Abnormalities in branched-chain amino acid metabolism in cirrhosis: influence of hormonal and nutritional factors and directions for future research.
Plasma branched-chain amino acid (BCAA) levels are decreased in patients with liver cirrhosis, owing to an increase in BCAA tissue uptake and/or catabolism and a decrease in BCAA production from proteins. Non-specific factors such as malnutrition worsen this picture. Studies of BCAA fluxes and protein turnover in cirrhotic patients have given conflicting results due to patient heterogeneity, differences in method and bias in the expression of results. In well compensated cirrhosis, muscle wasting is moderate and probably due more to decreased protein synthesis than to increased protein catabolism. Hyperinsulinemia has been suggested as the main cause of decreased BCAA levels, by increasing BCAA uptake in muscle and additionally in adipose tissue. However, as depletion of fat stores is frequent in cirrhosis, this effect is certainly quantitatively weak. Also, there is no correlation between state of hyperinsulinemia and decrease in BCAA levels. An effect of cytokines (IL1 and TNF) on muscle BCAA catabolism is a possibility. Until recently, the contribution of the liver to abnormal BCAA metabolism has been underestimated. In cirrhotic liver an increase in liver transamination of branched-chain keto acids (BCKAs) has been suggested and may result from inhibition of liver BCKA dehydrogenase. A modification of protein turnover in cirrhotic liver must be also considered. Lastly, the contribution of non-hepatocyte liver cells, which are activated in cirrhosis, remains to be assessed.
Blonde-Cynober
F
F
Biochem Laboratory Emile Roux Hospital, INSERM U402, CHU St Antoine, Paris, France.
Aussel
C
C
Cynober
L
L
D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007930:Leucine / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009752:Nutritional Status; D011506:Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000597:Amino Acids, Branched-Chain; D007375:Interleukin-1; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D007930:Leucine