O2 binding proteins

Question 1

2 main oxygen storage proteins

Answer 1

Haemoglobin - blood
• a tetramer
• O2 transport from lungs

Myoglobin - muscle
• a monomer
• O2 storage in tissues

Question 2

What is the porphyrin ligand?

Answer 2

• found in haem group
• contains Fe(II) centre
• flat, unsaturated, conjugated molecule
• tetradentate ligand
• aromatic (26 pi electrons) w/ many resonance forms

Question 3

Characteristics of the substituents of the porphyrin ligand

Answer 3

Substituents are:
• bulky
• negatively charges
• hydrophilic

Question 4

What is meant by the Co-operativity of Haemoglobin

Answer 4

• 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

Question 5

Where do metals bind in porphoryn ligands?

Answer 5

Bind to vacant coordination sites on the metal centre

Question 6

Describe the structure of the haem group in terms of the porphoryn ligand

Answer 6

• contains a haem group
• haem group has 2 propanato groups attached to the porphyrin ring
(propanoate ion C2H5COO-)
• also have methyl and vinyl substituents

Question 7

What is a propanato group

Answer 7

A propanoate ion (C2H5COO-)

Question 8

What amino acid in haem group in myoglobin helps in structure?

Answer 8

Histidine side chain containing imidazole group

Question 9

What is the function of the histidine in myoglobin haem?

Answer 9

Histidine side chain (containing imidazole group) holds the haem group to the protein chain

Question 10

The O2 binding site on myogobin

Answer 10

• O2 coordinates trans to histidin group

* crowding of coordination site only allows very small molecules to have access to Fe2

Question 11

Kh of haemoglobin

Answer 11

Kh= [HbO2]/[Hb][O2]^2.8

• the 2.8 exponent results from cooperativity - binding of o2 molecules are not independent

Question 12

Why is cooperativity important in oxygen transport?

Answer 12

• 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

Question 13

What would happen if cooperativity didnt exist?

Answer 13

Suffer asphyxiation - would not be able to carry enough o2 around body

Question 14

Why are respiratory pigments needed?

Answer 14

O2 is not very soluble in blood therefore Hb is needed for its transport

Question 15

Describe the structure of heamoglobin in its deoxy form

Answer 15

• 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

Question 16

Describe what happens when O2 binds to the haemoglobin

Answer 16

• 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

Question 17

What is the ultimate results of the binding of oxygen on haemoglobin?

Answer 17

• 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

Question 18

Why is exposure to CO dangerous?

Answer 18

• CO competes more effectively than O2 for the vacant site on the Fe centre

Question 19

Compare the binding of O2 and CO with haemoglobin

Answer 19

• 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

Question 20

What is the effect of the steric clash with CO binding?

Answer 20

• 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

Question 21

What is the Bohr effect?

Answer 21

• Oxygen is released from Hb wherever the CO2 conc is high
• high [CO2] means low pH (more H+)
• CO2 + H2O –> H+ + HCO3-

Question 22

Haemoglobin colour

Answer 22

Deoxy: bluish purple colour

Oxy: red colour

• blue colour is indicative of hypoxia
• veins have a characteristic blue-purple colour

Question 23

What is the purpose of high altitude training

Answer 23

• training at high altitude leads to an increase in RBCs

* when athlete returns to normal altitude - has extra oxygen carrying potential

Question 24

Why are Cd and Hg very toxic if available?

Answer 24

• Zn2+ occur at catalytic sites of many enzymes

* Cd2+ and Hg2+ can displace Zn2+ —-> dead enzymes

Question 25

Oxidation number of Zn

Answer 25

Exhibits only one oxidation state - 2+

Question 26

Zinc complexes

Answer 26

• no strong stereochemical preferences - can switch bw co-ordination numbers
• commonly - 4,5, and 6

Question 27

Describe the bio-availability of Zn, Cd, and Hg

Answer 27

• Zinc: soluble and available as Zn2+
• cadmium: soluble but not as abundant as Zn
• Mercury: seems unavailable but is present naturally in the biosphere

Question 28

How does Hg seem unavailable, but is present naturally in the biosphere?

Answer 28

• sulfolytic bacteria ‘eat’ metal sulfide ores containing S2- ion as an energy source
• HgIIS2- –> S + 2e + Hg2+ (released into the environment)