title: Mitochondrial dysfunction in acute hyperammonemia.
abstract: Acute hyperammonemia resulting from congenital urea cycle disorders, Reye syndrome or acute liver failure results in severe neuronal dysfunction, seizures and death. Increasing evidence suggests that acute hyperammonemia results in alterations of mitochondrial and cellular energy function resulting from ammonia-induced inhibition of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase and by activation of the NMDA receptor. Antagonists of this receptor and NOS inhibitors prevent acute ammonia-induced seizures and mortality and prevent acute ammonia-induced changes in mitochondrial calcium homeostasis and cellular energy metabolism. Acute hyperammonemia also results in decreased activities of free radical scavenging enzymes and again, free radical formation due to ammonia exposure is prevented by either NMDA receptor antagonists or NOS inhibitors. Acute hyperammonemia also results in activation of "peripheral-type" benzodiazepine receptors and monoamine oxidase-B, enzymes which are localized on the mitochondrial membranes of astrocytes in the CNS. Activation of these receptors results in mitochondrial swelling and in increased degradation of monoamines, respectively. Alterations of mitochondrial function could contribute to the neuronal dysfunction characteristic of acute hyperammonemic syndromes.
authors.affiliation: Instituto Investigaciones Citologicas de la Fundacion Valenciana de Investigaciones Biomedicas, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000208:Acute Disease; D000818:Animals; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D009420:Nervous System / Q000473:pathology; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate