CARBON DIOXIDE EXCHANGES IN THE LIVER

肝脏中的二氧化碳交换

• 批准号: 3237175
• 负责人: SUSANNA J DODGSON
• 金额: $ 13.7万
• 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/3237175
• 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.

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 瓜氨酸生成加上磺酰胺碳酸酐酶抑制剂 乙酰唑胺会导致瓜氨酸产量减少。 我们的 假设 CAmit 的功能是提供 第一个尿素循环酶的底物 HCO3- 位于线粒体的氨甲酰磷酸合成酶 I。我们将 确定磺胺类药物是否有任何其他影响 线粒体。 我们还发现，孵化完好无损 具有尿素生成底物加磺酰胺的肝细胞 碳酸酐酶抑制剂导致尿素减少 产量，但浓度大于 1000 倍 与抑制瓜氨酸生成相比需要。 我们将 确定肝细胞中结合的是什么 磺胺类药物。 我们将确定 CAmit 活动是否 如果 CAmit 可以增加，则增加相同的因素 全身受到抑制，会产生什么影响。