The effect of 1-deoxymannojirimycin on rat liver alpha-mannosidases.

The mannose analogue, 1-deoxymannojirimycin, has been tested for its effect on five alpha-mannosidase activities present in rat liver and shown to be a specific inhibitor of Golgi alpha-mannosidase I at low mumolar concentrations. Golgi alpha-mannosidases I and II were assayed in a highly purified Golgi membrane preparation. Endoplasmic reticulum alpha-mannosidase activity was measured in a rough endoplasmic reticulum detergent extract. A purified soluble alpha-mannosidase activity which we believe is derived from the endoplasmic reticulum during tissue homogenization was also tested. And finally, the lysosomal or acidic alpha-mannosidase was measured in a postnuclear supernatant fraction obtained from rat liver. The results presented here show that 1-deoxymannojirimycin inhibits only Golgi alpha-mannosidase I, which is consistent with its effect on oligosaccharide processing in vivo (Fuhrmann et al. Nature 1984 307:755-758).