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

Nature

·  Three carbon metabolic intermediate

·  Highly negatively charged

·  High concentration in RBC

Pathway

Increased if

·  High altitude

·  Chronic lung disease

·  Anaemia

 

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 very low affinity for 2,3-DPG

·  Left shift of OHDC, lower p50 (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

·  ↓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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