AN ACTIVE MECHANISM FOR COMPLETION OF THE FINAL STAGE OF PROTEIN-DEGRADATION IN THE LIVER, LYSOSOMAL TRANSPORT OF DIPEPTIDES

Accumulation of products of proteolysis (e.g. dipeptides) in lysosomes may have pathological consequences. In the present experiment we have investigated the existence of a dipeptide transporter in a membrane p reparation of liver lysosomes using Gly-H-3-Gln as the probe. The resu lts showed that (a) there was transport of Gly-Gln into an osmotically reactive space inside the lysosomal membrane vesicles; (b) transport was stimulated by acidification (pH 5.0) of the external medium; (c) t here was a coupling between transport of protons and Gly-Gln with a st oichiometry of 1:1; (d) the presence of both acidic pH and membrane po tential was necessary for uphill transport of Gly-Gln; (d) a single tr ansporter with a K-m of 4.67 mM mediated the uptake of Gly-Gln; and (f ) Gly-Gln uptake was inhibited by dipeptides and tripeptides but not b y amino acids. The results suggest the presence of a low affinity prot on-coupled oligopeptide transporter in the liver lysosomal membrane wh ich mediates transfer of dipeptides from a region of low dipeptidase a ctivity (intralysosome) to a region of high dipeptidase activity (cyto sol). In this manner, the transporter provides an active mechanism for completion of the final stage of protein degradation.