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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/G598    most recent 00355.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tessari, P. Articles by Orlando, R. PubMed PubMed Citation Articles by Tessari, P. Articles by Orlando, R.

LIVER AND BILIARY TRACT

Phenylalanine and tyrosine kinetics in compensated liver cirrhosis: effects of meal ingestion

¹Department of Clinical and Experimental Medicine, Chair of Metabolism; and ²Internal Medicine, University of Padova, Italy

Submitted 7 August 2007 ; accepted in final form 10 July 2008

We explored the mechanism(s) of increased aromatic amino acids concentrations in liver cirrhosis using phenylalanine (Phe) and tyrosine (Tyr) isotope infusions in male patients with compensated cirrhosis (five in Child Class A, three in B) and in eight matched healthy controls, in both postabsorptive and fed states. After a baseline period, a standard liquid mixed meal was fed continuously over 4 h. Both a "plasma" and an intracellular model were employed. In the patients, steady-state Phe and Tyr concentrations were 30–50% greater, and rates of Phe appearance (Ra) (plasma model), Tyr Ra, and Phe hydroxylation (Hy; both models) were 25 to >100% greater than in controls in both states. Meal ingestion increased (P < 0.05 or less vs. basal) Phe and Tyr concentrations, Phe and Tyr Ra, Phe Hy, and % Tyr Ra not deriving from Hy in both groups. Hy and Tyr Ra remained >50% greater (P < 0.04 to P < 0.01) in patients, whereas Phe Ra was more modestly increased. Phe utilization for protein synthesis increased similarly in both groups. Tyr clearance was normal, whereas Phe clearance tended to be lower (P = 0.09, intracellular model) in the patients. In summary, in compensated liver cirrhosis studied under fasted and fed states, 1) Tyr Ra is increased; 2) Phe Hy and Phe Ra (plasma model) are increased; 3) Tyr clearance is normal; and 4) Phe clearance is slightly decreased. In conclusion, in cirrhosis increased total tyrosine Ra and hydroxylation contribute to fasting and postmeal hypertyrosinemia, whereas the mechanism(s) responsible for the hyperphenylalaninemia may include both increased production and decreased disposal.

compensated liver cirrhosis; mixed meal; tyrosine hydroxylation; stable isotopes