title: Effects of acute hyperammonemia in vivo on oxidative metabolism in nonsynaptic rat brain mitochondria.
abstract: The effects of hyperammonemia induced in vivo by injecting rats with ammonium acetate on oxidative phosphorylation, malate-aspartate shuttle, some related enzyme activities and metabolite levels in brain mitochondria were studied ex vivo. Rats were found to be either ammonia-sensitive (showing convulsions) or ammonia-resistant (without convulsions) after intraperitoneal injection of ammonium acetate (7 mmol/kg). Ammonium acetate administration to ammonia-sensitive rats led to inhibition of State 3 rates of brain mitochondria utilizing pyruvate, glutamate, isocitrate, and succinate as substrates and to decreased respiratory control index. In brain mitochondria isolated from ammonia-resistant animals, the ammonia-induced effect on such State 3 rates was not observed. In brain mitochondria from hyperammonemic rats without convulsions, a small increase in the activity of malate dehydrogenase was observed; glutamate dehydrogenase, succinate dehydrogenase, and aspartate aminotransferase were not affected. In brain mitochondria from rats with ammonia-induced convulsions, the activities of malate dehydrogenase and succinate dehydrogenase were reduced significantly. Ammonium acetate injection to rats was associated with a 5-fold increase in the brain mitochondrial ammonium ion content and a decrease (ca. 50%) in brain mitochondrial glutamate and aspartate; brain mitochondrial malate and 2-oxoglutarate levels remained unchanged. The rate of the malate-aspartate shuttle in brain mitochondria of hyperammonemic rats was decreased by 20% as compared to corresponding rate in control rats. We conclude that acute administration of ammonium acetate induces serious disturbances in the electron-transport chain, interferences of the malate-aspartate shuttle, alterations of the levels of shuttle intermediates and inhibition of the activities of malate and succinate dehydrogenases in brain mitochondria.
authors.affiliation: Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.
authors.forename: E
authors.initials: E
authors.lastname: Kosenko
authors.forename: V
authors.initials: V
authors.lastname: Felipo
authors.forename: C
authors.initials: C
authors.lastname: Montoliu
authors.forename: S
authors.initials: S
authors.lastname: Grisolía
authors.forename: Y
authors.initials: Y
authors.lastname: Kaminsky
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000641:Ammonia / Q000097:blood*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D000085:Acetates; D008293:Malates; D001224:Aspartic Acid; D000641:Ammonia; D008291:Malate Dehydrogenase; D013385:Succinate Dehydrogenase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; C018824:ammonium acetate