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04
Feb
Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)
A Dual-Function Enzyme: From Glycolytic Pillar to Regulatory Mastermind
Key Highlights
- Central Metabolism: Catalyzes the 6th step of glycolysis.
- Moonlighting Functions: Involved in DNA repair, apoptosis, and gene expression.
- Clinical Biomarker: Early indicator for MI and various metabolic disorders.
Biological Function & Regulation
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a cornerstone enzyme of the glycolytic pathway. It facilitates the oxidation and phosphorylation of glyceraldehyde-3-phosphate (G3P).
The Glycolytic Reaction:
$Glyceraldehyde\text{-}3\text{-}phosphate + NAD^+ + P_i \rightleftharpoons 1,3\text{-}bisphosphoglycerate + NADH + H^+$
Beyond its metabolic home, GAPDH is a "moonlighting" protein. Its function shifts based on Post-Translational Modifications (PTMs) like S-nitrosylation or phosphorylation, leading to its translocation from the cytosol to the nucleus during cellular stress.
Clinical Significance & Pathophysiology
| Condition | Mechanism / Role of GAPDH |
|---|---|
| Myocardial Infarction | Early serum biomarker; elevates sooner than CK or AST. |
| COVID-19 | Inhibition triggers NETosis and inflammatory cytokine storms. |
| Sarcopenia | S-nitrosylation leads to p53-mediated myofiber apoptosis. |
| Oncology | Overexpressed in HCC, Lung Cancer, and Glioma; promotes survival. |
Broad Spectrum Impact
Neurodegeneration
Key mediator in Alzheimer's and Parkinson's through protein aggregation and neuronal apoptosis.
Liver & Kidney
Reflects hepatocellular damage in hepatitis and metabolic stress in chronic pyelonephritis.
Infectious Disease
Essential for energy in parasites (e.g., Plasmodium), making it a novel drug target.
Biofargo team
