BACKGROUND/AIMS: This study aimed to investigate the pathogenesis of reduced plasma levels of branched-chain amino acids leucine, isoleucine and valine in cirrhosis. METHODS: Cirrhosis was induced by intragastric administration of 36 doses of carbon tetrachloride in olive oil over a period of 12 weeks. Rats treated with oil alone served as controls. The rates of leucine turnover, clearance, oxidation and incorporation into proteins were evaluated using [1-14C]leucine, [4,5-3H]leucine and alpha-keto[1-14C]isocaproate 3 days after the last intragastric treatment in vivo and in the isolated perfused liver. RESULTS: In animals with cirrhosis we observed a profound fall in plasma branched-chain amino acid levels and significant decreases in leucine turnover, oxidation and incorporation into tissue proteins. A more pronounced fall in leucine incorporation in proteins resulted in a significant increase in the oxidized leucine fraction in rats with cirrhosis as compared to controls. Leucine clearance was higher in the cirrhosis group. Concomitant to the fall of whole body leucine turnover, decreases of leucine incorporation into protein and of ketoisocaproic acid decarboxylation were observed in the isolated perfused liver of rats with cirrhosis. However, leucine oxidation was increased compared with control rats. CONCLUSIONS: Our results indicate that the predominant mechanism of the decrease in plasma leucine levels in rats with cirrhosis is an increase in the oxidized leucine fraction associated with a decrease in leucine turnover. An increase in leucine oxidation in the cirrhotic liver is one of the mechanisms involved.

Charles University School of Medicine Department of Physiology Prague Czech Republic

References provided by Crossref.org

Muscle Amino Acid and Adenine Nucleotide Metabolism during Exercise and in Liver Cirrhosis: Speculations on How to Reduce the Harmful Effects of Ammonia

The role of skeletal muscle in the pathogenesis of altered concentrations of branched-chain amino acids (valine, leucine, and isoleucine) in liver cirrhosis, diabetes, and other diseases

Muscle wasting and branched-chain amino acid, alpha-ketoglutarate, and ATP depletion in a rat model of liver cirrhosis

Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions

Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-therapeutic perspectives

Muscle wasting in animal models of severe illness