Saul R, Molyneux R J, Elbein A D
Arch Biochem Biophys. 1984 May 1;230(2):668-75. doi: 10.1016/0003-9861(84)90448-x.
Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is an indolizidine alkaloid that was isolated from the Australian plant, Castanospermum australe. This alkaloid was found to be a potent inhibitor of lysosomal alpha- and beta-glucosidases. In this report, the mechanism of inhibition of amyloglucosidase (an exo-1,4-alpha-glucosidase) and almond emulsin beta-glucosidase was examined. Castanospermine proved to be a competitive inhibitor of amyloglucosidase at both pH 4.5 and 6.0 when assayed with the p-nitrophenyl-alpha-D-glucoside. It was also a competitive inhibitor of almond emulsin beta-glucosidase at pH 6.5, but in this case previous studies had shown that inhibition was of the mixed type at pH 4.5 to 5.0. Th pH of the incubation mixture had a marked effect on the inhibition. Thus, in all cases, castanospermine was a much better inhibitor at pH 6.0 to 6.5 than it was at lower pH values. The pK for castanospermine was found to be 6.09, indicating that the alkaloid was probably more active in the unprotonated form. This was also suggested by the fact that the N-oxide of castanospermine, while still a competitive inhibitor, was 50 to 100 times less active than was castanospermine, and its activity was not markedly altered by pH. These results probably explain why castanospermine is a good inhibitor of the glycoprotein processing enzyme, glucosidase I, since this is a neutral enzyme.
栗精胺（1,6,7,8 - 四羟基八氢中氮茚）是一种从澳大利亚植物栗豆树（Castanospermum australe）中分离出的中氮茚生物碱。该生物碱被发现是溶酶体α - 和β - 葡萄糖苷酶的有效抑制剂。在本报告中，研究了其对淀粉葡萄糖苷酶（一种外切1,4 - α - 葡萄糖苷酶）和苦杏仁酶β - 葡萄糖苷酶的抑制机制。当用对硝基苯基 - α - D - 葡萄糖苷进行测定时，栗精胺在pH 4.5和6.0时均被证明是淀粉葡萄糖苷酶的竞争性抑制剂。在pH 6.5时，它也是苦杏仁酶β - 葡萄糖苷酶的竞争性抑制剂，但在这种情况下，先前的研究表明在pH 4.5至5.0时抑制作用为混合型。孵育混合物的pH对抑制作用有显著影响。因此，在所有情况下，栗精胺在pH 6.0至6.5时比在较低pH值时是更好的抑制剂。发现栗精胺的pK为6.09，表明该生物碱可能以未质子化形式更具活性。栗精胺的N - 氧化物虽然仍是竞争性抑制剂，但其活性比栗精胺低50至100倍，并且其活性不受pH的显著影响，这一事实也表明了这一点。这些结果可能解释了为什么栗精胺是糖蛋白加工酶葡糖苷酶I的良好抑制剂，因为这是一种中性酶。
