2004A11 What is 2,3-DPG? How is it produced in red blood cells and how does it interact with haemoglobin?
What is its relevance in altitude exposure, anaemia and stored blood?

 

List:

·         Intro

·         Interaction with haemoglobin

·         Clinical applications

 

Intro: 2,3-DPG

What is it

·   Three carbon metabolic intermediate

·   Highly negatively charged

·   High concentration in RBC

·   Produced from 1,3-BPG (glycolytic intermediate) by the Rapoport-Luerbering shunt

Factors increasing production

1.    Hypoxia (e.g. altitude, chronic lung disease)

2.    Acidosis (inhibition of glycolysis hence ↑RL shunt)

3.    Anaemia (? causing hypoxia and acidosis)

 

Interaction with haemoglobin:

Adult Hb

·   Binds to the β-globin chain

·   Stabilises the tense (T) low affinity conformation

·   Hence right shift of oxyhaemoglobin dissociation curve (OHDC) -> ↑p50

·   Aids O2 unloading at tissue capillaries

·   Reverse at the lungs -> O2 loading

·   Effect on gas exchange vivo appears less significant than predicted

Foetal Hb

·   Serine instead of histidine at position 143 on globin chain

·   Histidine positively charged, interacts with negative charges on 2,3-DPG

·   Serine neutrally charged, does not interact

·   Hence HbF has very low affinity for 2,3-DPG

·   Left shift of OHDC, lower p50 of 19mmHg cf. 26mmHg

 

Clinical applications:

Altitude

·   ↑2,3-DPG production due to ↓PaO2

·   Right shift OHDC -> ↓O2 affinity -> ↑tissue oxygenation -> ↑EO2

·   Only partly offsets L shift caused by resp alkalosis (↓PaCO2, ↑pH)

Anaemia

·   ↑2,3-DPG production due to ? cellular hypoxia and acidosis

·   ↓affinity -> ↑tissue oxygenation -> ↑EO2

Stored RBC

·   50% ↓[2,3-DPG] at 2/52

·   95% ↓ at 4/52

·   Due to ↓temp -> ↓glycolysis and lack of substrate

·   Left shift OHDC -> ↑O2 affinity -> ↓EO2 -> tissue oxygenation

·   [2,3-DPG] restored after 24 hours

 

 

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