Aspartate aminotransferase, malate dehydrogenase, and pyruvate carboxylase activities in rat cerebral synaptic and nonsynaptic mitochondria: effects of in vitro treatment with ammonia, hyperammonemia and hepatic encephalopathy.
The effects of in vitro treatment with ammonium chloride, hepatic encephalopathy (HE) due to thioacetamide (TAA) induced liver failure and chronic hyperammonemia produced by i.p. administration of ammonium acetate on the activity of the two malate-aspartate shuttle enzymes: aspartate aminotransferase (AAT), malate dehydrogenase (MDH), and on the pyruvate carboxylase (PC) activity were examined in synaptic and nonsynaptic mitochondria from rat brain. With regard to the shuttle enzymes the response to ammonium ions in vitro (3mM NH4Cl) was observed in nonsynaptic mitochondria only, and was manifested by a 27% decrease of AAT activity and a 16% decrease in MDH activity. By contrast, both in vivo conditions primarily affected the synaptic mitochondrial enzymes: TAA-induced HE produced a 26% decrease of synaptic mitochondrial AAT and a 50% decrease of synaptic mitochondrial MDH. Hyperammonemia inhibited synaptic mitochondrial AAT by 30% and synaptic mitochondrial MDH by 45%. HE produced no effect at all in nonsynaptic mitochondria while hyperammonemia produced a 30% increase in the AAT activity, but no changes in MDH. All the experimental conditions affected the nonsynaptic mitochondria PC: ammonium chloride in vitro produced a 20% decrease, TAA-induced HE--a 30% decrease, whereas hyperammonemia inhibited the enzyme by 53%. The PC activity in synaptic mitochondria was very low (about 2% of that measured in nonsynaptic mitochondria), which is consistent with the primarily astrocytic localization of the enzyme.
Faff-Michalak
L
L
Department of Neuropathology, Polish Academy of Sciences, Warsaw.
Albrecht
J
J
D000641:Ammonia / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000201:enzymology*; D066298:In Vitro Techniques; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects / Q000201:enzymology*
D009419:Nerve Tissue Proteins; D000641:Ammonia; D008291:Malate Dehydrogenase; D001219:Aspartate Aminotransferases; D011766:Pyruvate Carboxylase