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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