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Flashcards in Myoglobin and haemoglobin Deck (31)
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2 models of O2 binding to Hb

sequential and concerted


function of myoglobin

oxygen store in muscle


function of haemoglobin

oxygen transporter in blood


haem group structure

  • 4 pyrrole rings linked together (a protoporphyrin) in a planar structure
  • Fe is constrained in the ferrous form Fe2+ (prevents Fe oxidising to Fe3+)
  • Fe must be in the ferrous Fe2+ form to enable binding of oxygen
  • Fe has six coordinate bonds - four to the haem, one to the globin and one to the O2
  • Binding of oxygen to the Fe2+ is a reversible interaction


myoglobin structure

  • Single protein molecule (monomer)
  • Protein primary structure - 150 amino acids proteins
  • Secondary structure - eight alpha-helices A-H
  • Almost no beta sheets
  • Protein fold - hydrophobic pocke


haem binding to myoglobin

  • Haem binds to histidine in helix F, position 8 (F8) in globin protein
  • A globin protein evolved with a hydrophobic pocket (many hydrophobic side chains)in which a haem group could bind (globin + haem = myoglobin)


what does His E7 in haem group do

  • distorts binding of gas molecules to 6th co-ordination position on Fe
  • The position of His E7 sterically hinders and reduces the binding affinity of oxygen (and also the respiratory poison carbon monoxide, CO, to which Mb binds much more readily than oxygen) to myoglobin


myoglobin vs haemoglobin O2 binding and release 

  • Myoglobin is O2 saturated at low pO2
  • O2 only released to muscle cells when cellular pO2 is very low
  • Hence myoglobin has evolved to function as a "backup" store of O2 in muscle cells
  • Haemoglobin functioning as an O2 transporter in blood had to evolve a much weaker binding affinity for oxygen - binds at high pO2 and releases at low pO2


haemoglobin O2 binding and release

Haemoglobin has had to evolve binding O2 less tightly because O2 must be released in peripheral tissues where myoglobin does not release it



how many oxygen molecules and atoms can bind to Hb

4 O2 molecules, 8 O atoms


Hb subunits

2 alpha and 2 beta globins


Hb binding of oxygen effect

  • Tetramer globin subunits interact (cooperate) with each other
  • Results in binding or releasing O2 progressively more easily as each subunit influences neighbouring subunits
  • Results in sigmoidal O2 saturation curve (binding one O2 makes it easier to bind the 2nd and the 3rd O2 etc)


cooperative binding of oxygen to Hb

  • Binding of O2 to one subunit of Hb tetramer induces conformational change in the subunit
  • Conformational change in transmitted to adjacent subunits which are in contact, making binding of O2 to these subunits easier


conformational change in Hb when O2 binds

  • When O2 binds to deoxy-Hb, the Fe2+ moves into the plane of the haem ring and draws the His F8 down, leading to repositioning of the F helix
  • This results in conformation change in each Hb subunit on binding to oxygen, as movement of the F helix causes a change in conformation in the rest of the protein


effect of BPG on O2 release

  • 2,3-biphosphoglycerate (BPG) fits into the bigger central cavity in deoxy-Hb and bind
  • This holds Hb in the deoxy conformation ensuring O2 releases to cells and does not re-bind to Hb
  • This effect contributes to the release of oxygen from haemoglobin at peripheral tissues where the local pO2 is relatively low and oxygen is being taken up by cells to enable aerobic metabolism
  • The relatively high pO2 at lungs displaces BPG when binding of O2 to deoxy-haemoglobin occurs


how does BPG bind to Hb

  • The binding of BPG is at a site remote from the binding sites of O2
    • Allosteric effect
  • Binds to deoxy-Hb by electrostatic interaction (-ve BPG with +ve histidine)
  • In the presence of BPG, the affinity of oxygen binding to haemoglobin is reduced significantly


effect of high CO2 conc on O2 release

  • CO2 can bind to the extreme N-terminal amino group
  • contributes to stabilising the deoxy-Hb conformation


effect of high [H+] near metabolising tissues

As [H+] increases (pH decreases) (near metabolising tissues) the oxygen binding affinity of haemoglobin is reduced (known as the Bohr effect)


foetal haemoglobin features

  • Foetal haemoglobin (HbF) has a greater affinity for oxygen than does adult haemoglobin (HbA)
  • Due to being composed of 2 alpha subunits and 2 gamma subunits rather than 2 alpha and 2 beta subunits
    • Gamma-alpha has higher affinity for oxygen
    • In gamma subunit, His143 (+ve) is replaced with Ser143 (-ve) so less electrostatic attraction to BPG (-ve)


HbS sickle cell features

  • Mutation in Hb beta subunit
  • Amino acid 6 mutated from glutamic acid (polar) to valine (non-polar)
  • When in the deoxy form, Hb aggregates to form linear polymers which distort shape of RBC's
  • some malaria resistance


Met-Hb (HbM Boston) features

  • Fe2+ is oxidised to Fe3+
  • Mutation of distal His E7 of alpha chains to Tyr displaces proximal His F8, which becomes 5th ligand, stabilising Fe3+ state


HbC Hb Christchurch

Beta subunit E15 mutated from phenylamine (large, non-polar) to serine (small, polar) so haem slightly destabilised - not too serious


sequential model of O2 binding

binding of one O2 will makes it easier for 2nd O2 to bind and stay on because there will be a conformational change in the quaternary structure when O2 binds to each subunit


concerted model of O2 binding

all subunits are always in the same configuration as each other - either T or R state. At low pO2, T state is strongly favoured and at high pO2, R state is strongly favoured


what is bohr effect

where increased CO2 level in blood results in low pH due to high H+, causing lower affinity of O2 to Hb. Causes right shift in O2 saturation curve


allosteric site

site on a protein which is not the active site, to which a regulatory molecule can bind


actual model of O2 binding

concerted with features of sequential



abnormal form of haemoglobin in which a CO molecule is bound to haem Fe2+



abnormal form of Hb in which cyanide is bound and iron is present in Fe3+ state


treating cyanide poisoning

antidote given so that met-Hb is formed. Cyanide binds to Met-Hb to form cyanomet-Hb, hence met-Hb acts as a sponge to soak up cyanide