Metabolic fate of isoleucine in a rat model of hepatic encephalopathy and in cultured neural cells exposed to ammonia

摘要: Hepatic encephalopathy is a severe neuropathological condition arising secondary to liver failure. The pathogenesis not well understood; however, hyperammonemia considered be one causative factor. Hyperammonemia has been suggested inhibit tricarboxylic acid (TCA) cycle activity, thus affecting energy metabolism. Furthermore, it that catabolism of the branched-chain amino isoleucine may help curb effect by by-passing TCA block as providing carbon skeleton for glutamate and glutamine synthesis fixating ammonia. Here we present novel results describing [U-13C]isoleucine metabolism in muscle brain analyzed mass spectrometry bile duct ligated rats, model chronic hepatic encephalopathy, discuss them relation previously published from neural cell cultures. tissue was about five times higher than which, turn, lower corresponding However, supported isoleucine. In rat brain, differential labeling patterns suggest primarily metabolized astrocytic compartment which accordance with previous findings Lastly, glutamate, aspartate GABA do any significant inhibition ammonia activity corresponds Branched-chain acids including are used treating shed light on possible mechanism involved. low turn-over suggests this does serve role metabolites pertinent function hence formation necessary subsequent fixation hyperammonemia. could, contribute likely value treatment encephalopathy.