Lecture 12

Question 1

In which state is the haem dished?

Answer 1

Deoxygenated state

Question 2

What occurs when haemoglobin becomes oxygenated?

Answer 2

The oxygen flattens the haem, and pulls histidine F8 and helix F towards the binding site

Question 3

What weakens the oxygen binding to the haem?

Answer 3

Any other bond that pulls alpha helix F away

Question 4

What are conformational changes

Answer 4

Shifts in the orientation of a proteins secondary elements

Question 5

What can confirmational changes cause in haemoglobin?

Answer 5

The balance of T <-> R states

Question 6

What are the ways in which conformational changes can occur in haemoglobin?

Answer 6

Allosteric regulation, pH, physiological / genetic changes

Question 7

What are allosteric inhibitors

Answer 7

Compounds which can bind and stabilise the T-state, unmasking cooperativity

Question 8

What are examples of allosteric inhibitors?

Answer 8

BPG, CO2, H+

Question 9

What is stripped haemoglobin?

Answer 9

Haemoglobin which has no allosteric inhibitors

Question 10

What state is stripped haemoglobin in?

Answer 10

R-state, showing little cooperativity

Question 11

What occurs in haemoglobin in the absence of allosteric inhibitors?

Answer 11

The O2 binds too tight, increasing O2 affinity and making it hard to remove

Question 12

What is BPG?

Answer 12

An allosteric inhibitor that stabilised Hb in the deoxy T-state reducing oxygen affinity

Question 13

How does BPG bind to deoxy-Hb?

Answer 13

Through electrostatic interactions

Question 14

When is BPG produced?

Answer 14

During respiration in peripheral tissues to promote oxygen release

Question 15

What is the Bohr effect?

Answer 15

The reduction in affinity of haemoglobin for O2 in metabolising tissues with elevated CO2 and H+ leading to low pH

Question 16

What are the two components of the Bohr effect?

Answer 16

Lower pH favours the protenation of histidine residues and promotes stronger interactions in the T-state.
CO2 can bind to the animo-terminal amino group, stabilising deoxy-Hb conformation in the T state

Question 17

What is true if the Hb curve is more sigmodial?

Answer 17

The pH is lower

Question 18

What are the forms of foetal haemoglobin?

Answer 18

Beta, gamma and alpha

Question 19

What are the general forms of foetal haemoglobin?

Answer 19

2x alpha and 2x gamma

Question 20

What are the general forms of post-natal haemoglobin

Answer 20

2x alpha and 2x beta

Question 21

What is the difference between foetal and post-natal Hb oxygen affinity?

Answer 21

Foetal haemoglobin is less sensitive to BPG so, therefore, binds oxygen more tightly

Question 22

What is the difference between the beta and gamma chains in haemoglobin?

Answer 22

The gamma chain has serine residues replacing two of the His residues at the BPG binding site

Question 23

What is HbS

Answer 23

Sickle cell haemoglobin

Question 24

What is the mutation in HbS?

Answer 24

Hb beta E6V variant

Question 25

What does the mutation in HbS cause?

Answer 25

Variant enables an abnormal hydrophobic interaction between Hb tetramers which causes them to self associate into a long polymer

Question 26

Why is HbS dangerous?

Answer 26

Changes the shape of red blood cells which can cause them to get stuck in blood capillaries

Question 27

What is HbS resistant to?

Answer 27

Malaria

Question 28

What are the two possible treatments for HbS?

Answer 28

CRISPR and Vexelotor

Question 29

What does CRISPR do to HbS?

Answer 29

Gene therapy up-regulates foetal haemoglobin through a transcription factor which can turn the genes on and off

Question 30

What does Voxelotor do to HbS?

Answer 30

Stabilises the oxygenated state, increasing oxygen affinity.