Oxyen Transport

Question 1

What is myoglobin?

Answer 1

• a red protein containing haem , which carries and stores oxygen in muscle cells.

Question 2

Why does oxygen actually need to bind to haemoglobin in order to be transported ?

Answer 2

Because oxygen is insoluble so it cannot merely just dissolve in blood and be transported

Question 3

What does oxygen actually bind to in haemoglobin?

Answer 3

It binds to Fe2+ ions in the haem group.

Question 4

How many o2 molecules can bind to one Fe2+ ion in each haem group , in both myoglobin and haemoglobin?

Answer 4

1 molecule of o2.

Question 5

How is Fe2+ actually bound to the protein ?

Answer 5

Via a histidine residue ( proximal histidine ) on the other side of the ring

Question 6

Describe the structure of myoglobin

Answer 6

• globular protein
• compact structure
• 75% alpha helical
• single chain globular protein that consists of 153 amino acids.

Question 7

What type of graph would the binding of oxygen to myoglobin exhibit ?

Answer 7

• hyperbolic graph

- as myoglobin has a higher affinity for oxygen than haemoglobin

Question 8

Explain how myoglobin slightly changes in conformation when oxygen binds ?

Answer 8

• Fe in deoxymyoglobin is slightly below the plane of the ring , when oxygen binds it causes movement of fe into the plane of the ring .
• movement of fe causes movement of histidine F8 and a small change in overall protein conformation

Question 9

What best describes the shape of a oxygen -haemoglobin dissosiation curve ?

Answer 9

Sigmoidal

Question 10

Describe the structure of haemoglobin

Answer 10

2 alpha helical subunits ( made up of 141 amino acid residues) and 2 beta subunits (146 amino acid subunits)

• 4 polypeptide chains in total
• can bind with 4 oxygen molecules.

Question 11

What are the two states haemoglobin can exist as ?

Answer 11

• T state ( low affinity T state) - before any oxygen has bound
• high affinity R state - once oxygen has bounded to first haem group

Question 12

Why is the oxygen binding curve for haemoglobin sigmoidal ?

Answer 12

• the binding of one oxygen molecule promotes the binding of subsequent molecules because it causes a conformational change in haemoglobin from a Low affinity T state to a high affinity R state.
• this makes it easier for haemoglobin to bind to oxygen,
• this is important because if haemoglobin remained in a high affinity state all the time then oxygen would be strongly bound and there would be less oxygen being unloaded for respiring tissues,

Question 13

What are the two things that can help regulate oxygen binding ?

Answer 13

1. 2,3 bisphosphoglycerate (BOG)

2) carbon dioxide and H+

Question 14

What is the role of 2,3 biphophosphoglycerate

Answer 14

• it binds to an allosteric site on haemoglobin and works to reduce haemoglobins affinity for oxygen - this helps to regulate oxygen binding.
• it is an allosteric inhibitor

Question 15

Why do athletes tend to train at high altitudes?

Answer 15

-athletes tend to train at high altitudes because at high altitudes there is very low oxygen in the atmosphere. This promotes the increase in the concentration of Biphospholglycerate. This results in a reduced affinity for oxygen , which results in greater oxygen release to tissues.

Question 16

What is the resulting consequence of H+ and co2 binding to haemoglobin? and what is this called

Answer 16

Lowers the affinity of haemoglobin for oxygen

BOHR EFFECT

Question 17

Why is the Bohr effect important ?

Answer 17

Metabolically active tissues produce large amounts of H+ and Co2 - Bohr effect ensures the delivery of o2 is coupled to demand.

Question 18

Carbon monoxide poisoning

Answer 18

• this is where CO permenantly binds to haemoglobin and haemoglobin. This blocks oxygen transport. When 2/4 subunits are bound to carbon monoxide , it becomes lethal.

Question 19

How would we treat carbon monoxide poisoning?

Answer 19

1) blood transfusions

2) place patient in a room that has a very high pressure of oxygen.

Question 20

What are the three different forms of haemoglobin?

Answer 20

HbA : 2 alpha subunits and 2 beta subunits.

2) HbF ( foetal haemoglobin) : 2 alpha subunits and 2 gamma subunits
3) HbA2 : 2 alpha subunits and 2 delta subunits

Question 21

When is the majority of alpha subunits formed in a human ?

Answer 21

Very early development, 9 months before baby is born.

Question 22

When is the majority of beta subunits made ?

Answer 22

3 months after birth

Question 23

Why is foetal haemoglobin so important .

Answer 23

HbF is the major haemoglobin in foetal blood.

• it has a higher affinity for o2 than HbA which allows transfer of o2 to foetal blood from the mother.

Question 24

What is the cause of sickle cell anaemia

Answer 24

Missense mutation

• which results in glutamate being replaced by valine In Beta globin.
• it is now called HbS.
• glutamate is hydrophilic whereas valine is hydrophobic which results in deoxygenated HbS to interact with eachother and polymerise.
• this results is sickled cells : make prone to lyse ( anaemia )

-

Question 25

Define thalassaemias

Answer 25

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

Question 26

Describe b-thalassaemias

Answer 26

• decreases or absent B-globin chain production
• alpha chains unable to form stable tetramers
• symptoms appear after birth
• HbF begins to take over which is bad because less oxygen will actually be unloaded to respiring tissues.

Question 27

How many genes are there on each chromosome that codes for the beta-globin residues ?

Answer 27

• each copy of chromosome 11 has only ONE gene for b-globin chains

Question 28

How many genes are there on each chromosome 16 that code for alpha-globin chains ?

Answer 28

TWO adjacent genes for alpha globin chains on each chrosmome 16.

Question 29

A-thalassaemias

Answer 29

Decreased or absent a globin chain production

• several different levels of severity due to multiple copies of the alpha chains present
• beta chains can form stable tetramers with increased affinity for oxygen.
• onset after birth

Question 30

Allosteric activators shift curve to the ….. and enhance high affinity ….. state

Answer 30

Left

R state

Question 31

Allosteric inhibitors shift the curve to the …. and enhance the low affinity… state

Answer 31

• ask tutor

- T state

Question 32

What does g,glycosylation of HbA result in .. and what can the product be used to indicate ?

Answer 32

HbA1Cwhich can be used to indicate diabetes as high HbA1C indicates very high blood glucose levels

Question 33

Outline the process of glycosylation of HbA

Answer 33

When a person is hyperglycaemic , glucose attaches to haemoglobin through a process of glycosylation ( this particular process does NOT use enzymes).

• this forms HbA1C.
• once glucose is bound , it is permanently like that.
• this can be used to indicate diabetes

Question 34

What is the cause of beta thalassaemia and alpha thalassaemia?

Answer 34

• mutation in chrosomosome 11 for beta thalassaemia

- mutation in chromosome 16 for alpha thalassaemia

Question 35

How can you diagnose beta thalassaemia

Answer 35

There would be a very high concentration of HBF in the blood
And high HB A1 in the blood

Question 36

How can you diagnose alpha thalassaemia

Answer 36

Red blood cells smaller than usual