Myoglobin and Hemoglobin
Myoglobinis a relatively small monomeric protein that facilitates the diffusion of oxygen in
Responsible for supplying oxygen to muscle tissue in reptiles, birds, and mammals.
Hemoglobin is a larger tetrameric protein that carries oxygen in blood.
Heme prosthetic group
Both myoglobin and hemoglobin contains a heme prosthetic group.
*Prosthetic group is a protein-bound organic
molecule essential for the activity of the
Heme consists of a tetrapyrrole ring
system (protoporphyrin IX) complexed with
The four rings of this system are
linked by methene (-CH=) bridges
The unsaturated porphyrin is
highly conjugated (joined) and planar.
The iron of heme group is a ferrous iron (Fe2+) which is caged inside the porphyrin ring.
This ferrous iron can form a complex with up to 6 ligands around it when
myoglobin/hemoglobin is oxygenated and usually with 5 ligands when in deoxygenated form:
- 4 ligands are the N atoms- each N is from 1 pyrrole ring. (These are in the same plane)
The coordinated nitrogen atoms help prevent conversion of the heme iron to the ferric
state. (restricts accessibility of heme)
- The fifth ligand is an imidazole nitrogen of the proximal His-93 or His-F8. (This bond is
perpendicular to the porphyrin ring)
- The sixth ligand is oxygen. (In deoxymoglobin/deoxyhemoglobin, oxygen is not present so
iron only binds to 5 ligands) . (This bond is perpendicular to the porphyrin ring) Out of 4 sides of the porphyrin ring, the one with propionate side chain ended with the ionized
carboxyl groups is hydrophilic and thus reach into the aqueous solution (outside of the
The other 3 sides are nonpolar methyl and vinyl group (-CH=CH2) which are hydrophobic and
therefore extend into the hydrophobic interior of the polypeptide.
The whole heme group is in a hydrophobic cleft or pocket formed by three alpha helices and
two loops of the polypeptide.
The binding of the porphyrin moiety to the polypeptide is due to number of weak interactions
including hydrophobic interactions, van der Waals forces, hydrogen bonds.
The ferrous iron is coordinated to the imidazole nitrogen of His-93. (It offers 2 electrons for this
bond while N offers none)
The non-polar side chain of Val-68 and Phe-43 also contributes to the hydrophobicity of the
Help to hold theheme in place and also sterically hinder any molecules that are not oxygen
trying to bind to heme.
Myoglobin is a relatively small molecule with 153 amino acid
¾ of its amino acids involve in 8 alpha helices. These 8 alpha helices are connected by short, disordered coils.
Myoglobin is a member of the all-alpha category.
The interior of myoglobin is made up of hydrophobic amino acid residues like Val, Leu, Iso, Phe,
The surface of myoglobin is made up of both hydrophilic and hydrophobic residues.
The tertiary structure of myoglobin is stabilized by hydrophobic interactions within the core.
Is more complex than myoglobin
because it is a multisubunit protein.
Hemoglobin is a tetramer composed of 2
alpha subunits and 2 beta subunits.
These subunits face one another across
a cavity in the center of the molecule.
Each subunit contains a heme so
theoretically hemoglobin can bind four
molecule of oxygen.
The alpha subunit contains 7 helices
while the beta subunit contains 8 helices.
Each subunit especially the beta
subunit is quite alike/almost
However, hemoglobin is not simply a tetramer of myoglobin: there is an extensive interaction
between alpha and beta subunits in the quaternary structure of hemoglobin reflecting that
hemoglobin is actually a dimer of alpha-beta subunits.
This characteristic is responsible for the oxygen-binding property of hemoglobin which is
different from that of myoglobin.
The way oxygen binds to free heme and to heme in
Free heme binds irreversibly to oxygen in aqueous solution: oxidizing Fe2+ to Fe3+:
2+ 3+ -
Fe + O -> F2 + O 2
Oxidation of Fe2+ is resulted from the no steric environment in free heme. (the usual
polypeptide chain of myoglobin/a subunit of hemoglobin is not found)
The binding of oxygen to myoglobin/ a subunit of hemoglobin is not an oxidation process but
rather an oxygenation process. Oxygenation only partially oxidizes the Fe2+ ion of the heme group by temporarily giving it one
electron instead of permanently giving one electron like in oxidation.
The structure of myoglobin/hemoglobin prevents the permanent transfer of an electron:
The globin crevice/ sterically hindered hydrophobic pocket in which the heme is located
prevents complete oxidation and enforces the return of the electron to the ferrous iron
when Oxygen dissociates.
The abnormal version of hemoglobin where the ferrous iron in the
heme prosthetic group of one or all peptide subunits is converted
to ferric iron hence losing its oxygen binding property.
The conversion involves a complete oxidation of ferrous iron by
permanently transferring one of its electrons to another substance.
(This substance is being reduced)
Methemoglobin cannot function as an oxygen carrier like normal
Methemoglobin is caused by either decomposition of the blood or
by the action of various oxidizing drugs or toxic agents.
Met-Hb can bind to water. Oxygen binding curve for Hemoglobin and Myoglobin
Oxygen binding curve describes the differences between hemoglobin and myoglobin on
reversible binding of oxygen to the heme group.
The fractional saturation of myoglobin or
hemoglobin is the fraction of the total number of
molecules that are oxygenated.
Y= [MbO ]/2[MbO ]+[2b]}
In this figure on the left, the fraction saturation (Y)
of a fixed amount of protein is plotted against the
concentration of oxygen (measured as the partial
pressure of gaseous oxygen, pO ) 2
1. The oxygen-binding curve of myoglobin is hyperbolic .
There is a single equilibrium constant for the binding of oxygen to the macromolecule.
(Recall the g