One common metabolite of nitrogen t

One common metabolite of nitrogen that is formed from many nitrogen-containing com-pounds, and is used as a source of nitrogen for biosynthesis, is ammonia. High levels of ammonia are, however, quite toxic. The reason for this toxicity is shown in Figure 39. Brain appears to be the organ that is sensitive to high levels of ammonia. Brain func-tions almost exclusively on glucose oxidation, with this oxidation occurring via acetyl CoA formation and active Krebs' cycle energy production. For acetyl CoA to be metabolized through the Krebs' cycle, a source of oxaloacetate is essential, and in the brain, this requirement is met by the carboxylation of pyruvate. Brain pyruvate carboxylase is limiting and therefore for efficient Krebs' cycle activity in brain, a considerable recycling of oxaloacetate is necessary. In the presence of high levels of ammonia, the equilibrium for the glutamate dehydrogenase reaction lies in favor of glutamate, which will then lead to the formation of glutamine. Both of these reactions diminish the level of the Krebs' cycle intermediates and oxaloacetate is not regenerated. The brain becomes de-prived of its source of ATP, leading to the symptoms of ammonia toxicity. A further complication is that both glutamine and asparate, which can be readily formed from glutamate, have neurotransmitter functions.