D-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. 

G. Legler and E. Jiilich, Synthesis of 5-amino-5-deoxy-D-mannopyranose and l,5-dideoxy-l,5-imino-D-mannitol, and inhibition of a- and P-D-mannosidases, Carbohydr. Res., 128 (1984) 61-72. 

A. E. Hakansson, J. van Ameijde, L. Guglielmini, G. Home, R. J. Nash, E. L. Evinson, A. Kato, and G. W. J. Fleet, Looking glass inhibitors Synthesis of a potent naringinase inhibitor l-DIM (l,4-dideoxy-l,4-imino-L-mannitol), the enantiomer of DIM (l,4-dideoxy-l,4-imino-D-mannitol) a potent a-D-mannosidase inhibitor, Tetrahedron Asymmetry, 18 (2007) 282-289. 

One particular example of the early extraction of a chemical from a plant, a small tree found in the rainforests of eastern Queensland, would be that of acronycine 1 [1,2], an alkaloid currently undergoing clinical trials as an anticancer agent. More recently, a group in Perth at Murdoch University succeeded in extracting the alkaloid, swainsonine 2 from a desert shrub which causes poisoning in cattle [3]. Swainsonine has been found to exhibit an interesting spectrum of biological activity [4], especially as a potent, reversible inhibitor of various a-D-mannosidases [5]. 

There are two attributes of a-D-mannosidase (EC 3.2.1.24) that receive particular attention in this article, namely, its behavior as a zinc-containing metalloenzyme, and its action on naturally occurring, D-mannose-containing molecules. However, such more-systematic considerations as the kinetics of action and the distribution of the enzyme in Nature are not overlooked. 

Early work on a-D-mannosidase of plant origin, notably in almond emulsin, has been described.1 There has been a revival of interest in the enzyme from all sources, and an extensive survey of plant... 

Since Lewy and coworkers5 first showed that a-D-mannosidase occurs in mammals, its presence has been detected in virtually every... 

Ovariectomy caused a pronounced fall in the a-D-mannosidase activity of mouse uterus, and the normal level was restored by administration of estrone.28 Although the ovary is not particularly rich in a-D-man-nosidase, the greater proportion of the activity in cattle, pig, and human ovaries was found to be concentrated in the corpus luteum.14,28... 

Results are expressed as fig of p-nitrophenol liberated per g of seed from 6 mM p-nitrophenyl a-D-mannoside in 1 hr at 37° and pH 5. Coarsely ground beans. Defatted sweet-almond meal. A commercial /3-D-glucosidase preparation purified from emulsin. a-D-Mannosidase activity is given per g of purified material. 

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