CARBON DIOXIDE EXCHANGES IN THE LIVER

这项建议的目的是进一步研究 独特的肝脏线粒体碳酸酐酶，Camit。我们有 发现将完整的线粒体与底物孵育 瓜氨酸生成加磺胺碳酸酐酶抑制剂 乙酰唑胺导致瓜氨酸产量下降。我们的 假设Camit的功能是提供 底物HCO3-对于第一个尿素循环酶， 线粒体定位的氨基甲酰磷酸合成酶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 具有尿失禁底物的肝细胞加磺胺 碳酸酐酶抑制剂导致尿素减少 生产，但超过1000倍的浓度是 与抑制瓜氨酸生成相比，这是必要的。我们会 确定结合在肝细胞中的是什么 磺胺类药物。我们将确定卡米特活动是否 增加了相同的系数，如果Camit可以 全身的抑制作用，以及这种影响会是什么。

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.