Utilization of tyrosine-containing dipeptides and N-acetyl-tyrosine in hepatic failure

Abstract

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 Nacetyl-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 (Cl tot) 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 Cl tot 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 Cl tot 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 (k le) 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 NacTyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of AlaTyr, for the first time, enables a simple rapid nonisotope evalution of tyrosine kinetics for assessement of liver function.