Intestinal Transport of Amino Acid Residues of Dipeptides

Abstract

Abstract The flux of the glycine residue of glycyl-l-proline (Gly-Pro) from intestinal lumen into mucosal cell was investigated in rabbit ileum. Measurements of tissue 14C, after 60-s exposure of the mucosal surface to [Gly-14C]Gly-Pro at concentrations from 0.05 to 32 mm, suggest two saturable influx processes, one with a Vmax of 0.59 µmole per cm2 hr and an apparent affinity constant (Kt) of 0.93 mm, and the other with a Vmax of 4.03 µmoles per cm2 hr and a Kt of 56.8 mm. The low Kt process was investigated further. After brief exposure to 0.5 mm [Gly-14C]Gly-Pro, all 14C in the tissue was in the form of free glycine. The influx of [Gly-14C]Gly-Pro (Gly(Gly-Pro) influx) at 0.5 mm Gly-Pro concentration was not inhibited by 20 mm glycine and inhibited only 8% by 20 mm l-proline. Conversely, Gly-Pro (20 mm) did not inhibit the influx of either [3H]glycine (0.5 mm) or [3H]proline (0.5 mm). l-Methionine, l-phenylalanine, and l-leucine all markedly inhibited glycine influx but had little or no effect on Gly(Gly-Pro) influx. In contrast, Met-Pro and Phe-Pro strongly inhibited Gly(Gly-Pro) influx but had little effect on glycine influx. All peptides tested inhibited Gly(Gly-Pro) influx except those which lacked a free NH2-group in the α position. In the case of Leu-Leu, this inhibition was shown to be competitive. Gly(Gly-Pro) influx was dependent on the Na+ concentration in the mucosal medium, although, at a Na+ concentration close to zero, influx was far greater than could be accounted for by passive diffusion. Removal of Na+ inhibited Gly-(Gly-Pro) influx by reducing Vmax, whereas it inhibited glycine influx by increasing Kt. Loading tissues first with 50 mm glycine or Gly-Pro reduced Gly(Gly-Pro) influx, whereas prior loading with 50 mm proline, leucine, or d-glucose did not inhibit. It is concluded that most Gly(Gly-Pro) influx at low Gly-Pro concentrations occurs by a process selective for dipeptides with a free NH2 group in the α position. The process is partially inhibited by a low Na+ concentration in the mucosal medium and also by a high glycine concentration in the mucosal cell.