M. Thamotharan et al., AN ACTIVE MECHANISM FOR COMPLETION OF THE FINAL STAGE OF PROTEIN-DEGRADATION IN THE LIVER, LYSOSOMAL TRANSPORT OF DIPEPTIDES, The Journal of biological chemistry, 272(18), 1997, pp. 11786-11790
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.