AMP deaminase and adenosine deaminase activities in liver and brain regions in acute ammonia intoxication and subacute toxic hepatitis.
Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions.
Kaminsky
Yury
Y
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia. kaminsky@iteb.ru
Kosenko
Elena
E
D000659:AMP Deaminase / Q000378:metabolism*; D000208:Acute Disease; D000227:Adenine Nucleotides / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000641:Ammonia / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D022124:Hyperammonemia / Q000201:enzymology* / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D000641:Ammonia; D000243:Adenosine Deaminase; D000659:AMP Deaminase