Mannosidase

Inhibition of D-Mannosidases and D-Glucosidases by Swainsonine and Castanospermine, Respectively... 

A case similar to the slow, practically irreversible inhibition of jack bean a-D-mannosidase by swainsonine is represented by the interaction of castanospermine with isomaltase and rat-intestinal sucrase. Whereas the association constants for the formation of the enzyme-inhibitor complex were similar to those of other slow-binding glycosidase inhibitors (6.5 10 and 0.3 10 M s for sucrase and isomaltase, respectively), the dissociation constant of the enzyme-inhibitor complex was extremely low (3.6 10 s for sucrase) or could not be measured at all (isomaltase), resulting in a virtually irreversible inhibition. Danzin and Ehrhard discussed the strong binding of castanospermine in terms of the similarity of the protonated inhibitor to a D-glucosyl oxocarbenium ion transition-state, but were unable to give an explanation for the extremely slow dissociation of the enzyme-inhibitor complex. 

Group (c), a-D-mannosidase from jack beans and from almonds, and a-D-galactosidase from coffee beans, showed no inactivation. The results with these enzymes can possibly be explained by the formation of a (weak) non-covalent complex in which glycosylation is too slow to cause inactivation within the time period of measurements, or, less likely, rapid hydrolysis of the glycosyl-enzyme intermediate. 

The protein-bound oligosaccharide is then partially processed by glucosidases and mannosidases if no additional sugars are added, this results in a high-mannose chain. 

For example, prior action of GIcNAc transferase I is necessary for the action of Golgi a-mannosidase II. 

HEMPAS (MIM 224100) Abnormalities in certain enzymes (eg, mannosidase II and others) involved in the biosynthesis of N-glycans, particularly affecting the red blood cell membrane. 

Colgate, S. M., Dorling, P. R. and Huxtable, C. R. 1979. A spectroscopic investigation of swainsonine an a-mannosidase inhibitor isolated from Swainsona canescens. Austral. J. Chem. 32 2257-2264. 

Base-catalyzed nitromethane cyclization of the dialdehyde generated by periodate oxidation of 1,2-O-cyclohexylidene-myo-inositol affords the nitrodiol with 1,4/2,3,5-configuration. This is converted into the a-mannosidase inhibitor, mannostatin A (Eq. 3.60).98... 

S. Singh, M. Scigelova, and D. H. G. Crout, Glycosidase-catalysed synthesis of mannobioses by the reverse hydrolysis activity of alpha-mannosidase Partial purification of alpha-mannosidases from almond meal, limpets and Aspergillus niger, Tetrahedron Asymmetry, 11 (2000) 223-229. 

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