Metabolism in Erythrocytes (RBCs)
- Mature RBCs lack mitochondria and nuclei. This means they cannot perform the Citric Acid Cycle, β-oxidation, or oxidative phosphorylation.
- Therefore, RBCs depend entirely on anaerobic glycolysis for ATP production.
They convert glucose to lactate, producing 2 ATP per glucose.
- Glucose enters RBCs through GLUT1, which is insulin-independent, so RBC glucose uptake does not vary with insulin levels.
Main Metabolic Pathways in RBCs
1) Anaerobic Glycolysis (Embden–Meyerhof Pathway)
- Major source of ATP in RBCs.
- ATP is required for: – Maintaining Na⁺/K⁺-ATPase to preserve cell shape and osmotic balance. – Maintaining membrane flexibility (so RBCs can pass through capillaries).
- End product is lactate, which diffuses to the blood and is transported to liver for the Cori cycle.
2) Pentose Phosphate Pathway (PPP / HMP Shunt)
- RBCs use this pathway to generate NADPH, not ATP.
- NADPH maintains glutathione in reduced form (GSH).
- GSH protects RBCs from oxidative damage (e.g., hydrogen peroxide, free radicals).
Without GSH, hemoglobin becomes oxidized → forms Heinz bodies → membrane damage → hemolysis.
- G6PD is the key enzyme here.
Deficiency → hemolytic anemia, especially after oxidative stress (fava beans, infections, antimalarial drugs).
3) Rapoport–Luebering Shunt (2,3-BPG Pathway)
- RBCs divert 1,3-BPG from glycolysis to synthesize 2,3-bisphosphoglycerate (2,3-BPG).
- 2,3-BPG binds to deoxygenated hemoglobin, reducing its affinity for oxygen.
This promotes oxygen release to tissues, especially in: – High altitude – Hypoxia – Chronic anemia
- If 2,3-BPG decreases → RBCs hold onto oxygen → tissues become hypoxic.