MECHANISM OF LYSOSOME RUPTURE BY DIPEPTIDES

Low concentrations of some neutral dipeptides, such as L-Ala-L-Ala, ra pidly disrupt rat liver lysosomes. The phenomenon has been attributed to an osmotic imbalance generated by the production of amino acids in the lysosome by lysosomal dipeptidase activity. This hypothesis is cha llenged by testing several pairs of dipeptides available in both D- an d L-forms and a range of dipeptides whose susceptibility to lysosomal dipeptidase activity is known. A good correlation was found between th e lytic ability of dipeptides and their capacity to cross the lysosome membrane and be hydrolysed by lysosomal dipeptidase. The osmotic-imba lance hypothesis is critically evaluated in the light of the results a nd of recent information concerning the carrier-mediated transport of amino acids and dipeptides across the lysosome membrane. It is conclud ed that intralysosomal generation of amino acids remains the most plau sible explanation of the lytic activity of dipeptides, and that the di peptide porter(s) in the lysosome membrane must have higher K-m than t he amino acid porters.