Chronic inhibition of brain protein synthesis after portacaval shunting: A possible pathogenic mechanism in chronic hepatic encephalopathy in the rat

We investigated the effects of chronic portacaval shunting, with or without additional ammonia loading, on brain protein synthesis in unanesthetized rats by continuous intravenous infustion of³H-lysine (10 µmoles per gram, 0.2 µCi/µmole). Lysine was incorporated into forebrain proteins at a rate of 1.6 nanomoles/mg protein per hour in sham-operated controls, but at a rate of only 0.83 nanomoles/mg protein per hour (p < 0.001) in paired rats 6 to 8 weeks after construction of a portacaval shunt. An acute load of ammonium acetate in portacaval-shunted animals further decreased the rate of lysine incorporation into forebrain proteins. Chronic inhibition of protein synthesis may play a role in the pathogenesis of chronic portacaval encephalopathy.