O2 binding proteins Flashcards
2 main oxygen storage proteins
Haemoglobin - blood
• a tetramer
• O2 transport from lungs
Myoglobin - muscle
• a monomer
• O2 storage in tissues
What is the porphyrin ligand?
- found in haem group
- contains Fe(II) centre
- flat, unsaturated, conjugated molecule
- tetradentate ligand
- aromatic (26 pi electrons) w/ many resonance forms
Characteristics of the substituents of the porphyrin ligand
Substituents are:
• bulky
• negatively charges
• hydrophilic
What is meant by the Co-operativity of Haemoglobin
- once one O2 is bound, conformational change occurs which makes it easier for uptake of second O2
- co-operativity is lost if Hb is broken down into monomers
- when one O2 is lost, successive O2 are lost more easily
Where do metals bind in porphoryn ligands?
Bind to vacant coordination sites on the metal centre
Describe the structure of the haem group in terms of the porphoryn ligand
• contains a haem group
• haem group has 2 propanato groups attached to the porphyrin ring
(propanoate ion C2H5COO-)
• also have methyl and vinyl substituents
What is a propanato group
A propanoate ion (C2H5COO-)
What amino acid in haem group in myoglobin helps in structure?
Histidine side chain containing imidazole group
What is the function of the histidine in myoglobin haem?
Histidine side chain (containing imidazole group) holds the haem group to the protein chain
The O2 binding site on myogobin
- O2 coordinates trans to histidin group
* crowding of coordination site only allows very small molecules to have access to Fe2
Kh of haemoglobin
Kh= [HbO2]/[Hb][O2]^2.8
• the 2.8 exponent results from cooperativity - binding of o2 molecules are not independent
Why is cooperativity important in oxygen transport?
- this ensure Hb is fully loaded at lungs and fully unloads in o2 deprived environments
- in oxygen-rich environments, eg lungs, the heamoglobin is fully loaded
What would happen if cooperativity didnt exist?
Suffer asphyxiation - would not be able to carry enough o2 around body
Why are respiratory pigments needed?
O2 is not very soluble in blood therefore Hb is needed for its transport
Describe the structure of heamoglobin in its deoxy form
- in the deoxy form, Fe(II) ion is too big to sit IN the N4 plane of porphyrin
- the Fe(II) ion sits below the plane of the four porphyrin N atoms
- Fe-N (porphyrin) bond distances ~ 2.18 Å
Describe what happens when O2 binds to the haemoglobin
- when O2 binds to Fe(II) centre, the d electrons of Fe(II) are redistributed in a manner that makes the Fe(II) centre smaller
- Fe(II) ion sits within the plane of the porphyrin nitrogen atoms
- Fe-N bond distance reduced by ~ 2.00Å
What is the ultimate results of the binding of oxygen on haemoglobin?
- the movement on Fe(II) causes the histidine group to move with it
- causes a significant conformational change in the whole protein
- change results in the increased affinity for subsequent O2 binding
Why is exposure to CO dangerous?
• CO competes more effectively than O2 for the vacant site on the Fe centre
Compare the binding of O2 and CO with haemoglobin
- CO is linear (180) and binds in an end-on manner
- leads to steric clash between CO and surrounding protein chain
- O2 has a significant bend at the co-ordination O atom
- no steric clash with the surrounding protein
What is the effect of the steric clash with CO binding?
- Steric clash diminishes its binding ability but it still competes for the haem site
- but it still competes for the haem site more effectively than O2
What is the Bohr effect?
- Oxygen is released from Hb wherever the CO2 conc is high
- high [CO2] means low pH (more H+)
- CO2 + H2O –> H+ + HCO3-
Haemoglobin colour
Deoxy: bluish purple colour
Oxy: red colour
- blue colour is indicative of hypoxia
- veins have a characteristic blue-purple colour
What is the purpose of high altitude training
- training at high altitude leads to an increase in RBCs
* when athlete returns to normal altitude - has extra oxygen carrying potential
Why are Cd and Hg very toxic if available?
- Zn2+ occur at catalytic sites of many enzymes
* Cd2+ and Hg2+ can displace Zn2+ —-> dead enzymes
Oxidation number of Zn
Exhibits only one oxidation state - 2+
Zinc complexes
- no strong stereochemical preferences - can switch bw co-ordination numbers
- commonly - 4,5, and 6
Describe the bio-availability of Zn, Cd, and Hg
- Zinc: soluble and available as Zn2+
- cadmium: soluble but not as abundant as Zn
- Mercury: seems unavailable but is present naturally in the biosphere
How does Hg seem unavailable, but is present naturally in the biosphere?
- sulfolytic bacteria ‘eat’ metal sulfide ores containing S2- ion as an energy source
- HgIIS2- –> S + 2e + Hg2+ (released into the environment)
