2,3 Diphosphoglycerate (2,3 DPG, or 2,3 bisphosphoglycerate, or 2,3 BPG)
3 factors that affect oxygen binding:
• Hydrogen ions
• Covalent binding of CO2
• 2,3 DPG binding
Formation of 2,3 DPG
• formed in red blood cells from the glycolytic intermediate 1,3 bisphosphoglycerate through the Rapoport-Luberin shunt
• red blood cells contain 4-5 mM 2,3 DPG; trace amounts in other cells
• 2,3 DPG is a modulator of oxygen binding to hemoglobin that stabilizes the deoxy form of hemoglobin, facilitating oxygen release to tissues
General information about Hemoglobin (Hb)
• major transporter of oxygen from lungs to tissue
• there are a few different forms of Hb, w/ HbA being the major adult form
• Hb is tetrameric and has 2 alpha and 2 beta chains
• Hb operates as two αβ dimers. The α and β chains are bound tightly through electrostatic interactions***
• 1 Hb binds 4 molecules of oxygen, one/heme group
• Oxygen binding is cooperative in that once one oxygen unit binds, it facilitates binding to other subunits—why the oxygen dissociation curve is sigmoidal
• Two forms of Hb, relaxed, “R”, or taut, “T”. The relaxed form is the oxygenated state, and the taut form is the deoxygenated state
Binding
• 2,3 DPG binds to the beta-chain of Hb in the central cavity formed by the 4 subunits, which increases the energy required for conformational changes that normally facilitate binding of oxygen
• when Hb contains 2,3 DPG, there is less affinity for oxygen binding
• less oxygen is bound and therefore is more available to tissues
• has the Bohr effect, shifts the oxygen dissociation curve to the right
• oxygen does not bind as easily to Hb and is released more easily from Hb
Conditions that increase levels of 2,3 DPG (and better delivery of O2 to tissues)
• emphysema
• high altitudes (decreased partial pressure of O2)
• chronic anemia
Resources:
Mark’s Medical Biochemistry A Clinical Approach by Smith, Marks, and Lieberman p808-815
Harper's Illustrated Biochemistry 27th Edition by Murray, Granner, Rodwell (online book) Chapter 6
Carolyn
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