Erythrocyte metabolism.

Erytrocytes play a key role in transporting oxygen from the lungs into tissues. Because of this, the structure and metabolism of erythrocytes are adapted to this function. Therefore, they cannot generate ATP by oxidative phosphorylation. The source of energy for the erythrocyte is D-glucose. They rely on a procces called glycolysis where glucose is broken down to produce energy.

Red blood cells, along with brain cells, are the only cells in the human body that require a continuous supply of glucose. The glucose transporter in the erythrocyte membrane - GLUT-1 contains 12 transmembrane helical segments that create a channel for the passage of glucose in the membrane. The transporter is not dependent on insulin.

Anaerobic glycolysis

Erythrocytes rely exclusively on anaerobic glycolysis for ATP production because they lack mitochondria. This pathway provides the necessary energy for maintaining ion gradients, membrane stability, and hemoglobin function.

Glucose enters the erythrocyte via GLUT1 by facilitated diffusion. Glucose → Pyruvate, producing 2 ATP and NADH. Pyruvate is converted to lactate to regenerate NAD⁺.

Although glycolysis in erythrocytes follows the same steps as in other cells, it differs at the phosphoglycerate kinase (PGK) step due to an alternative pathway known as the Rapoport–Luebering shunt.

2.Rapoport–Luebering Shunt If the erythrocyte does not require a high amount of ATP, instead of converting 1,3-bisphosphoglycerate (1,3-BPG) to 3-phosphoglycerate (3-PG) (which generates ATP), it diverts 1,3-BPG through the Rapoport–Luebering pathway. Bisphosphoglycerate mutase catalyzes the conversion of 1,3-BPG to 2,3-bisphosphoglycerate (2,3-BPG). 2,3-BPG binds to deoxyhemoglobin, stabilizing it in the T (tense) state. This reduces hemoglobin’s oxygen affinity, facilitating oxygen release to tissues. It is crucial for oxygen unloading, particularly in tissues with high metabolic activity or low oxygen availability. 3. Pentose Phosphate Pathway (PPP) in Erythrocytes

The PPP in erythrocytes is crucial for NADPH production and protection against oxidative damage, as RBCs lack mitochondria. This process has 2 pathways.

1. Oxidative Phase: G6PD produces NADPH and converts glucose-6-phosphate into ribulose-5-phosphate. NADPH and is essential for maintaining reduced glutathione (GSH), which protects RBCs from oxidative stress and damage to hemoglobin.

2. Non-Oxidative Phase: Ribose-5-Phosphate (R5P) is converted into glycolytic intermediates, like fructose-6-phosphate (F6P) and glyceraldehyde-3-phosphate (G3P) ensuring glucose isn't wasted.

https://www.sciencedirect.com/topics/immunology-and-microbiology/erythrocyte-metabolism https://pmc.ncbi.nlm.nih.gov/articles/PMC10386156/ https://ashpublications.org/blood/article/106/13/4034/133232/The-energy-less-red-blood-cell-is-lost-erythrocyte