Aldolase: An Important Enzyme in Metabolism and Disease Diagnosis
Aldolase is an enzyme that plays a crucial role in glucose metabolism, with three distinct isozymes (A, B, and C) distributed in different tissues, and serves as a valuable diagnostic marker for various muscle, liver, and other disorders. 1
Biochemical Role and Structure
Aldolase (EC 4.1.2.13) is a key enzyme in glycolysis and gluconeogenesis with the following characteristics:
- Molecular weight of approximately 160 kDa 1
- Catalyzes the reversible conversion of fructose-1,6-bisphosphate (FBP) to dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP) 2
- Exists as three distinct isozymes with tissue-specific distribution:
- Aldolase A: Predominant in skeletal muscle and erythrocytes
- Aldolase B: Predominant in liver
- Aldolase C: Predominant in brain 1
Clinical Significance
Muscle Disorders
Serum aldolase levels, particularly aldolase A isozyme, are elevated in:
In myositis evaluation, aldolase is considered one of the core enzyme measurements alongside other muscle enzymes like creatine kinase (CK) 3. The American College of Rheumatology includes aldolase in their criteria for evaluating response to treatment in dermatomyositis and polymyositis 3.
Liver Disorders
Aldolase B isozyme elevations are observed in:
- Acute hepatitis (markedly elevated)
- Chronic hepatitis (mildly elevated)
- Cirrhosis (mildly elevated)
- Obstructive jaundice (mildly elevated) 1
Other Clinical Applications
- Myocardial infarction: Rises within 24-48 hours and normalizes within 5 days 1
- Malignant tumors: Often shows elevation with predominance of isozyme A 1
- Hemolytic anemia: Elevated due to high concentration in erythrocytes 1
Diagnostic Utility
Aldolase is particularly useful in the diagnostic workup of:
Immune-related adverse events: In patients receiving immune checkpoint inhibitor therapy, aldolase is part of the recommended laboratory evaluation for suspected myositis 3
Inflammatory myopathies: Used alongside other muscle enzymes to assess disease activity and treatment response 3
Muscle injury vs. liver injury: When transaminases are elevated, aldolase testing can help differentiate between muscle injury and liver injury 3
Genetic Disorders Related to Aldolase
Aldolase A deficiency is an extremely rare autosomal recessive disorder characterized by:
- Hemolytic anemia
- Recurrent episodes of rhabdomyolysis (typically precipitated by fever)
- Mutations in the ALDOA gene 4
Biochemical Significance Beyond Metabolism
Aldolase has additional roles beyond its metabolic functions:
- Acts as a "chirality intersection" between L-amino acids and D-sugars in biological systems 5
- Interacts with various cellular proteins, including the Wiskott-Aldrich syndrome protein, potentially regulating actin dynamics 6
Emerging Research
Recent research has identified aldolase A as a potential therapeutic target in cancer, with efforts to develop inhibitors through high-throughput screening assays 2.
Important Considerations in Clinical Testing
- Aldolase levels should be interpreted in the context of other laboratory findings and clinical presentation
- Exercise can cause transient elevations in aldolase levels due to muscle activity 3
- When evaluating liver disease, aldolase may complement other liver function tests but is not typically a first-line test 7
Understanding aldolase's role in metabolism and its utility as a biomarker helps clinicians appropriately use this enzyme measurement in diagnosing and monitoring various disease states, particularly those affecting muscle and liver tissues.