CARBON DIOXIDE EXCHANGES IN THE LIVER

这一建议的目的是进一步研究的性质

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.