Beta-hexosaminidase

Enzyme involved in the breakdown of glycosaminoglycans

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Structure of Beta-hexosaminidase

Identifiers
EC number	3.2.1.52
CAS number	9001-62-1
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Beta-hexosaminidase is an enzyme that plays a crucial role in the lysosomal degradation of glycosaminoglycans and glycolipids. It is a member of the glycoside hydrolase family and is responsible for the hydrolysis of terminal N-acetylhexosamines from glycoconjugates.

Structure

Beta-hexosaminidase is a dimeric enzyme composed of two subunits, commonly referred to as the alpha and beta subunits. The enzyme exists in multiple isoforms, including Hex A (alpha-beta), Hex B (beta-beta), and Hex S (alpha-alpha). Each isoform has distinct substrate specificities and physiological roles.

Function

The primary function of beta-hexosaminidase is to cleave N-acetylglucosamine and N-acetylgalactosamine residues from the non-reducing end of glycoconjugates. This enzymatic activity is essential for the normal turnover of glycolipids and glycoproteins in the lysosome.

Clinical Significance

Deficiency in beta-hexosaminidase activity is associated with several lysosomal storage disorders, most notably Tay-Sachs disease and Sandhoff disease. These conditions result from the accumulation of GM2 gangliosides in the nervous system, leading to progressive neurodegeneration.

Tay-Sachs Disease

Tay-Sachs disease is caused by a deficiency in the Hex A isoform, leading to the accumulation of GM2 gangliosides. It is an autosomal recessive disorder characterized by developmental delay, motor weakness, and a "cherry-red spot" on the retina.

Sandhoff Disease

Sandhoff disease is similar to Tay-Sachs but results from a deficiency in both Hex A and Hex B isoforms. It is also an autosomal recessive disorder and presents with similar neurological symptoms.

Biochemical Pathway

Beta-hexosaminidase is involved in the catabolic pathway of glycosphingolipids. It acts downstream of beta-galactosidase and upstream of sialidase in the degradation of GM2 gangliosides to GM3.

Research and Therapeutic Approaches

Research into beta-hexosaminidase has focused on understanding its structure-function relationship and developing enzyme replacement therapies for related disorders. Gene therapy and substrate reduction therapy are also being explored as potential treatments.

Also see

• Lysosomal storage disease
• Glycosaminoglycan
• Enzyme replacement therapy
• Glycoside hydrolase