2,3-Diphosphoglyceric acid

Table of Contents

• What is 2,3-DPG? – 2,3-DPG Meaning
• Formation
• Binding with Haemoglobin – 2,3-BPG Function
• Clinical Significance
• Frequently Asked Questions

What is 2,3-DPG? – 2,3-DPG Meaning

2,3-diphosphoglyceric acid (2,3-DPG) is an isomer of 1,3-bisphosphoglyceric acid (1,3-BPG), an intermediate of the glycolytic pathway. It is alternatively known as 2,3-Bisphosphoglyceric acid (2,3-BPG).

ᴅ-2,3-BPG is found in the red blood cells of humans and binds more readily to deoxygenated haemoglobin than to oxygenated haemoglobin because of its confirmation. It is an allosteric effector that increases the release of oxygen by interacting with deoxygenated haemoglobin and decreasing its affinity towards oxygen. This function of 2,3-DPG was first demonstrated by American scientists Ruth Benesch and Reinhold Benesch in 1967.

Formation

2,3-BPG is formed by isomerisation of 1,3-BPG, which is catalysed with the help of the enzyme BPG mutase. 2,3-BPG phosphatase then breaks it down to form 3-PGA (3-phosphoglycerate). The breakdown and synthesis of 2,3-BPG is involved in the step of glycolysis itself. The molecule is formed at the expense of an ATP molecule since a phosphate–carboxylate mixed-anhydride bond (a high energy bond) is broken by the mutase enzyme.

The glycolysis pathway creates 1,3-BPG and it is dephosphorylated by phosphoglycerate kinase (PK) at the expense of an ATP. It is then shunted into the Luebering-Rapoport pathway, here bisphosphoglycerate mutase catalyses the transfer of phosphate group from C1 to C2 and thus yielding 2,3-BPG.

A balance is required between the generation of ATP for energy production and the oxygenation/deoxygenation of haemoglobin molecules. This is achieved by isomerisation of 1,3-BPG to 2,3-BPG.

Binding with Haemoglobin – 2,3-BPG Function

Upon binding with 2,3-BPG, the deoxyhaemoglobin which is at low oxygen affinity state (T state) gets stabilised. It exploits the positive polarity and molecular symmetry of the deoxyhemoglobin and forms salt bridges with the lysine and histidine residues.

Oxyhaemoglobin which is in R state does not have the conformation to allow interaction with 2,3-BPG. The oxygen-haemoglobin dissociation curve is sigmoid shaped. 2,3-BPG selectively binds to deoxyhemoglobin and stabilises the T state, making it harder to bind to oxygen molecules and thus facilitating the release of oxygen molecules in nearby tissues.

2,3-BPG is part of a feedback loop that prevents tissue hypoxia in conditions such as high altitudes, congestive heart failure or airway obstruction. In such conditions, changing oxygen and pH levels catalyse the generation and breakdown of 2,3-BPG.

As a result, 2,3-BPG is accumulated and it facilitates rapid oxygen release in the adjacent tissues. There is a 30% increase in the intracellular formation of 2,3-BPG in pregnant women so that more oxygen can be passed on to the foetus.

Clinical Significance

1. Hyperthyroidism: According to a study in 2004, hyperthyroidism directly affects the in-vivo concentration of 2,3-DPG. The thyroid hormones stimulate the erythrocyte glycolytic activity and increase the concentration of 2,3-DPG.
2. Chronic Anaemia: In the case of chronic anaemia, red blood cells increase the concentration of 2,3-DPG by four to five times to increase the oxygen capacity of the patient.
3. Chronic respiratory disease with hypoxia: High altitude pulmonary edema has been related with low occurrence of 2,3-BPG in recent scientific studies.

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• Energetics of Anaerobic Glycolysis
• Composition of Blood and Its Functions
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• NEET MCQs on EMP pathway