D-Mannosidases

A pool of acid hydrolases exists within the acellular lining material of the alveoli and distal airways of the lungs.These extracellular hydrolases, obtained using pulmonary lavage procedures, appear to be of a selected variety insofar as some hydrolases (i8-D-2-acetamido-2-deoxyglucosidase and a-D-mannosidase) are highly active while others (j3-D-glucuronidase and arylsulphatase) are barely detectable (see p. 421). 

An abnormal, decreased thermostability of a-D-mannosidase has been found in crude extracellular fluids of patients with cystic fibrosis and carriers thereof.  

Decreased binding by the lectins concanavalin A and wheat-germ agglutinin was found for a number of acid hydrolases ( -D-2-acetamido-2-deoxyhexo-sidase, a-L-fucosidase, a- and j3-D-glucosidases, jS-D-galactosidase, and a-D-mannosidase) from skin fibroblasts of three unrelated patients with mucolipidosis II (see p. 423).  

A search for lysosomal hydrolases and related enzymes has been made in haemolysates from human and rabbit red cells. Apart from acid phosphatases, significant activities were found only for a-D-mannosidase, neutral o-D-glucosidase, and -D-2-acetamido-2-deoxyhexosidase. a-D-Mannosidase activity per cell in human red blood cells was 200-times lower than in white cells. The optimal pH was 5.5-6.0. Electrophoresis on cellulose acetate showed three bands. Haemolysates from four patients with mannosidosis were not deficient in a-D-mannosidase. Curves of pH activity and electrophoretic patterns were similar to those of controls. From its biochemical and genetic properties, it is concluded that red cell a-D-mannosidase differs from the lysosomal acid a-D-mannosidase. 

Residual acid a-D-mannosidase, varying in amount up to approximately 15 % of normal values, can be measured in various organs of a calf with manno- 

The mechanism of action of a-D-mannosidase has been discussed. Oligosaccharides containing terminal, non-reducing a-(l - 2)-, oc-(l 3)-, and a-(l 6)-linked o-mannosyl residues, which were isolated from the urines of humans and cattle with mannosidosis, have been used to ascertain the substrate specificities of acid a-D-mannosidases obtained from human and bovine livers. Differences in the activities of A and forms of the enzyme were shown with all substrates. The C form (pH optimum ca. 7) did not hydrolyse any of the oligosaccharides at neutral pH, but it was active at a lower pH. 

The isolation and properties of human-kidney a-D-mannosidase have been reported. The levels of a-D-mannosidase activity in human body fluids, including sera and urine, have been monitored during ageing.  

The jS-D-mannosidase activity in cultures of human-skin fibroblasts and the a-D-mannosidase activities of human epidermoid carcinoma KB cells have 

Hultberg, A. Lundblad, P. K. Masson, and P. A. Ockerman, Biochim. Biophys. Acta, 

The effects of 2-acetamido-2,3-dideoxy-D-eryt/jro-hex-2-enono-l,4-lactone on the activities of (x-D-mannosidases from bovine epididymis and almond emulsin have been investigated.  

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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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