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 amino acids was assessed in anesthetized (pentabarbitone) Sprague-Dawley rats (n = 5 for each peptide). Catheters were inserted into both internal jugular veins. A bolus injection of dipeptide was administered into one catheter, and rapid blood samples were taken from the other catheter for measurement of dipeptide and amino acid concentrations. Kinetic parameters for the disappearance of dipeptides and of the amino acids released from the dipeptides from the blood were calculated using standard 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 alanine in the N-terminal position had the greatest clearance values and the shortest half-lives (t1/2). There were significant differences (P < .001) in the volume of distribution of the dipeptides. Many dipeptides had volumes of distribution greater than the blood volume of the animals. The amino acids released from the dipeptides had a longer t1/2 (P < .001) than their parent dipeptides. The t1/2 and the weight-corrected area under the blood concentration-versus-time curve (AUC) of the same amino acid released from different dipeptides differed (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Kee
A J
AJ
University of Sydney, NSW, Australia.
Smith
R C
RC
Gross
A S
AS
Madsen
D C
DC
Rowe
B
B
D000596:Amino Acids / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010288:Parenteral Nutrition; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D004151:Dipeptides