Response of phenylalanine and leucine kinetics to branched chain-enriched amino acids and insulin in patients with cirrhosis.

Abstract

We tested the effects of branched chain-enriched, aromatic-deficient amino acids with insulin to correct the altered protein turnover as well as phenylalanine (Phe) and leucine (Leu) rate of appearance in compensated cirrhotics and controls. Phe and Leu tracers were infused both before and following intravenous amino acid administration with insulin and euglycemic clamp. In cirrhosis, fasting whole-body protein synthesis and protein degradation were normal; Phe rate of appearance was greater (P<0.05), whereas Leu rate of appearance/Phe rate of appearance ratio was approximately 35% less than in controls (P<0.001). Following the infusion, protein synthesis did not increase (+1% +/ 5% [NS] vs. +21% +/- 5% [P<0.05] in controls); protein degradation was more suppressed, whereas protein balance increased normally. Total Phe rate of appearance (0.91 +/- 0.13 micromol x kg-1 x min-1) and Leu/Phe disposal ratio (3.53 +/- 0.36) were nearly normalized (fasting controls, 0.68 +/- 0.07 micromol x kg-1 x min-1 and 2.87 +/- 0.14 micromol x kg-1 x min-1, respectively; P>0.05). However, Leu/Phe endogenous rate of appearance ration remained approximately 50% less (1.56 +/- 0.31 vs. 2.87 +/- 0.14; P<0.004) than in controls. Following this combined infusion in cirrhosis, net protein deposition increased normally despite a blunted response of protein synthesis. Phe and Leu to Phe peripheral disposal were near normalized; however, the exaggerated endogenous Phe production was not corrected entirely.