Free amino acids in plasma and skeletal muscle of patients with liver cirrhosis

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Abstract
Free amino acids were measured under postabsorptive conditions in plasma and intracellular water of skeletal muscle obtained by needle biopsy in nine healthy controls and 14 subjects suffering from clinically stable liver cirrhosis. The aromatic amino acids phenylalanine and tyrosine in cirrhotics were elevated to the same extent in plasma and in muscle water. Branched-chain amino acids were uniformly reduced in plasma, but in muscle water only valine was significantly lower (222 ± 92 μmoles per kg intracellular water vs. 368 ± 82, p < 0.001), while isoleucine (142 ± 63 vs. 103 ± 30), leucine (223 ± 88 vs. 226 ± 36) and branched-chain amino acids as a whole (589 ± 186 vs. 681 ± 88) were normal or elevated with an increased muscle:plasma ratio (3.12 ± 2.03 vs. 1.41 ± 0.37, p < 0.05 for isoleucine; 3.00 ± 1.28 vs. 1.85 ± 0.27, p < 0.025 for leucine; 2.24 ± 0.64 vs. 1.69 ± 0.13, p < 0.05 for total branched-chain amino acids. Our data show that, in cirrhosis, plasma concentrations of branched-chain amino acids do not reflect their levels in muscle cellular water; only the intracellular pool of valine is severely depleted. This suggests that higher amounts of valine supplementation may be useful in nutritional treatment of liver cirrhosis. The elevated muscle:plasma gradients for branched-chain amino acids may result from abnormalities in their transport through muscle-plasma membrane. These abnormalities may contribute to the reduced basal rate of net muscle branched-chain amino acid release and, in turn, to the low fasting plasma levels of these amino acids in liver cirrhosis. The altered intra- and extracellular distribution of branched-chain amino acids should also be taken into account when interpreting metabolic studies on turnover or clearance of branched-chain amino acids in cirrhotic patients.