Bird S J, Lloyd J B
Department of Biological Sciences, Keele University, Staffordshire, U.K.
Cell Biochem Funct. 1995 Jun;13(2):79-83. doi: 10.1002/cbf.290130203.
Low concentrations of some neutral dipeptides, such as L-Ala-L-Ala, rapidly 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 challenged by testing several pairs of dipeptides available in both D- and L-forms and a range of dipeptides whose susceptibility to lysosomal dipeptidase activity is known. A good correlation was found between the lytic ability of dipeptides and their capacity to cross the lysosome membrane and be hydrolysed by lysosomal dipeptidase. The osmotic-imbalance hypothesis is critically evaluated in the light of the results and of recent information concerning the carrier-mediated transport of amino acids and dipeptides across the lysosome membrane. It is concluded that intralysosomal generation of amino acids remains the most plausible explanation of the lytic activity of dipeptides, and that the dipeptide porter(s) in the lysosome membrane must have higher Km than the amino acid porters.
低浓度的某些中性二肽，如L-丙氨酰-L-丙氨酸，能迅速破坏大鼠肝脏溶酶体。这种现象被归因于溶酶体二肽酶活性在溶酶体内产生氨基酸所导致的渗透失衡。通过测试几对D型和L型均可获得的二肽以及一系列已知对溶酶体二肽酶活性敏感的二肽，这一假设受到了挑战。发现二肽的裂解能力与其穿过溶酶体膜并被溶酶体二肽酶水解的能力之间存在良好的相关性。根据这些结果以及有关氨基酸和二肽通过溶酶体膜的载体介导转运的最新信息，对渗透失衡假说进行了严格评估。得出的结论是，溶酶体内氨基酸的产生仍然是二肽裂解活性最合理的解释，并且溶酶体膜中的二肽转运体的Km值必定高于氨基酸转运体。
