Formation of ammonium ion in the cerebrum in fluoroacetate poisoning.

DMINISTRATION Of a fluoroacetate iS A known to bring about an inhibition of citrate oxidation, thus blocking the tricarboxylic acid cycle and resulting in the accumulation of citrate in various tissues in viva (I). Hence it is pertinent to inquire concerning the source or sources of the J-carbon precursors of the accumulating citrate. One obvious possibility is that an amino acid such as glutamic or aspartic could enter the cycle after removal of the amino group. In such a case the nitrogen might appear as ammonium ion, it might combine with glutamic acid to form glutamine, or it might be transferred to some available keto acid by transamination. Brain tissue is known to contain a considerable quantity of free glutamic acid (2). Fluoroacetate poisoning is characterized by violent epileptiform seizures in some species (3). It is known that convulsions can also be induced by injection of large doses of ammonium salts (4, 5), and that formation of ammonium ion occurs in the brain of the rat on electrical stimulation and during seizures induced by picrotoxin or pentamethylentetrazol (6, 7). Richter and Dawson (6) suggested that the ammonium ion might be the cause of the increased irritability manifested by the convulsions. These considerations prompted a study of ammonium ion and glutamine in the cerebrum during the course of fluoroacetate poisoning in dogs.