Haemoglobin

Question 1

Red blood cell function

Answer 1

• transfer O2 from lungs to tissue

- transfer CO2 from tissue to lungs

Question 2

Where is myoglobin found?

Answer 2

skeletal and heart muscle

Question 3

Myoglobin function

Answer 3

• facilitates rapidly respiring muscle tissue
• increases oxygen solubility
• facilitates oxygen diffusion

Question 4

Myoglobin structure

Answer 4

• haem with 2 His residues

Question 5

Histidine

Answer 5

• imidazole side chain
• pKa = 6
• protonated below pH6
• common in catalytic sites & metalloproteins

Question 6

Globin gene family

Answer 6

• encode haemoglobin
• different globin genes expressed during development which alter oxygen affinity of embryonic and foetal Hb
• globins synthesised in polyribosomes

Question 7

Where are haem groups systhesised?

Answer 7

mitochondria

Question 8

Haemoglobin structure

Answer 8

• tetramer with 2 alpha and 2 beta subunits

- each subunit has a Haem

Question 9

Haem

Answer 9

• centralised Fe atom
• carries oxygen
  heterocyclic porphyrin derivative - protoporphyrin IX

Question 10

Fe in haemoglobin

Answer 10

must be Fe(II) to bind oxygen

Question 11

Methemoglobin

Answer 11

• Hb with Fe(III) -can’t bind oxygen
• usually 1-2% of Hb; over that it becomes dangerous
• increase can be caused by benzocaine, nitrites, arsine

Question 12

deoxyHb structure

Answer 12

domed

Question 13

oxyHb

Answer 13

planar

Question 14

BPG (DPG)

Answer 14

• modulates Hb affinity for oxygen
• provides control and potential for adaptation (eg altitude)
• allosteric effector

Question 15

Hb cooperativity

Answer 15

positive - sigmoidal curve

Question 16

Hb-oxygen dissociation curve depends on:

Answer 16

[BPG] - only has effect on oxygen release and not binding
pH
Hb structure
CO2 in red blood cells

Question 17

Hb-O2 curve shift to left

Answer 17

oxygen given up less readily

• low BPG
• HbF

Question 18

Hb-O2 curve shift to right

Answer 18

easy oxygen delivery

• high BPG
• high [H]
• high [CO2]
• HbS

Question 19

Picket fence Fe(II)-porphyrin complex with bound oxygen

Answer 19

• O2 binds to 6th ligand of Fe(II) out of haem plane
• 5th ligand is a His, F8 on side across the haem plane
• His F8 binds to proximal side
• Oxygen binds to distal side

Question 20

oxy vs deoxy Hb

Answer 20

major structural differences between quaternary conformations
T –> R shift

Question 21

O2 changes electronic state

Answer 21

Fe moves into plane dragging proximal His, which tilts and drags F helix

Question 22

when can proximal His move?

Answer 22

when movement is accompanied by F helix translation across haem plane

Question 23

When does F helix translation occur

Answer 23

with quaternarT - y shift that steps he a1C-b2FG contact one turn along the a1C helix.

Question 24

bonds in Hb

Answer 24

H-bonds, salt bridges

Question 25

Bohr effect

Answer 25

pH shift - higher pH promotes tighter O2 binding - lower pH permits easier release of O2 from Hb

Question 26

pO2 in lungs vs capillaries

Answer 26

lungs - high | capillaries - low

Question 27

Cl- effect

Answer 27

Hb affinity for O2

Question 28

T - state Hb

Answer 28

stabilised by H-bonds

Question 29

Sickle cell anaemia

Answer 29

genetic disease glu6 --> val aggregation of Hb low O2 supply to tissues pain, organ damage, stroke, increased