The impact of hepatic dysfunction on the elimination and hydrolysis of three potential
tyrosine sources for
total parenteral nutrition, the
dipeptides L-alanyl-L-tyrosine (
Ala-Tyr) and
glycyl-L-tyrosine (
Gly-Tyr), and N-
acetyl-L-tyrosine (Nac-Tyr) were evaluated in six patients with
hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Cltot) of
Ala-Tyr was higher than of
Gly-Tyr (3,169 +/- 214 vs. 1,780 +/- 199 mL/kg/min, P < .01), and both exceeded clearance of Nac-Tyr (309 +/- 29 mL/kg/min, P > .01). Both
dipeptides were hydrolyzed and released
tyrosine immediately. In
hepatic failure, elimination and hydrolysis of
Ala-Tyr and
Gly-Tyr were comparable to controls, but Cltot of Nac-Tyr was reduced (236 +/- 26 mL/kg/min). Neither in controls nor in patients an increase in plasma
tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cltot of
tyrosine as evaluated after
Ala-Tyr infusion (with the immediate release of
tyrosine) was severely reduced in
hepatic failure (152.7 +/- 38.4 vs. 484.4 +/- 41.4 mL/kg/min, P < .001) and half-life (kle) was retarded from 14.4 +/- 1.4 to 90.2 +/- 32.2 minutes (P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the
dipeptides Ala-Tyr and
Gly-Tyr and the constituent
amino acids are released immediately. Nac-Tyr elimination was not grossly affected by
hepatic failure, but neither in healthy subjects nor in
hepatic failure patients was an increase of
tyrosine seen. Both
dipeptides but not Nac-Tyr may serve as a
tyrosine source in
parenteral nutrition. Moreover, by its rapid hydrolysis, the use of
Ala-Tyr, for the first time, enables a simple rapid nonisotope evaluation of
tyrosine kinetics for assessment of liver function.