Ni qiu de nai an ji zhi | Mechanisms of ammonia tolerance in the oriental weatherloach, misgurnus anguillicaudatus | 泥鰍的耐氨機制

Ammonia is a toxicant that is continuously being produced by all animals. Certain fish species have to deal with, in addition to endogenous ammonia, occasional high environmental ammonia. Different species utilize different strategies in dealing with the problem of ammonia toxicity. Using the oriental weatherloach as a model, four novel mechanisms have been discovered. The weatherloach was found to be able to lower the pH of its ambient water. They do so through carbon dioxide production. Proton excretion does not significantly contribute to the process. By carrying out environmental acidification, the amount of NH3, which readily penetrates membranes, is lowered so that less ammonia will enter the fish. Mitochondrial lactate dehydrogenase was detected in the liver of the weatherloach. The presence of this enzyme can solve the two potential problems associated with detoxification of ammonia to glutamine: 1) Krebs cycle substrate depletion and 2) intramitochondrial redox imbalance. Uncoupling protein 2 (UCP2) in the liver mitochondria was also found to be upregulated during ammonia exposure. UCP2 acts as a proton transporter in the mitochondrial inner membrane and allow back flux of proton into the matrix. By doing so, it regulates mitochondrial membrane potential and, thus, prevents excessive reactive oxygen species (ROS) production associated with hyperammonemia. The background K+ channels in the cardiac myocytes were found to have low permeability to NH4 +. This low NH4 + permeability renders the cardiac cells less susceptible to ammonia-induced depolarization. Postprandial surge in blood ammonia levels can, therefore, be tolerated. It is predicted that the background K+ channels in the brain cells also have low NH4 + permeability. This will explain the functionality of the nervous system during hyperammonemia.

Thesis (Ph.D.)--City University of Hong Kong, 2005

Includes bibliographical references (leaves 148-166)