ALDOA - Fructose-Bisphosphate Aldolase A| Elisa - Clia - Antibody - Protein

Background:

Aldolase A is a tetrameric enzyme that plays a crucial role in glycolysis. ALDOA catalyzes one of the key steps in glycolysis, the conversion of fructose 1,6-bisphosphate into two three-carbon sugars: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). ALDOA is one of three aldolase isozymes in humans, the others being ALDOB (liver) and ALDOC (brain). Mutations in the ALDOA gene can lead to rare disorders such as Glycogen storage disease type XII, which affects glycogen metabolism.ALDOA has been implicated in various cancers, including lung cancer, breast cancer, and colorectal cancer. It's often found to be upregulated in cancer cells, where it promotes glycolysis, providing cancer cells with energy and building blocks for rapid growth. Due to its role in cancer metabolism, ALDOA is being investigated as a potential therapeutic target for cancer treatment. Inhibiting ALDOA could potentially starve cancer cells of their energy source.

Protein Structure:

• General Structure: ALDOA is a homotetramer, meaning it is composed of four identical subunits, each approximately 360 amino acids in length.
• Active Site: The active site of ALDOA includes key residues that interact with the substrate fructose 1,6-bisphosphate, catalyzing its cleavage into two three-carbon products: glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Key catalytic residues typically include lysine and glutamate.
• Isozyme Differences: While ALDOA shares structural similarities with ALDOB and ALDOC, it has specific amino acid sequences that confer unique kinetic properties and tissue-specific functions.

Classification and Subtypes:

• Isoforms: ALDOA is one of the three human aldolase isozymes. The classification is based on tissue distribution and function:
• ALDOA: Found in muscle and red blood cells.
• ALDOB: Found in the liver.
• ALDOC: Found in the brain.

Function and Biological Significance:

• Glycolysis: ALDOA catalyzes the fourth step in glycolysis, a key metabolic pathway for ATP production. It splits fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
• Energy Production: Essential for muscle cells during strenuous activity when rapid ATP generation is required.
• Red Blood Cell Function: Helps maintain energy balance and cell integrity in erythrocytes, which lack mitochondria and rely solely on glycolysis for energy.

Interactions:

• Metabolic Enzymes: ALDOA interacts with other glycolytic enzymes, ensuring efficient substrate channeling and metabolic flux.
• Structural Proteins: It binds to the cytoskeleton, particularly actin filaments, stabilizing cell structure and possibly regulating enzyme activity.

Clinical Issues:

• Myopathies: Mutations in the ALDOA gene can lead to muscle weakness and myopathy due to impaired glycolysis and energy production in muscle cells.
• Cancer: ALDOA is often upregulated in cancer cells to support increased glycolytic activity (the Warburg effect), which provides energy and metabolic intermediates for rapid cell proliferation.
• Hemolytic Anemia: Deficiencies in ALDOA can cause nonspherocytic hemolytic anemia, a condition where red blood cells are destroyed prematurely due to insufficient energy production.

Summary:

ALDOA is a critical glycolytic enzyme, predominantly found in muscle tissue and red blood cells, where it plays a vital role in energy production. It catalyzes a key step in glycolysis, converting fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. ALDOA's proper function is essential for muscle activity and red blood cell integrity. Mutations or altered expression of ALDOA can lead to various clinical issues, including myopathies, hemolytic anemia, and cancer metabolism, highlighting its importance in both health and disease.