30 - Haemoglobin

Question 1

Proportion of RBC dry weight is haemoglobin?

Answer 1

97%

Question 2

Proportion of body CO2 carried by haemoglobin

Answer 2

~15%

Question 3

How is variable sigmoid binding of haemoglobin achieved?

Answer 3

Subunit co-operativity, allosteric effectors

Question 4

How do foetal and adult haemoglobins differ?

Answer 4

Foetal has alpha and gamma subunits, adult has alpha and beta subunits

Question 5

Proportion of O2 needs that would be met by diffusion

Answer 5

~1%

Question 6

Why does O2 need a carrier in the blood?

Answer 6

Deliver more O2 to tissues.

O2 extremely reactive, so need to stop it reacting with body tissues without control

Question 7

Part of haemoglobin that binds O2

Answer 7

The haem prosthetic group, NOT the protein

Question 8

Iron ion in haem

Answer 8

Iron II

Question 9

Number of coordinating positions on haemoglobin Fe2+

Answer 9

Six

Question 10

What in haemoglobin co-ordinates with Fe2+?
1)
2)
3)

Answer 10

1) Four co-ordination positions with N in porphyrin ring
2) Fifth bond to histidine F8 (8th histidine of helix F)
3) 6th bond unoccupied in deoxygenated Hb. Oxygen bonds here in oxygenated Hb

Question 11

Angle at which O2 binds Fe2+ in Hb

Answer 11

120 degrees

Question 12

Example of other things that Fe2+ haem prosthetic group is involved in

Answer 12

E- transport, EG: Cytochrome C in electron transport chain

Question 13

Colour of oxygenated Hb

Answer 13

Scarlet red

Question 14

Colour of deoxygenated Hb

Answer 14

Dark red, appears blue through skin

Question 15

Colour of HbCO (carbon monoxide)

Answer 15

Cherry red

Question 16

Colour of MetHb

Answer 16

Old Hb with Fe3+ (oxidised)

Dark brown

Question 17

Tissue that has myoglobin in it

Answer 17

Muscle

Question 18

Difference in saturation curves against partial pressure of oxygen between haemoglobin and myoglobin

Answer 18

Myoglobin has a hyperbolic curve.
Haemoglobin has a sigmoidal curve.
Myoglobin has the higher affinity for O2

Question 19

Saturation of Hb in lungs

Answer 19

90%

Question 20

Saturation of Hb in venous blood

Answer 20

64% saturated

Question 21

Difference in Hb and Mb structure

Answer 21

Hb is tetrameric, Mb is monomeric.

Share 50% of structure.

Question 22

Tertiary structure of Mb

Answer 22

Eight alpha helices

Question 23

Where does haem bind in myoglobin?

Answer 23

Between helices F and E

Question 24

P50

Answer 24

Partial pressure of oxygen that gives Hb or Mb 50% saturation with O2

Question 25

Alpha and beta subunit homology in Hb

Answer 25

50%

Question 26

Things that alter Hb affinity for O2

Answer 26

O2 binding, CO2 concentration, pH, 2,3-bisphosphoglycerate concentration

Question 27

Why don’t two alpha subunits, or two beta subunits of Hb join together?

Answer 27

Have higher affinity for other subunit than for subunits of the same type

Question 28

How does O2 binding affect Hb structure?

Answer 28

O2 binding pulls Fe2+ into same plane as the porphyrin ring. Histidine F8 is pulled, which changes conformation of entire protein.

This leads to a shift from deoxy (tense) state to osygenated (relaxed) state.

Question 29

Change between tense and relaxed state of Hb
1)
2)
3)
4)
5)
6)

Answer 29

1) Fe2+ pulled into middle of porphyrin ring.
2) Histidine on F8 helix moved.
3) Alpha and beta subunits pull past each other, rotate.
4) Electrostatic bonds are broken
5) H-bonds between alpha and beta subunits reorganise
6) If BPG is attached to deoxy Hb, it is released

Question 30

Function that O2 serves i nHb conformational change

Answer 30

Homotropic allosteric modulator

Question 31

P50 of Hb

Answer 31

26 Torr

Question 32

Heterotrophic allosteric effector of Hb

Answer 32

2,3-bisphosphoglycerate

Question 33

2,3-BPG function

Answer 33

Product of glycolysis in RBCs particularly.
Has negative charge, enters positively-charged groove between beta subunits of Hb, stabilises deoxygenated Hb.
Increases O2 unloading from Hb

Question 34

How is CO2 transported in Hb?

Answer 34

On amino terminal groups of deoxy Hb as carbamate

Question 35

How is CO2 delivered to the lungs from Hb?

Answer 35

Oxygenated Hb binds CO2 less readily than deoxygenated Hb. When Hb binds O2, releases CO2 (EG: in lungs)

Question 36

How is most CO2 transported in the blood?

Answer 36

CO2 converted to HCO3- by carbonic anhydrase, which is soluble in plasma

Question 37

Bohr effect

Answer 37

H+ binding to Hb reduces affinity for O2.
When CO2 converted to HCO3- by carbonic anhydrase, increases number of protons binding Hb, therefore O2 is dumped in low-pH tissue.

Hb also transports ~40% of protons back to lungs and kidneys

Question 38

HbF properties

Answer 38

Gamma subunit has higher O2 affinity, so can pull O2 out of mother’s blood.
Binds 2,3-BPG less avidly than HbA

Question 39

When does beta globin production exceed gamma globin production?

Answer 39

Between 1 and 6 weeks postnatal

Question 40

Sickle cell anaemia cause

Answer 40

Amino acid in position 6 of beta globulin changed from glutamate to valine.
Valine is hydrophobic, can stick to a hydrophobic pocket in deoxy Hb. This forms an insoluble crystalline structure.
Vaso-occlusion can result.