Lecture 12 - O2 Transport and Storage by Haemoglobin and Myoglobin Pt. II Flashcards

1
Q

What does the haem look like in deoxyhaemoglobin?

A

dished

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens to the haem upon the formation of oxyhaemoglobin?

A

oxygen flattens the haem and pulls HisF8 and helix F toward the binding site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What will weaken oxygen binding?

A

anything that keep helix F away from the binding site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are conformational changes?

A

shifts in the orientation of protein secondary elements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are some mechanisms that work together to shift between T and R states

A
  • Allosteric regulation
  • pH
  • Physiological/genetic changes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What can change the balance of T & R state haemoglobin?

A

Conformational changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

When is co-operativity prominent?

A

In the presence of allosteric inhibitors of binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What stabilises the T-state?

A

allosteric inhibitors BPG, CO2, and H+. this allows better cooperativity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What state is ‘stripped’ haemoglobin predominantly in in the absence of inhibitors?

A

R-state, shows little co-operativity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Haemoglobin allosterically controlled by?

A

2,3 - biphosphoglycerate (BPG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does BPG bind to deoxy-Hb?

A

electrostatic interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does BPG do to Hb?

A

stabilises Hb in the deoxy T-state reducing oxygen affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is BPG produced?

A

during respiration in peripheral tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does BPG promote?

A

oxygen release where it is required

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does CO2 do to oxygen affinity?

A

reduce oxygen affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does CO2 reduce the affinity of haemoglobin for O2?

A

The Bohr effect - elevated CO2 and lower pH (higher [H+]) in metabolising tissues both reduce the affinity of haemoglobin for O2

17
Q

How does lower pH decrease oxygen binding affinity?

A

favours protonation and stronger ionic interactions in the T-state

18
Q

How does CO2 reduce oxygen binding affinity directly?

A

binds to amino-terminal amino group stabilising the deoxy-Hb conformation in T-state

19
Q

What alternate isoforms of haemoglobin does Foetal haemoglobin have?

A

zeta equivalent to alpha, epsillon, and gamme equivalent to beta

20
Q

What differs between foetal and normal haemoglobin?

A

Different amino acid sequences of normal haemoglobin subunits alter their oxygen binding properties

21
Q

Does foetal or normal haemoglobin hold oxygen tighter?

22
Q

Why can foetal haemoglobin bind oxygen more tightly?

A

It is less sensitive to BPG

23
Q

Why is foetal haemoglobin less sensitive to BPG?

A

the gamma chain replaces the beta chain in foetal Hb. The gamma chain has a serine place of a histidine in the BPG binding site.

24
Q

What causes sickle cell haemoglovin?

A

The beta E6V variant of haemoglobin

25
What is the consequence of sickle cell haemoglobin?
Sickle shape red blood cells get stuck in capillaries
26
What is one benefit of sicle cell haemoglobin?
resistance to malaria
27
What does the beta E6V variant of haemoglobin do?
enables an abnormal hydrophobic interaction between Hb tetramers
28
When is the beta E6V variant particuarly exposed?
when in the deoxy haemoglobin form, as this causes polymerisation of Hb into chains that distort the RBC's
29
How does CRISPR-based therapy treat Sickle cell disease?
Up-regulation of foetal haemoglobin replaces faulty normal haemoglobin production
30
How does Voxelotor treat sickle cell disease?
It is an oxygen affinity modulator, stabilises the oxygenated state, increases oxygen affinity