Hyperammonemia and hepatic encephalopathy stimulate rat cerebral synaptic mitochondrial glutamate dehydrogenase activity specifically in the direction of glutamate oxidation.
The effects of hepatic encephalopathy (HE) due to thioacetamide (TAA)-induced liver failure and hyperammonemia (HA) produced by repeated i.p. administration of ammonium acetate on the activity of glutamate dehydrogenase (GlDH) in the direction of glutamate (Glu) synthesis from--(GlDH-NADH) or its oxidation to alpha-ketoglutarate (alpha-KG) (GlDH-NAD), respectively, were examined in non-synaptic and synaptic mitochondria from rat cerebral hemispheres. In non-synaptic mitochondria, HE and HA stimulated the GlDH-NADH activity by, respectively, 33% and 49%, but neither condition affected the GlDH-NAD activity. In synaptic mitochondria, HE and HA decreased the GlDH-NADH activity by, respectively, 31% and 28%, but stimulated the GlDH-NAD activity by as much as 90% (HE) and 100% (HA). Kinetic assays revealed that HA increased the Vmax of the synaptic mitochondrial GLDH-NAD by 105%, without affecting the Km for Glu. The stimulation of GlDH-NAD favors the oxidation of synaptic Glu to alpha-KG, and may represent an adaptive response serving to counteract hyperammonemia-induced decrease of cerebral alpha-KG production in other metabolic pathways.
Faff-Michalak
L
L
Department of Neuropathology, Polish Academy of Sciences, Warsaw.
Albrecht
J
J
D000641:Ammonia / Q000097:blood*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000648:ultrastructure; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000201:enzymology*; D007656:Ketoglutaric Acids / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013569:Synapses / Q000201:enzymology*; D013853:Thioacetamide
D005971:Glutamates; D007656:Ketoglutaric Acids; D013853:Thioacetamide; D018698:Glutamic Acid; D000641:Ammonia; D005969:Glutamate Dehydrogenase