ALDOB - Fructose-Bisphosphate Aldolase B | Elisa - Clia - Antibody - Protein

Background:

ALDOB, is involved in the glycolysis pathway, specifically catalyzing the reversible cleavage of fructose 1-phosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde. ALDOB is primarily expressed in the liver, kidney, and small intestine. Mutations in the ALDOB gene can lead to HFI, (Hereditary Fructose Intolerance) a rare genetic disorder where affected individuals lack the enzyme ALDOB, resulting in an inability to properly metabolize fructose. This can lead to symptoms like nausea, vomiting, abdominal pain, and even liver damage when fructose is consumed. ALDOB is found predominantly in the liver cells (hepatocytes) and to a lesser extent in the cells of the kidney and small intestine. ALDOB specifically helps break down fructose in the liver, converting it into usable energy sources for the body. ALDOB deficiency can be detected through genetic testing and measurement of ALDOB enzyme activity. In individuals suspected of having HFI, a liver biopsy can show reduced ALDOB activity. ALDOB and ALDOA, while both involved in glycolysis, have different tissue distributions and specificities. ALDOB is more liver-specific, while ALDOA is found in a broader range of tissues.

Protein Structure:

• General Structure: ALDOB, like its isozyme counterparts, is a homotetramer composed of four identical subunits. Each subunit is approximately 364 amino acids in length.
• Active Site: The active site of ALDOB contains key residues essential for binding and cleaving fructose 1,6-bisphosphate and fructose 1-phosphate into their respective products.
• Isozyme Differences: The primary structure of ALDOB differs from ALDOA and ALDOC, giving it unique kinetic properties and substrate affinities suitable for its role in fructose metabolism.

Classification and Subtypes:

Isoforms: ALDOB is one of the three human aldolase isozymes, with each isozyme localized in different tissues:

• ALDOA: Found in muscle and red blood cells.
• ALDOB: Found in the liver, kidney, and intestine.
• ALDOC: Found in the brain.

Function and Biological Significance:

• Glycolysis: ALDOB catalyzes a crucial step in glycolysis by cleaving fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
• Fructose Metabolism: It also plays a pivotal role in fructose metabolism by cleaving fructose 1-phosphate into dihydroxyacetone phosphate and glyceraldehyde. This is particularly important after the ingestion of fructose-containing foods.
• Gluconeogenesis: ALDOB is involved in gluconeogenesis, the metabolic pathway that generates glucose from non-carbohydrate substrates, particularly during fasting.

Interactions:

• Metabolic Pathways: ALDOB interacts with various enzymes in glycolysis and gluconeogenesis, facilitating efficient substrate conversion and energy production.
• Regulatory Proteins: It may interact with other proteins that regulate its activity and stability in response to metabolic needs.

Clinical Issues:

• Hereditary Fructose Intolerance (HFI): Mutations in the ALDOB gene cause hereditary fructose intolerance, a condition where individuals lack the ability to properly metabolize fructose. This leads to the accumulation of toxic metabolites, causing symptoms like hypoglycemia, abdominal pain, and vomiting upon fructose ingestion.
• Liver Diseases: Abnormal ALDOB expression or function can contribute to liver pathologies, as the liver is a major site of fructose metabolism.
• Cancer: Similar to ALDOA, ALDOB expression can be altered in certain cancers, potentially affecting tumor metabolism and growth.

Summary:

ALDOB is a critical enzyme in the liver, kidney, and intestine, facilitating both glycolysis and fructose metabolism. It cleaves fructose 1,6-bisphosphate and fructose 1-phosphate, playing essential roles in energy production and glucose synthesis. Mutations in the ALDOB gene lead to hereditary fructose intolerance, highlighting the enzyme's importance in proper metabolic functioning. ALDOB's role extends to potential implications in liver diseases and cancer metabolism, underscoring its biological significance.