UTILIZATION OF TYROSINE DIPEPTIDES AND ACETYLTYROSINE IN NORMAL AND UREMIC HUMANS

The impact of renal failure on the elimination and hydrolysis of three sources of tyrosine for parenteral nutrition, the dipeptides alanyltyrosine (Ala-Tyr), glycyltyrosine (Gly-Tyr), and N-acetyltyrosine (NAc-Tyr) was investigated in eight patient on regular hemodialysis therapy (HD) and seven healthy controls (CON). In CON, whole body clearance (C(tot)) of Ala-Tyr (3,169 +/- 198 ml/min) was higher than Gly-Tyr (1,781 +/- 184, P < 0.001), and both exceeded NAc-Tyr (284 +/- 24, P < 0.001). In HD, C(tot) of Ala-Tyr was not different from CON, but C(tot) of Gly-Tyr (858 +/- 73, P < 0.001) and NAc-Tyr (129 +/- 30, P < 0.02) was decreased. The rise in plasma levels of constituent amino acids was higher in Ala-Tyr vs. Gly-Tyr (P < 0.01). In HD, the pattern was similar, although the increase in Tyr was less than in CON. Plasma Tyr did not increase with NAc-Tyr in either group. Urinary loss of peptides was neglible, but 60% of NAc-Tyr infused was excreted by CON. The half-life of peptides incubated in CON and HD plasma was unchanged for Ala-Tyr (12.3 +/- 0.9 vs. 14.6 +/- 1.9 min) and prolonged for Gly-Tyr in HD (101.7 +/- 4.9 vs. 131.3 +/- 12, P < 0.05). Thus renal failure does not impair Ala-Tyr disposal and delays Gly-Tyr utilization. These differential effects on peptide assimilation underscore the importance of peptide structure on metabolism. Both peptides, but not NAc-Tyr, may serve as a nutritional substrate in renal failure patients.