Clearance of dipeptides from plasma: role of kidney and intestine

The metabolic fate of glycylglycine and glycyl-L-leucine administered intravenously to rats, and the processes involved in the clearance of these dipeptides from plasma, have been studied. The dipeptides disappeared rapidly from plasma without being lost in the urine or accumulating in body tissues, but concentrations of glycine or leucine, or both, increased markedly in plasma and body tissues. All tissues except blood had considerable hydrolase activity against Gly-Gly and Gly-Leu, with kidney and intestine being far more active than liver and muscle in this regard. When uptake of glycylsarcosine, which is resistant to hydrolysis, was investigated after intravenous injection, its disappearance from plasma was slower than that of Gly-Gly, but Gly-Sar accumulated in all tissues examined (liver, muscle, renal cortex and intestinal mucosa). Its concentration in the renal cortex far exceeded (over 14-fold) that in other tissues, and a considerable portion of the injected Gly-Sar dose appeared in the urine. Bilateral nephrectomy did not have a remarkable effect on the plasma half-life of Gly-Leu or Gly-Gly but markedly prolonged that of Gly-Sar. Nephrectomy also allowed greater tissue accumulation of Gly-Sar and recovery of Gly-Gly and Gly-Leu from tissues. The plasma half-life of Gly-Gly was also not remarkably affected by total enterectomy. These studies suggest that (a) clearance of dipeptides from plasma is chiefly a function of tissue uptake and hydrolysis, and (b) among dipeptides, those resistant to hydrolysis depend to a great extent on kidneys for their clearance from plasma.