被抑制，以及这种影响会是什么。