EFFECTS OF ORNITHINE AMINOTRANSFERASE INACTIVATION BY 5-FLUOROMETHYLORNITHINE IN RATS FOLLOWING PORTACAVAL ANASTOMOSIS

5-Fluoromethylornithine (5FMOrn) is a selective inactivator of ornithi ne aminotransferase. Administration of this compound to rodents causes a prominent increase of tissue ornithine concentrations, and prevents the neurological consequences of acute ammonia intoxication. However, long-term treatment with 5FMOrn of rats with portacaval shunts did no t result in decreased circulating ammonia concentrations, nor did it p revent other pathologic manifestations of shunting. The sensitivity to ammonia intoxication of rats with portacaval shunts was also unaffect ed by pretreatment with 5FMOrn, although liver ornithine concentration s were significantly elevated; specific activities of urea cycle enzym es were slightly higher in portacaval shunted compared to sham-operate d controls following 5-FMOrn treatment. Administration of 5FMOrn drama tically elevated urinary excretion of several amino acids in rats with portacaval shunts, but not in sham-operated animals, suggesting that the reabsorption of amino acids from the glomerular filtrate may be im paired in shunted rats. These results suggest that, in contrast to acu te hyperammonemic syndromes, 5-FMOrn may be of limited therapeutic val ue in chronic hyperammonemia syndromes in which there is significant p ortal-systemic shunting.