2010B15 Explain the role of haemoglobin as a buffer.

 

List:

·         Intro: Hb, buffer

·         Hb buffering mechanism

·         Hb buffering efficiency

 

Intro:

Haemoglobin

·  Specialised O2 carrying protein in RBCs

·  4 x Haem: protoporphyrin ring and Fe2+

·  4 x Globin polypeptide chain (2α, 2β)

·  Important buffer in ECF

Buffer

·  Substance resisting ↓/↑ pH when acid/base added to solution

·  = weak acid and conjugate base

·  i.e. H+ + B- <-> HB

Effective buffer

·  Abundant

·  Rapid

·  pKa near prevailing pH (+/- 1)

·  Open-ended (i.e. carbonic acid system – CO2 excreted by lungs, HCO3- and H+ by kidneys)

 

Hb buffering mechanism:

Diffusion

·  Gases pass down partial pressure gradients

·  O2: RBC -> tissue

·  CO2: tissue -> RBC

H+ buffering

·  CO2 + H2O -> H+ + HCO3- (catalysed by carbonic acid)

·  H+ + KHb <-> HHb + K+ (pKa 6.8)

·  Active component is imidazole groups of histidine residues

·  HCO3- exchanged for Cl- across the RBC membrane (=Hamburger effect)

Carbamino formation

·  -NH2 + CO2 <-> -NHCOO- + H+

·  i.e. binds to terminal amino groups and amino groups on side chains of arginine and lysine

·  H+ buffered as above

Haldane effect

·  DeoxyHb takes up more H+ and CO2

·  Minimises ↓pH from arterial (7.44) to venous (7.36) despite large ↑n(H+)

·  70% of effect: due to 3.5x ↑formation of carbaminoHb

·  30% of effect: imidazole pKa 6.6 -> 8.2 hence ↑buffering

·  For every mmol O2 unloaded, 0.7mmol H+ is loaded without ↓pH (= isohydric buffering)

(note: reverse changes occur at the lungs, facilitating O2 uptake and CO2 excretion)

 

Hb buffering efficiency:

High quantity

·  High [Hb] (140g/L) (cf. plasma proteins 70g/L)

·  Large number imidazole groups per Hb (39) (cf. plasma proteins 13)

pKa near pH

·  pKa 6.8 (oxyHb 6.6, deoxyHb 8.2)

·  pH 7.34-7.45

Open-ended

·  Indirectly via link to carbonic acid system

Rapid

·  CO2 lipid soluble, rapidly enters RBC

·  Carbonic anhydrase very fast (10,000x / second)

 

 

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