Oxygen transport 13

Question 1

Where is haemoglobin found?

Answer 1

Erythrocytes in the blood

Question 2

Where is myoglobin found?

Answer 2

Heart and skeletal muscle cells

Question 3

Why does oxygen need to be transported via haemoglobin?

Answer 3

It is non-polar, not very soluble in water and stable, so it couldn’t be transported efficiently without it

Question 4

What is the function of myoglobin?

Answer 4

It is a temporary store for oxygen, and transports oxygen from the erythrocytes to the mitochondria of muscle cells

Question 5

What is haemoglobin called when it is bound to carbon dioxide?

Answer 5

Carbaminohaemoglobin

Question 6

What is the structure of a haem group and how does oxygen bind to it?

Answer 6

A protoporphyrin ring with Fe at its centre, connected to 4 N atoms of the ring. This Fe can make 2 additional bonds to oxygen, one above and one below the ring

Question 7

How does oxygen bind to the haem group in myoglobin and haemoglobin?

Answer 7

The Fe atom in the haem group is bound to the rest of the protein via a histidine residue on one side of the protoporphyrin ring, so the Fe can only form one bond with an oxygen molecule

Question 8

What level of protein structure does myoglobin have?

Answer 8

Tertiary, as it is only made up of one subunit

Question 9

What are some features of myoglobin structure?

Answer 9

It is a small protein, it is compact and globular, it is 75% α-helical (secondary structure)

Question 10

Where is the Fe located in myoglobin?

Answer 10

His 93 in the 8th α-helix

Question 11

How is Fe bound in myoglobin and haemoglobin?

Answer 11

Via covalent bonds to N atoms

Question 12

What happens when oxygen binds to the haem in myoglobin and haemoglobin?

Answer 12

It causes the movement of Fe from slightly below the plane of the ring into the plane of the ring, causing movement of the histidine and a small change in overall protein conformation. This doesn’t have much effect in myoglobin but it does in haemoglobin.

Question 13

What type of oxygen dissociation curve would a graph of oxygen saturation (y) vs partial pressure of oxygen (x) in myoglobin show? What about in haemoglobin?

Answer 13

Myoglobin - hyperbolic
Haemoglobin - sigmoidal
(1)

Question 14

What is the quaternary structure of haemoglobin?

Answer 14

Formed of 4 polypeptide chains; two α and two β subunits. Each subunit has a haem group, and is very similar in conformation to myoglobin

Question 15

What are the two states haemoglobin can exist in?

Answer 15

T state - low affinity for oxygen as haem groups are less exposed, there is larger lumen in centre of protein
R state - high affinity for oxygen as haem groups are more exposed, there is smaller lumen in centre of protein

Question 16

What effect does oxygen binding to a haem group have in haemoglobin?

Answer 16

It promotes a conformational change, changing the protein from a T state to an R state and so increasing the affinity for oxygen of the other haem groups, resulting in a sigmoidal binding curve as the binding affinity changes with the curve

Question 17

Why is the oxygen binding curve for haemoglobin sigmoidal?

Answer 17

Oxygen binds cooperatively, so its binding affinity increases as more oxygen molecules bind to Hb subunits, since the more oxygen are bound to the Hb the more exposed the other haem groups are

Question 18

Can you explain this diagram? (2)

Answer 18

(3)

Question 19

What effect does 2,3-bisphosphoglycerate (BPG) have on oxygen binding?

Answer 19

One BPG molecule binds per tetramer, and its negatively charged parts bind to the positive parts of haemoglobin, sitting in the ‘hole’ in the centre, making the haemoglobin less flexible and lowering its affinity for oxygen

Question 20

How is oxygen binding of haemoglobin affected at high altitudes?

Answer 20

At high altitudes, BPG concentration increases, promoting oxygen release at tissues as they need more of it, so the BPG shifts the curve to the right to lower oxygen affinity

Question 21

At what concentration is BPG usually present at in erythrocytes?

Answer 21

～5mM

Question 22

Describe the BOHR effect

Answer 22

H+ and CO2 an both bind to haemoglobin, and when they do they lower its oxygen affinity. This is because when you exercise lactate (acidic) is produced, so your tissues need you to release more oxygen from the haemoglobin, therefore shifting the curve to the right as pH decreases

Question 23

Why is CO so dangerous? How do you treat CO poisoning? At what percentage of COHb is it fatal?

Answer 23

It binds 250x more readily than oxygen, as it binds to the Hb
Put the patient in a hyperbaric chamber to increase pO2, so it competes with the bound CO
50%

Question 24

Which haemoglobins are found in a normal adult?

Answer 24

HbA - ⍺2β2 - 90%
HbF - α2γ2 - <2%
HbA2 - α2δ2 - 5%

Question 25

What can happen to the haemoglobin of a diabetic?

Answer 25

The α2β2 type, HbA, can get glycosylated if a lot of glucose is present in the blood, forming HbA1c, which is a way of monitoring diabetics as this stays in the blood for around 60 days

Question 26

Which chromosomes are the α- and β-globin-like genes found on?

Answer 26

16 and 11, respectively

Question 27

What is HbF? Why is it important?

Answer 27

HbF (α2γ2) is the major Hb found in foetal blood. It has a higher binding affinity for oxygen than HbA (maternal) which allows transfer of oxygen to the foetal blood supply from the mother

Question 28

What type of mutation causes sickle cell anaemia?

Answer 28

Missense mutation (glutamate to valine in β globin (HbS))
Valine causes a 'sticky' hydrophobic pocket to form, allowing deoxygenated HbS to polymerise to form bigger complexes

Question 29

How does sickle cell anaemia affect the erythrocytes?

Answer 29

Sickled cells are more prone to lyse (anaemia), and are more rigid so they can block small blood vessels

Question 30

What are thalassaemias?

Answer 30

A group of genetic disorders where there is an imbalance of α and β globin chains.

Question 31

Describe α-thalassaemias

Answer 31

Decreased or absent α chain production
Several different level of severity due to the multiple copies of α-chains present
Onset before birth
β-chains can form stable tetramers with increased affinity for oxygen

Question 32

Describe β-thalassaemias

Answer 32

Decreased or absent β chain production
α chains unable to form stable tetramers
Symptoms appear after birth

Question 33

What are allosteric effectors and inhibitors in terms of oxygen binding curves?

Answer 33

Activators shift curve to the left, promoting high oxygen affinity R state.
Inhibitors shift curve to the right, promoting low oxygen affinity T state