THE EFFECT OF DIPEPTIDE STRUCTURE ON DIPEPTIDE AND AMINO-ACID CLEARANCE IN RATS

The kinetics of disappearance from the blood of GlyTyr, TyrArg, AlaTyr , TyrAla, GlnGly, GlyGln, GlnAla, and AlaGln and their constituent ami no acids was assessed in anesthetized (pentabarbitone) Sprague-Dawley rats (n = 5 for each peptide). Catheters were inserted into both inter nal jugular veins. A bolus injection of dipeptide was administered int o one catheter, and rapid blood samples were taken from the other cath eter for measurement of dipeptide and amino acid concentrations. Kinet ic parameters for the disappearance of dipeptides and of the amino aci ds released from;the dipeptides from the blood were calculated using s tandard equations. All dipeptides were cleared rapidly from the blood (clearances ranged from 42.9 +/- 3.28 ml/min/kg body weight for GlyGln to 278 +/- 70.7 for GlnAla, mean +/- SD). Glutaminyl dipeptides with alanine or glycine in the C-terminal position or dipeptides with alani ne in the N-terminal position had the greatest clearance values and th e shortest half-lives (t(1/2)). There were significant differences (P < .001) in the volume of distribution of the dipeptides. Many dipeptid es had volumes of distribution greater than the blood Volume of the an imals. The amino acids released from the dipeptides had a longer t(1/2 ) (P < .001) than their parent dipeptides. The t(1/2) and the weight-c orrected area under the blood concentration-versus-time curve (AUC) of the same amino acid released from different dipeptides differed (P < .05). In conclusion, (1) the clearance of dipeptides from the blood is a function of their structure; (2) the release of amino acids from th e dipeptides is more rapid than their elimination from the blood; and (3) the elimination of amino acids from the blood is a function of the structure of the parent dipeptide. These results are discussed in lig ht of current information on the metabolism of dipeptides and their co nstituent amino acids. Copyright (C) 1994 by W.B. Saunders Company