mannosidases

Mannosidases are enzymes that hydrolyze mannose-containing glycosidic bonds in glycoproteins, oligosaccharides, and polysaccharides. They are exo-acting hydrolases that remove terminal alpha- or beta-mannose residues from complex carbohydrates in a stepwise fashion.

Mannosidases are grouped by the configuration of the cleaved linkage into alpha- (alpha-mannosidases) and beta- (beta-mannosidases) classes. In eukaryotes, several enzymes trim N-linked glycans along the secretory pathway in the endoplasmic reticulum and Golgi, helping to produce mature complex-type structures. In lysosomes, acid hydrolases such as lysosomal alpha-mannosidase degrade stored glycoproteins and oligosaccharides.

Biological roles and distribution: Mannosidases are found in bacteria, fungi, plants, and animals. They participate in the catabolism of mannose-containing polysaccharides and in processing of N-glycans on secreted glycoproteins. In humans, mutations in MAN2B1 cause alpha-mannosidosis, a lysosomal storage disorder with skeletal, neurological, and immune symptoms. Beta-mannosidase deficiency (beta-mannosidosis) is rarer and presents with variable features.

Clinical and research aspects: Diagnosis relies on reduced enzymatic activity and genetic testing. Treatments are supportive; enzyme replacement and gene therapies are areas of investigation for some forms of mannosidosis. Mannosidases are also used as analytical tools in glycoprotein analysis and glycobiology, helping to trim glycans for structural studies and biotherapeutic optimization.