title: An active mechanism for completion of the final stage of protein degradation in the liver, lysosomal transport of dipeptides.
abstract: 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 preparation of liver lysosomes using Gly-3H-Gln as the probe. The results 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) there was a coupling between transport of protons and Gly-Gln with a stoichiometry of 1:1; (d) the presence of both acidic pH and membrane potential was necessary for uphill transport of Gly-Gln; (e) a single transporter with a Km of 4.67 mM mediated the uptake of Gly-Gln; and (f) Gly-Gln uptake was inhibited by dipeptides and tripeptides but not by amino acids. The results suggest the presence of a low affinity proton-coupled oligopeptide transporter in the liver lysosomal membrane which mediates transfer of dipeptides from a region of low dipeptidase activity (intralysosome) to a region of high dipeptidase activity (cytosol). In this manner, the transporter provides an active mechanism for completion of the final stage of protein degradation.
authors.affiliation: Clinical Nutrition Research Unit, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: M
authors.initials: M
authors.lastname: Thamotharan
authors.forename: Y B
authors.initials: YB
authors.lastname: Lombardo
authors.forename: S Z
authors.initials: SZ
authors.lastname: Bawani
authors.forename: S A
authors.initials: SA
authors.lastname: Adibi
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002458:Cell Fractionation; D004151:Dipeptides / Q000378:metabolism* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology; D014316:Tritium
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D004151:Dipeptides; D011506:Proteins; D014316:Tritium; C039788:glycylglutamine; D012964:Sodium