2,3-Bisphosphoglycerate pathway in erythrocytes || Rapoport luebering cycle || #Biochemistry

Summary

This video explains the 2,3-bisphosphoglycerate (2,3-BPG) pathway in red blood cells, detailing its formation and significance in oxygen delivery. The Rapoport-Luebering pathway, which involves the conversion of glucose through glycolysis to produce 2,3-BPG, plays a key role in regulating oxygen offloading from hemoglobin. The video also covers the effects of 2,3-BPG in various conditions like chronic hypoxia, high altitudes, and fetal hemoglobin. Additionally, it discusses the challenges with stored blood and how rejuvenation solutions can restore 2,3-BPG levels. The content is informative for those interested in biochemistry and physiology.

Takeaways

• 😀 2,3-Bisphosphoglycerate (2,3-BPG) pathway, also called the Rapoport-Luebering pathway, is crucial for regulating oxygen delivery in red blood cells (RBCs).
• 😀 The pathway starts with glucose in the glycolytic process but diverges at 1,3-BPG, where it forms 2,3-BPG via bisphosphoglycerate mutase.
• 😀 Unlike the regular glycolytic pathway, the Rapoport-Luebering cycle does not generate ATP, but helps maintain proper levels of 2,3-BPG in RBCs.
• 😀 2,3-BPG binds to hemoglobin, stabilizing the T (deoxygenated) form and lowering its affinity for oxygen, thus facilitating oxygen offloading to tissues.
• 😀 The binding of 2,3-BPG shifts the oxygen dissociation curve to the right, enhancing oxygen release from hemoglobin to the tissues in need.
• 😀 2,3-BPG acts as a buffer in RBCs, adapting to changes in oxygen and CO2 concentrations in the body.
• 😀 In conditions like chronic hypoxia, smoking-related diseases, high altitudes, and chronic anemia, 2,3-BPG levels increase to improve oxygen delivery to tissues.
• 😀 2,3-BPG also rises in physiological states such as exercise, pregnancy, and alkalosis, where oxygen demand or environmental conditions change.
• 😀 In fetal hemoglobin (HbF), the gamma chains bind 2,3-BPG less effectively than adult hemoglobin's beta chains, giving HbF a higher oxygen affinity, which is crucial for oxygen transfer from mother to fetus.
• 😀 Stored blood undergoes reduced 2,3-BPG levels due to depleted glucose, which increases the oxygen affinity of hemoglobin, making it less effective for oxygen delivery. Rejuvenation solutions can restore 2,3-BPG levels in stored blood.

Q & A

What is the 2,3-Bisphosphoglycerate (2,3-BPG) pathway also known as?

The 2,3-Bisphosphoglycerate pathway is also known as the Rapoport-Luebering pathway, named after Rapoport and his assistant Luebering, who first described and isolated it in 1925.

Where does the 2,3-BPG pathway primarily occur?

The 2,3-BPG pathway primarily occurs in erythrocytes (red blood cells, or RBCs).

How is 2,3-BPG formed in the glycolytic pathway?

2,3-BPG is formed when 1,3-bisphosphoglycerate, an intermediate in glycolysis, is isomerized into 2,3-BPG by the enzyme bisphosphoglycerate mutase (BPGM).

What is the key difference between the glycolytic pathway and the Rapoport-Luebering pathway?

The key difference is that while the glycolytic pathway generates ATP, the Rapoport-Luebering pathway does not produce ATP but instead regulates the level of 2,3-BPG, which modulates oxygen release from hemoglobin.

How does 2,3-BPG affect hemoglobin's ability to bind oxygen?

2,3-BPG binds to deoxygenated hemoglobin, stabilizing its T (tense) state and reducing its affinity for oxygen. This facilitates oxygen offloading to tissues that need it.

Which amino acids are involved in the binding of 2,3-BPG to hemoglobin?

The amino acids involved in binding 2,3-BPG to hemoglobin are lysine at position 82, histidine at position 140, and another lysine residue, all located on the beta-globin chains of hemoglobin.

How does 2,3-BPG influence the oxygen dissociation curve?

2,3-BPG causes a rightward shift in the oxygen dissociation curve, indicating a decreased affinity of hemoglobin for oxygen, which enhances the release of oxygen to tissues.

What factors increase the concentration of 2,3-BPG in red blood cells?

Factors such as chronic hypoxia (e.g., COPD, emphysema), high altitudes, chronic anemia, pregnancy, exercise, and alkalosis can increase the concentration of 2,3-BPG in RBCs.

Why does fetal hemoglobin have a higher affinity for oxygen than adult hemoglobin?

Fetal hemoglobin binds 2,3-BPG less strongly than adult hemoglobin because the gamma chains in fetal hemoglobin contain serine at position 140, instead of histidine in adult hemoglobin, leading to a higher affinity for oxygen.

What is the issue with stored blood regarding 2,3-BPG, and how is it addressed?

Stored blood experiences a decrease in 2,3-BPG levels as glucose is metabolized, which increases the oxygen affinity of hemoglobin, making it less effective in releasing oxygen. This can be corrected by adding rejuvenation solutions containing phosphate, pyruvate, adenine, and glucose to restore 2,3-BPG levels in stored blood.