Oxygen Transport

Question 1

What molecules can haemoglobin bind? (3)

Answer 1

Oxygen
Carbon dioxide
H+

Question 2

Where is myoglobin present?

Answer 2

Skeletal and cardiac muscle

Question 3

How many haem groups are found in a haemoglobin molecule?
How many oxygen molecules can a Hb molecule bind?

How many haem groups are found in a myoglobin molecule?
How many oxygen molecules can a myoglobin molecule bind?

Answer 3

4
4

1
1

Question 4

What is the structure of a haem group?

Answer 4

Fe2+ bonded to 4 nitrogen atoms in the centre of the ring structure

2 additional bonds can be made, 1 bond is made to a histidine residue, the other to an oxygen molecule

Question 5

What is the structure of myoglobin?

Answer 5

Single polypeptide chain

Mainly alpha-helical

Question 6

How does oxygen bind to a haem group? What change does this result in?

Answer 6

Oxygen binds to Fe atom - which usually sits below the plane of the ring
Binding of the oxygen results in Fe atom moving into the plane of the ring —> small change in protein conformation

Question 7

What type of curve does oxygen binding in myoglobin show?

Answer 7

Hyperbolic

Question 8

What type of curve does haemoglobin binding to oxygen show?

Answer 8

Sigmoidal

Question 9

What is p50?

Answer 9

The partial pressure at which there is 50% saturation of myoglobin/haemoglobin with oxygen

Question 10

What is the structure of a haemoglobin molecule?

Answer 10

4 polypeptide chains - 2 alpha and 2 beta

4 haem groups - 4 oxygen molecules

Question 11

Haemoglobin can exist in which two states?

Answer 11

T state - low affinity

R state - high affinity

Question 12

What stabilises the structure of the T state?

Answer 12

Interactions between +ve histidine and -ve aspartate residues

Question 13

Are Haem groups are more exposed in T or R state haemoglobin?

Answer 13

R state

Question 14

How does binding of oxygen promote stabilisation of the R state?

Answer 14

Binding of oxygen pulls fe into the plane of the ring of a haem group resulting in a change in conformation of the Hb molecule - interactions lost due to small rotation and haem groups more exposed for binding

Question 15

Why is the haemoglobin oxygen curve sigmoidal?

Answer 15

Due to cooperative binding of oxygen (cooperativity)

Binding affinity for oxygen increases as the number of oxygen molecules bound increases

Question 16

What does the sigmoidal binding curve for Hb suggest about the states of haemoglobin in the blood?

Answer 16

There is a mixture of Hb in the high and low affinity states

Question 17

What is the benefit of the sigmoidal curve of Hb for the body?

Answer 17

Allows haemoglobin to be more sensitive to small changes in [O2]
Loading/unloading of oxygen is more efficient

Question 18

Shifting of an oxygen binding curve to the left _________ affinity

Answer 18

Increases

Question 19

Shifting of an oxygen binding curve to the right _________ affinity

Answer 19

Decreases

Question 20

What does the binding of 2,3-bisphosphoglycerate (BPG) result in?

Answer 20

Shifts oxygen binding curve to the right
Decreases affinity of Hb to oxygen

Increases efficiency of Hb as an O2 carrier

Question 21

How does BPG bind to Hb?

Answer 21

1 molecule of BPG binds to one Hb molecule usually in the centre

Question 22

What happens to [BPG] at high altitudes? Why?

Answer 22

Increased concentration. More oxygen is released at the tissues.

Question 23

How does CO2 bind to Hb molecules?

Answer 23

Covalently bonds to n-terminus of each chain

Question 24

How do H+ ions bind to Hb?

Answer 24

They protonate -ve amino acids

Question 25

What effect does the binding of CO2 and H+ ions have on the affinity of Hb for oxygen?

Answer 25

Lowers the affinity

Question 26

How does the Bohr effect help with the supply and demand of oxygen at metabolically active tissues?

Answer 26

At metabolically active tissues ---> high [H+] | Lower affinity of Hb for oxygen ---> oxygen released at respiring tissues

Question 27

How does CO poisoning work?

Answer 27

Binds very tightly to Hb and with a higher affinity | Stopping oxygen transport

Question 28

When is CO poisoning fatal?

Answer 28

When 50% or more of the Hb is CO bound

Question 29

How does binding of CO to haemoglobin affect other subunits?

Answer 29

Increases affinity of unaffected subunits for oxygen

Question 30

What is the structure of HbA and HbF?

Answer 30

HbA = adult haemoglobin (vast majority) - 2 alpha chains, 2 beta HbF = fetal haemoglobin - 2 alpha, 2 gamma chains

Question 31

What are features of HbF?

Answer 31

Has a higher affinity than HbA for oxygen - so oxygen passes from the mother to the foetus

Question 32

Sickle cell anaemia is cause by a mutation in which gene?

Answer 32

Beta-goblin gene

Question 33

How does the mutation of glutamate to valine in the beta globin gene in sickle cell anaemia, change the structure of the haemoglobin molecule?

Answer 33

Results in the formation of a hydrophobic 'sticky' pocket

Question 34

How do sickle cell haemoglobin (HbS) interact with other Hb molecules?

Answer 34

Polymerises with other Hb molecules causing suckling of RBCs

Question 35

Sickle RBCs are more prone to ______

Answer 35

Lysis

Question 36

What are thalassaemias?

Answer 36

Group of genetic disorders resulting in incorrect proportions of alpha and beta globin chains

Question 37

What is B-thalassaemia?

Answer 37

Decreased/absent b-globin chain production

Question 38

What is a-thalassaemia?

Answer 38

Decreased/absent a-globin chain production

Question 39

Is beta-thalassaemia developed before or after birth?

Answer 39

Onset after birth

Question 40

Is alpha-thalassaemia developed before or after birth?

Answer 40

Before

Question 41

Can B-globin chains form stable tetramers?

Answer 41

Yes, with increased affinity for oxygen

Question 42

Can a-globin chains form stable tetramers?

Answer 42

No