Haemoglobin Flashcards
Red blood cell function
- transfer O2 from lungs to tissue
- transfer CO2 from tissue to lungs
Where is myoglobin found?
skeletal and heart muscle
Myoglobin function
- facilitates rapidly respiring muscle tissue
- increases oxygen solubility
- facilitates oxygen diffusion
Myoglobin structure
- haem with 2 His residues
Histidine
- imidazole side chain
- pKa = 6
- protonated below pH6
- common in catalytic sites & metalloproteins
Globin gene family
- encode haemoglobin
- different globin genes expressed during development which alter oxygen affinity of embryonic and foetal Hb
- globins synthesised in polyribosomes
Where are haem groups systhesised?
mitochondria
Haemoglobin structure
- tetramer with 2 alpha and 2 beta subunits
- each subunit has a Haem
Haem
- centralised Fe atom
- carries oxygen
heterocyclic porphyrin derivative - protoporphyrin IX
Fe in haemoglobin
must be Fe(II) to bind oxygen
Methemoglobin
- Hb with Fe(III) -can’t bind oxygen
- usually 1-2% of Hb; over that it becomes dangerous
- increase can be caused by benzocaine, nitrites, arsine
deoxyHb structure
domed
oxyHb
planar
BPG (DPG)
- modulates Hb affinity for oxygen
- provides control and potential for adaptation (eg altitude)
- allosteric effector
Hb cooperativity
positive - sigmoidal curve
Hb-oxygen dissociation curve depends on:
[BPG] - only has effect on oxygen release and not binding
pH
Hb structure
CO2 in red blood cells
Hb-O2 curve shift to left
oxygen given up less readily
- low BPG
- HbF
Hb-O2 curve shift to right
easy oxygen delivery
- high BPG
- high [H]
- high [CO2]
- HbS
Picket fence Fe(II)-porphyrin complex with bound oxygen
- O2 binds to 6th ligand of Fe(II) out of haem plane
- 5th ligand is a His, F8 on side across the haem plane
- His F8 binds to proximal side
- Oxygen binds to distal side
oxy vs deoxy Hb
major structural differences between quaternary conformations
T –> R shift
O2 changes electronic state
Fe moves into plane dragging proximal His, which tilts and drags F helix
when can proximal His move?
when movement is accompanied by F helix translation across haem plane
When does F helix translation occur
with quaternarT - y shift that steps he a1C-b2FG contact one turn along the a1C helix.
bonds in Hb
H-bonds, salt bridges
Bohr effect
pH shift
- higher pH promotes tighter O2 binding
- lower pH permits easier release of O2 from Hb
pO2 in lungs vs capillaries
lungs - high
capillaries - low
Cl- effect
Hb affinity for O2
T - state Hb
stabilised by H-bonds
Sickle cell anaemia
genetic disease glu6 –> val
aggregation of Hb
low O2 supply to tissues
pain, organ damage, stroke, increased
