Haemoglobin

Question 1

What is the Haem of haemoglobin?

Answer 1

is essentially an iron complex (Fe2+) that is required for oxygen binding. It is NOT part of the polypeptide chain, but is tightly bound by protein. The iron group is help in position by four nitrogens and the Fe 2+ can therefore make 2 more bonds

Question 2

Describe the structure of myoglobin

Answer 2

it is a protein 75% alpha helices- with a hydrophilic exterior and a hydrophobic interior (except histidines E7 and F8 )

Question 3

Where does the haem sit in myoglobin?

Answer 3

it sits in a crevice near the surface lined with non-polar residues

Question 4

Describe the interacts of the haem with the histidine residues

Answer 4

the proximal histidine (F8) bonds directly to the iron

hte distal hisitidine (E7) - plays a steric role, not actually bonded

Question 5

Oxygenation has what effect on the haem iron?

Answer 5

oxygenation moves the haem iron which moves the His F8

*this causes a domino effect- the whole haem changes conformation*

Question 6

Does myoglobin or haemoglobin have a higher affinity for O2?

Answer 6

Myoglobin - it acts as a storage for O2 so this makes sense

Question 7

What are the functions of haemoglobin?

Answer 7

transports O2 to tissues

transports CO2 and protons away from tissues

Question 8

What haemoglobin types are expressed at each stage of life?

Answer 8

embryonic = Hb Gower 1, Hb Gower 2, and Hb Portland

fetal = HbF

Minor Adult form = HbA2

Adult form = HbA

*they all differ in their peptide chain conformations*

Question 9

What sort of curve does O2 binding to Haemoglobin represent? Why is this significant?

Answer 9

sigmoidal curve - represents co-operative binding or cross talk between protein subunits

Question 10

does Hb dissociate at a higher or lower partial pressure than Mb?

Answer 10

Haemoglobin dissociates at a higher partial pressure than myoglobin -this allows for delivery of O2 from Hb to Mb

Question 11

What does co-operative binding mean?

Answer 11

co-operative binding means that the binding of one O2 to one haem group increases the affinity of remaining haem groups - allows haemoglobin to deliver more O2 than if four sites independently bound to it

Question 12

What structurally occurs when haemoglobin is oxygenated?

Answer 12

unoxygenated = tense form (T form b/c more ionic bonds), where there is a low affinity for O2 - travels back to the lungs in this state

oxygenated = relaxed form (R form some ionic bonds are broken) where the haemoglobin has a high affinity for Oxygen- enters circulation and delivers oxygen to the cells

Question 13

what prompts an oxygenated haemoglobin to release its O2?

Answer 13

the O2 partial pressure in the tissues is MUCH lower than in the lungs, and this decreases the Hb affinity for the O2, making it release it’s oxygen and return to it’s T form

Question 14

What is the Bohr effect? What does it have to do with haemoglobin?

Answer 14

the bohr effect states- O2 is released more easily at low pH or increased partial pressure of CO2- this allows haemoglobin to release oxygen exactly where it is needed (b/c cells release CO2 in respiration which decreases the pH)

This lower pH also protonates some histidines on the Hb- promoting formation of salt bridges in the T form of Hb

Question 15

What effect does 2,3 Bisphosphoglycerate have on Hb?

Answer 15

2,3 BPG is a byproduct of glycolysis - signals that a cell requires more oxygen - therefore it binds to the DEoxyHb, decreasing its affinity for O2 and stabilizing the T formation

How? - the 2,3BPG forms salt bridges with postiively charged histidine residues. - note that these are broken when the Hb is oxygenated

Question 16

If 2,3 BPG concentrations are elvated, what happens to the deliver of O2 in the tissue?

Answer 16

it increases delivery of O2 in the tissues