The aim of this study was to evaluate the effect of acute uremia on changes in leucine and protein metabolism in the whole body and in hepatic tissue. Acute renal insufficiency was induced by bilateral nephrectomy (BNX). Twenty-four hours later, parameters of protein and amino acid metabolism were evaluated in the whole body using primed constant intravenous infusion of L-[1-14C]leucine, and in isolated perfused liver (IPL) using cx-keto[1-14C]isocaproate. The control group consisted of sham-operated rats. BNX induced a marked decrease in proteolysis, protein synthesis, leucine oxidized fraction and leucine clearance. The decrease in protein synthesis was higher than in proteolysis. A significant drop in protein synthesis was observed in muscle, gut, heart and spleen. The study with IPL in BNX animals showed decreased oxidation of ketoisocaproic acid and higher concentrations of the branched-chain amino acids (BCAA) leucine, isoleucine and valine in perfusion solution. We conclude that the cause of rapid depletion of body proteins after BNX is a greater decrease in protein synthesis than in proteolysis associated with an increase in leucine oxidized fraction. The data obtained in the IPL model indicate that BNX causes metabolic changes that enable resynthesis of BCAA from corresponding branched-chain keto acids in liver.

Department of Physiology Charles University School of Medicine Hradec Králové Czech Republic

Muscle wasting in animal models of severe illness

Acute effects of acidosis on protein and amino acid metabolism in perfused rat liver