10 Myoglobin & Haemoglobin

Question 1

What is the structure of a Haem group?

Answer 1

Protoporphyrin ring and an Fe atom bound to 4 N atoms of the ring.

Question 2

How many molecules of oxygen does each haem group bind to?

Answer 2

1

Question 3

What is the structure of myoglobin?

Answer 3

Single polypeptide chain with 1 haem group that can bind 1 molecule of oxygen

Question 4

How does oxygen binding to haemoglobin or myglobin alter their structure?

Answer 4

Causes movement of Fe into the plane of the ring, causing a small change in protein conformation. More important in haemoglobin.

Question 5

What shape is the myoglobin dissociation curve?

Answer 5

Hyperbolic

Question 6

What shape is the oxygen dissociation curve of haemoglobin?

Answer 6

Sigmoidal

Question 7

Outline the structure of haemoglobin.

Answer 7

A tetramer consisting of 2 alpha, and 2 beta polypeptide chains.
4 haem groups , can bind 4 molecules of oxygen.

Question 8

How does oxygen binding alter haemoglobin?

Answer 8

It causes a structural change, which promotes stabilisation of the high affinity R state, with haem groups more exposed.

Question 9

Why is the haemoglobin binding curve sigmoidal?

Answer 9

It las low affinity for oxygen at low partial pressures (in tissues).
It has high affinity for oxygen at high partial pressures (in lungs). So it will pick up oxygen in lungs and release it in tissues.

Question 10

What does ‘cooperative binding of oxygen’ mean?

Answer 10

The binding affinity for oxygen increases as more oxygen molecules bind to Hb subunits. First O2 molecule binding is low affinity and hard, but last is high affinity and very easy.

Question 11

Which has a higher affinity for oxygen, myoglobin or haemoglobin?

Answer 11

Myoglobin

Question 12

How does 2,3 Bisphosphoglycerate (BPG) impact oxygen binding?

Answer 12

It lowers the affinity of Hb for oxygen, shifting the curve right. Allosteric inhibitor.

Question 13

Where is BPG found?

Answer 13

In red blood cells

Question 14

How many BPG molecules bind to a haemoglobin tetramer?

Answer 14

1 per tetramer

Question 15

When will BPG concentration be increased?

Answer 15

At high altitudes where they is less O2 in the atmosphere,as it promotes O2 release at the tissues.

Question 16

Which amino acid residues does BPG interact with?

Answer 16

It is negatively charged so tends to interact with positive hist and lys residues.

Question 17

Other than BPG, what else can bind to haemoglobin molecules to regulate oxygen transport?

Answer 17

Co2 and H+.

Question 18

What effect does CO2 and H+ have on haemoglobin?

Answer 18

Lowers the affinity of haemoglobin for oxygen. The bohr effect,rightward shift.

Question 19

Why is it useful that CO2 and H+ cause oxygen release to tissues?

Answer 19

Metabolically active tissues produce large amounts of H+ and CO2 (lactate in anaerobic resp)
Bohr effect ensures the delivery of oxygen is coupled with demand.

Question 20

Name 3 allosteric inhibitors of haemoglobin?

Answer 20

1. BPG
2. H+
3. Co2

Question 21

Why is carbon monoxide poisonous?

Answer 21

It has much higher affinity for Hb than oxygen does, it binds tightly and blocks oxygen transport as it doesn’t dissociate.

CO binding also increases the affinity for oxygen of the other subunits, preventing oxygen release into tissues.

Question 22

What level does carboxyhaemoglobin binding become fatal?

Answer 22

COHb > 50%

Question 23

How can you reverse carbon monoxide poisoning?

Answer 23

Physically increase O2 to very high levels.

Question 24

How is HBA1c formed and what does it indicate?

Answer 24

Glycosylation of HbA, it is a diabetes marker and indicates what glucose levels have been like over the past few weeks or months.

Question 25

How does HbF affinity for oxygen differ to haemoglobin?

Answer 25

It has a higher affinity for oxygen as it has to pick up oxygen from the maternal circulation.
Left shift.

Question 26

Why are red blood cells shape altered in sickle cell anaemia?

Answer 26

Glu6Val mutation creates a hydrophobic pocket by Val which allows HbS to polymerise.

Question 27

Sickled cell are …

Answer 27

More prone to lyse

More rigid, meaning they are more likely to block microvasculature.

Question 28

What are thalassaemias?

Answer 28

Group of genetic disorders where there is an imbalance between the number of alpha and beta globin chains.

Question 29

What is the difference between beta thalassaemia and alpha thalassaemia?

Answer 29

Beta is when there is decreased or absent beta globin chain production
Alpha is when there is decreased or absent alpha chain production

Question 30

Explain the complication of beta thalassaemias.

Answer 30

There is insufficient or absent beta globin chain production, but alpha chains cannot form stable tetramers by themselves.

Question 31

Describe why alpha thalassaemia has different levels of severity?

Answer 31

There are 4 alpha globin genes, so it depends on the number of alleles affected.

Question 32

How many beta globin genes are there?

Answer 32

2

Question 33

In alpha thalassaemia, can beta-chains form stable tetramers?

Answer 33

Yes, beta chains are able to form stable tetramers, however they have increased affinity for oxygen, so are less able to release it into the tissues.

Question 34

When are you most likely to pick up alpha and beta thalassaemia ?

Answer 34

Alpha - onset before birth

Beta- after birth