Effect of hyperammonemia on leucine and protein metabolism in rats

The cause of muscle wasting and decreased plasma levels of branched chain a mino acids (BCAA), valine, leucine, and isoleucine in liver cirrhosis is ob scure. Here we have evaluated the effect of hyperammonemia. Rats were infus ed with either an ammonium acetate/bicarbonate mixture, a sodium acetate/bi carbonate mixture, or saline for 320 minutes. The parameters of leucine and protein metabolism were evaluated in the whole body and in several tissues using a primed constant intravenous infusion of L-[1-C-14]leucine. Ammoniu m infusion caused an increase in ammonia and glutamine levels in plasma, a decrease in BCAA and alanine in plasma and skeletal muscle, a significant d ecrease in whole-body proteolysis and protein synthesis, and an increase in leucine oxidized fraction. A significant decrease in protein synthesis aft er ammonium infusion was observed in skeletal muscle while a nonsignificant effect was observed in liver, gut, heart, spleen, and kidneys. We conclude that the decrease in plasma BCAA after ammonia infusion is associated with decreased proteolysis and increased leucine oxidized fraction. Copyright ( C) 2000 by W.B. Saunders Company.