3-D-Glucosidases

The common identity of human acid ]0-D-glucosidase and j3-D-xylosidase is indicated by similar binding patterns of the glycoside hydrolase activities of each enzyme to various lectins, by similar ratios between their intra- and extracellular levels in normal and I-cell fibroblasts, and by their deficiencies in liver tissues from patients with Gaucher disease,  

D-Gluconamide, D-gluconyl hydrazide, and iV-(6-aminohexyl)-D-gluconamide have been tested for their inhibitory action on human liver lysosomal gluco-cerebrosidase and human spleen neutral aryl jS-D-glucosidase (see p. 437). 

Decreased binding by the lectins concanavalin A and wheat-germ agglutinin was found for a number of acidic hydrolases (/3-D-2-acetamido-2-deoxyhexo-sidase, a-L-fucosidase, a- and /3-D-glucosidases, j3-D-galactosidase and a-D-manno-sidase) from skin fibroblasts of three unrelated patients with mucolipidosis (see p. 423).i 

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 a-D-glucosidase and 3-D-2-acetamido-2-deoxyhexosidase. 

The isoenzymes of a-D-glucosidases have been studied in human white blood cells by immunological and electrophoretic techniques.Three isoenzymes have been found in leucocyte extracts lysosomal a-D-glucosidase ( acid maltase, glucoamylase), cytoplasmic neutral oi-D-glucosidase, and an enzyme immuno-logically identical to renal maltase (a-D-glucosidase). In Pompe s disease and other types of acid maltase deficiency, the deficiency is as complete in leucocytes as in other tissues, and the residual activity is due to renal maltase . 

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In order to develop potent D-glucosidase inhibitors, a synthesis of carba-disaccharides containing valiolamine (205) was attempted by Horii and his coworkers utilizing method c. Coupling 205 with the 4-ketose 403, using NaBHjCN and hydrochloric acid, was effective in DMF, giving, after deprotection, the epimeric carba-disaccharides (404 and 405). The saturated... 

The question of a correlation of anomeric specificity of glycosidases with their susceptibility to aldonolactone inhibition was addressed by Reese and coworkers in a comparative study with six fungal a-D-glucosidases and... 

A straightforward discrimination between the two pathways is possible with enzymes that are inhibited by basic glycosyl derivatives as well as by permanently cationic ones. This is illustrated by )S-D-glucosidase A3 from Asp. wentii, where K4 values for yS-D-glucosylpyridinium ion, / -D-glucosyla-... 

The importance of a basic nitrogen atom for strong inhibition by the indolizine type of inhibitor is demonstrated by the finding that I for inhibition by castanospermine A -oxide of the ) -D-glucosidase from almonds is 500-fold larger than of castanospermine itself (760 fiM V5. 1.5 /lA/at pH... 

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

When the accessible concentration range of glycal [A] c Kj and kpg- c khydr as for ) -D-galactosidase from E. coli, this reduces to k (1 + [S]/ Kp,) = (kp /K,0 [A] + khydf. The rate constant k yj, for the addition of water has to be measured separately, by the appearance of the 2-deoxy-o-hexose. With )S-D-galactosidase from E. and yS-D-glucosidase from... 

The type of intermediate that is formed in the slow inhibition with D-gly-cals was identified, with the aid of the ) -D-glucosidase A3 from Asp. wentii, as an ester of 2-deoxy-D-araA/ o-hexose with an aspartic acid side-chain. The same aspartoyl residue had already been shown, by labeling with con-duritol B epoxide (see Section 111,1), to be essential for -D-glucoside hydrolysis. In addition, this aspartate was found to form a glycosyl -enzyme... 

Scheme 3.—Formation of 2-Deoxy-a-D-arahino-hexosyl Enzyme from D-Glucal at the Active Site of a )3-D-Glucosidase.

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