Mechanism of Hepatic Assimilation of Dipeptides

To investigate dipeptide assimilation by the liver, a series of interrelated experiments were performed in rats. Partial hepatectomy prolonged the plasma halflife (min) of Gly-Ala (3.42 f 0.22 uersus 4.90 f 0.35, p < 0.05) but had no significant effect on plasma halflife of Gly-Leu, Gly-Pro, or Gly-Sar. We then investigated the rate of disappearance (pmol*(g liver. h)”) of the above four dipeptides (initial concentration = 1 mM) from the medium during isolated liver perfusion. The order of dipeptide disappearance was: Gly-Leu (8.75 f 0.65) > Gly-Ala (3.36 f 0.46) > Gly-Pro (1.29 2 0.54) > Gly-Sar (0.35 k 0.12). This order of dipeptide disappearance corresponded exactly to the order of the rates of glycine accumulation in the medium during liver perfusion with the four dipeptides. Addition of glucagon had no effect on the disappearance rate of Gly-Ala from the medium, but reduced accumulation rates of glycine (3.39 f 0.30 versus 1.42 f 30, p < 0.01) and alanine (4.42 f 0.66 uersus 1.35 f 0.39, p < 0.01). Finally, we found that hydrolysis by the liver plasma membranes and/or perfusion medium accounted for disappearance of dipeptides. In conclusion, the liver does not appear to have a transport system for dipeptides, but assimilates dipeptides by extracellular hydrolysis. Hydrolysis is achieved by enzymes either located on the plasma membranes or released from the cytosol. The amino acid residues released as the result of dipeptide hydrolysis are then taken up by the liver.