Function of Aldolase
Aldolase is a key enzyme in glycolysis that catalyzes the reversible conversion of fructose-1,6-bisphosphate to dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP), playing a crucial role in cellular energy metabolism. 1, 2
Types and Distribution of Aldolase
Three isozymes exist:
- Aldolase A: Predominant in skeletal muscle and erythrocytes
- Aldolase B: Primarily found in the liver
- Aldolase C: Mainly present in the brain
Aldolase is widely distributed throughout the body, with particularly high concentrations in muscles, liver, and brain 2
Biochemical Function
Aldolase functions as a tetrameric enzyme with a molecular weight of approximately 160 kDa 2. Its primary metabolic role includes:
- Catalyzing a critical step in the glycolytic pathway
- Participating in gluconeogenesis (the reverse reaction)
- Contributing to energy production through ATP generation
The enzyme contains a hydrophobic pocket in its active site that mediates interactions with various cellular proteins, including the Wiskott-Aldrich syndrome protein 3. This structural feature allows aldolase to perform both its catalytic function and engage in protein-protein interactions.
Clinical Significance
Diagnostic Applications
Aldolase serves as an important biomarker in several clinical contexts:
- Muscle disorders: The American College of Rheumatology includes aldolase in their criteria for evaluating response to treatment in dermatomyositis and polymyositis 4, 1
- Liver diseases: Aldolase B isozyme elevations occur in acute hepatitis, while milder elevations are seen in cirrhosis, chronic hepatitis, and obstructive jaundice 2
- Cardiac conditions: Rises in myocardial infarction, reaching maximum levels within 24-48 hours 2
- Malignancies: Elevated in various solid tumors, with aldolase A being the predominant isozyme 2, 5
Pathological Conditions
- Aldolase A deficiency: An extremely rare autosomal recessive disorder characterized by:
- Hemolytic anemia
- Recurrent episodes of rhabdomyolysis, usually precipitated by fever 6
Research Applications
Recent research has explored aldolase inhibition as a potential therapeutic target:
- High-throughput screening has identified compounds like merbromin and ellagic acid as noncompetitive inhibitors of aldolase A 7
- Aldolase A has been identified as a potential metastasis-associated marker in lung squamous cell carcinoma, suggesting its role in cancer progression 5
Monitoring Disease Activity
When monitoring disease activity, particularly in inflammatory myopathies:
- Improvement in aldolase levels correlates with treatment response
- The American College of Rheumatology considers a >40% improvement in enzyme levels (including aldolase) as a significant marker of treatment response 4
Understanding aldolase's function and clinical applications provides valuable insights for diagnosing and monitoring various pathological conditions, particularly those affecting muscle, liver, and metabolic pathways.