HEXA - Beta-Hexosaminidase Subunit Alpha | Elisa - Clia - Antibody - Protein

Background:

Hexosaminidase A (alpha polypeptide), also known as HEXA, corresponds to an enzyme encoded by the HEXA gene in humans. However, it's important to note that there is a chromosomal difference between humans and mice, with the HEXA gene located on chromosome 9 in humans and chromosome 15 in mice.The primary function of Hexosaminidase A, along with the cofactor GM2 activator protein, is to facilitate the degradation of GM2 gangliosides and other molecules containing terminal N-acetyl hexosamines.The HEXA gene in humans spans approximately 26 kb and is composed of 14 exons and 13 introns. In conjunction with the HEXB gene, which encodes the beta-subunit, these genes collectively produce human beta-hexosaminidase, with HEXA responsible for the alpha-subunit. In mice, the equivalent genes are termed Hexa and Hexb.The subunits of beta-hexosaminidase, when they come together, form three distinct isozymes: beta-hexosaminidase A (alpha beta), beta-hexosaminidase B (beta beta), and beta-hexosaminidase S (alpha alpha). These isozymes possess the capability to break down various substrates that contain beta-linked N-acetylglucosamine and N-acetylgalactosamine residues.

Protein Structure:

Beta-hexosaminidase A is a heterodimer composed of an alpha subunit (encoded by HEXA) and a beta subunit (encoded by HEXB). The mature alpha subunit has 529 amino acids and includes several glycosylation sites that are important for its stability and function. The enzyme's structure allows it to bind and hydrolyze GM2 gangliosides efficiently within the lysosome.

Classification and Subtypes:

Beta-hexosaminidase A is one of three isoenzymes:

1. Hexosaminidase A (Hex A): Composed of one alpha and one beta subunit.
2. Hexosaminidase B (Hex B): Composed of two beta subunits.
3. Hexosaminidase S (Hex S): Composed of two alpha subunits, which is very rare and not commonly found in humans.

Function and Biological Significance:

• Lysosomal Function: Hex A is responsible for breaking down GM2 gangliosides into simpler molecules that can be recycled or further degraded. This process is critical for normal cellular function and neuronal health.
• GM2 Ganglioside Degradation: GM2 gangliosides are complex lipids found in neuronal cell membranes. The accumulation of GM2 gangliosides due to deficient Hex A activity leads to cell dysfunction and death, particularly affecting neurons.

Interactions:

• GM2 Activator Protein: This protein facilitates the interaction between Hex A and its substrate, GM2 ganglioside, enhancing the enzyme's efficiency in catalyzing the hydrolysis.
• Beta Subunit (HEXB): The beta subunit, encoded by HEXB, forms a heterodimer with the alpha subunit to create the active Hex A enzyme. Both subunits are necessary for proper enzymatic activity.

Clinical Issues:

• Tay-Sachs Disease: This autosomal recessive disorder results from mutations in the HEXA gene leading to a deficiency in Hex A activity. Symptoms include developmental delay, loss of motor skills, seizures, vision and hearing loss, and premature death. There is currently no cure, and treatment focuses on managing symptoms and supportive care.
• Carrier Screening: Genetic screening for HEXA mutations is important in populations with a higher incidence of Tay-Sachs disease, such as Ashkenazi Jews, to identify carriers and reduce the incidence of the disease through informed family planning.

Summary:

The HEXA gene encodes the alpha subunit of beta-hexosaminidase A, an enzyme critical for the degradation of GM2 gangliosides in lysosomes. Mutations in HEXA lead to Tay-Sachs disease, a severe neurodegenerative disorder characterized by the accumulation of GM2 gangliosides in neurons. Understanding the structure, function, and interactions of Hex A is crucial for diagnosing, managing, and potentially developing treatments for Tay-Sachs disease. Carrier screening programs have significantly impacted the incidence of this disease in high-risk populations.