Aldolase B

Aldolase B, also known as fructose-bisphosphate aldolase B, is an enzyme that in humans is encoded by the ALDOB gene. It is one of the three isozymes of the aldolase family, the others being aldolase A (found predominantly in muscle and brain) and aldolase C (found in brain). Aldolase B is expressed mainly in the liver, kidney, and intestine, playing a critical role in carbohydrate metabolism by catalyzing the reversible conversion of fructose 1,6-bisphosphate and fructose 1-phosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P).

Function

Aldolase B facilitates the glycolysis and gluconeogenesis pathways, allowing for the metabolism of glucose and fructose. It is particularly important in the metabolism of dietary fructose, converting fructose 1-phosphate into DHAP and glyceraldehyde, which can then enter the glycolytic pathway. This enzyme's activity is crucial for maintaining energy balance in the body, especially during fasting states.

Genetic and Clinical Significance

Mutations in the ALDOB gene are associated with hereditary fructose intolerance (HFI), a genetic disorder that results in an inability to properly digest fructose. Individuals with HFI may experience symptoms such as hypoglycemia, jaundice, and vomiting upon ingestion of fructose, sucrose, or sorbitol. Diagnosis of HFI is typically based on genetic testing, dietary history, and sometimes liver biopsy. Management of the condition involves strict avoidance of foods containing fructose, sucrose, and soritol.

Structure

Aldolase B is a tetramer composed of four identical subunits. Each subunit contains an active site where the substrate binds and the catalytic reaction occurs. The enzyme's structure is crucial for its function, as alterations can affect substrate binding and catalysis, leading to diseases such as HFI.

Evolution

The aldolase family of enzymes is highly conserved across different species, indicating their fundamental role in metabolism. Aldolase B, in particular, has evolved to efficiently metabolize fructose, reflecting dietary changes and the availability of fructose in the environment.

Research

Research on aldolase B has focused on understanding its structure-function relationship, the effects of mutations on enzyme activity, and the development of potential treatments for HFI. Studies have also explored the enzyme's role in various metabolic pathways and diseases, offering insights into its broader significance in health and disease.