In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid-enriched diets.
Low plasma levels of branched-chain amino acids, leucine, isoleucine, and valine are postulated to play an etiologic role in hepatic encephalopathy. Supplementation is advocated to reverse encephalopathy and improve nutritional status and survival. We measured in vivo leucine metabolism in normal individuals (n = 5) and in two groups of patients with cirrhosis (n = 8) with a primed continuous infusion of L-[15N, 1-13C] leucine to quantitate the following parameters of leucine metabolism: nitrogen and carbon fluxes, oxidation, contribution to protein synthesis, breakdown of endogenous protein to leucine, deamination and reamination to/from ketoisocaproate. Studies were performed in the fasting and fed states with a conventional enteral diet (Propac) and a branched chain-enriched diet (one third Propac plus two thirds Hepatic-Aid). In vivo leucine metabolism was similar in the fasting and fed states in normal individuals in patients with cirrhosis and with both diets when studied at a protein intake of 0.6 gm/kg ideal body weight/day. When fed these diets, oxidation increased (p less than 0.05) and breakdown decreased (p less than 0.05). The Hepatic-Aid diet increased (p less than 0.05) nitrogen and carbon fluxes significantly more than did the standard diet. Four additional patients with cirrhosis on a diet with more protein were studied (0.75 gm/kg ideal body weight/day). Carbon and nitrogen fluxes, oxidation, synthesis, and deamination were increased (p less than 0.05) when patients with cirrhosis were fed the Propac diet compared with those who fasted. The Hepatic-Aid diet further increased (p less than 0.05) all parameters except synthesis and did not decrease protein breakdown. These data show that patients with cirrhosis metabolize leucine in vivo in a manner identical to that of normal subjects and that leucine-enriched formulas increase oxidation to CO2 without improving protein synthesis.
D000328:Adult; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D004044:Dietary Proteins / Q000008:administration & dosage*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins; D007930:Leucine