Myoglobin and Haemoglobin

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Haem

The haem(UK)/heme(USA) prosthetic group is necessary for myoglobin and haemoglobin to bind to oxygen. The difference between protoporphyrin XI and haem is a central Fe molecule.

Structure of myoglobin

It polypeptide chain is folded complicatedly so it is very compact. 75% of its amino acids are in alpha-helix with 8 major helical regions, non polar (hydrophobic groups) in the centre and polar amino acid side chains on the outside. It is water soluble.

Haemoglobin

It is made up of 4 polypeptide chains, each folded in generally the same way as myoglobin. Alpha-1 and Alpha-2 have the same amino acid sequence, Beta-1 and Beta-2 have the same amino acids sequence but different the the alpha polypeptide chains. There are no covalent bonds instead they are lonked by electrostatic interaction and hydrogen bonds. Haem groups are all in different places

The effect of oxygen concentration on binding of oxygen to haemoglobin

The Haem is anchored to the protein by bonding to the imidazole ring of a histadine side chain, in the absense of oxygen the iron atom lies slightly out of the plane of the haem ring. On binding of oxygen the iron atom moves in to the plane of the haem ring and pulls the histadine with it. It is a very small change that causes a very large change, it changes the shape of haemoglobin from T to R.

The higher affinity of haemoglobin for oxygen when outside of red blood cells

The difference in affinity between pure haemoglobin and haemoglobin in red blood cells is due to the presence of 2,3-bisphosphoglycerate in red blood cells. It reduces the affinity of haemoglobin becasue:

it only binds to deoxyhaemoglobin

one molecule of 2,3-bisphosphoglycerate binds per haemoglobin tetrmer in a pocket.

binding of 2,3-bisphosphoglycerate involves the cross-linking of 2 beta chains by electrostatic interactions. Deoxygenated haemoglobin is made more stable and oxygenation is more difficult because of the cross linking reducing affinity.

2,3-bisphosphoglycerate is lost on oxygenation becasue the binding cavity is too small.

The higher oxygen affinity of foetal than maternal haemoglobin

Foetal haemoglobin (alpha2, gamma2) binds 2,3 bisphosphoglycerate less tightly than adult haemoglobin there for has a higher affinity for oxygen.

Sickle Cell Anaemia

It is an inherited disease which is evident in homozygotes that reduces red blood cells. Anaemia results from cells becoming sickle on deoxygenation, these are fragile and blook blood vessels. Deoxygenated haemoglobin form long rods in sickle-cell anaemia.

The substitution of valine(mutant) for glutamic acid at position 6 on the beta chain of the haemoglobin generates surface hydrophobic residue which fits into the pocket of the deoxygenated beta chain allowing them to bind together and form fibres.

The Bohr Effect (pH)

Respiration causes a drop in pH this impacts oxygen binding by reducing its affinity for oxygen therefore releasing it to tissue. The Bohr effect in part involves stabilization of the protonated form of His 146. As the pH in the tissue drops due to respiration His 146 is more likely to be protonated, when this happens it can form a salt bridge with aspartate 94. The formation of a salt bridge stabilizes the T state leading to a greater tendency for oxygen to be released.