Hemoglobin

Question 1

what is an allosteric inhibitor?

Answer 1

binds away from the active site but inhibits binding of the substrate at the active site

Question 2

How and to what does BPG bind?

Answer 2

BPG binds to deoxy-Hb by electrostatic interactions.

Question 3

what state does BPG stabilise?

Answer 3

BPG stabilises Hb in the deoxy T-state, reducing oxygen affinity.

Question 4

When and why is BPG produced?

Answer 4

BPG is produced during respiration in peripheral tissues, so promotes oxygen release where it is needed

Question 5

What happens during exercise that changes O2 binding affinity?

Answer 5

More CO2-> blood more acidic -> reduced sigmoidal curve ->
• CO2 binds at terminal amino group (close to BPG binding site) and
• Decreased pH = more H+ -> protonation of histidine’s of BPG binding site
-> binds BPG better -> helps stabilize t-state -> decreased affinity for O2

Question 6

What is the body’s short term response to increased altitude

Answer 6

increased BPG production = O2 held on less tightly = increased ability to dump it in the tissues

Question 7

What is the body’s long term response to increased altitude

Answer 7

LT: make more hemoglobin so greater capacity overall

Question 8

What is different about fetal hemoglobin that allows them to outcompete their mother for O2?

Answer 8

Fetal hemoglobin includes alternate isoforms (different aa sequences) with higher affinity for O2 - i.e. gamma subunit

Question 9

How does the gamma subunit work?

Answer 9

Gamma subunit is worse at binding BPG .: better at binding O2, able to suck it across the placenta more easily

Question 10

What chemical change does the gamma subunit feature?

Answer 10

Serine instead of histidine on BPG binding site
-> Neutral hydroxyl side chain instead of positive histidine = decreased BPG binding

Question 11

What is methemoglobin?

Answer 11

Oxidation of heme from Fe2+ to Fe3+ -> shifts one subunit to R state without O2 binding

Question 12

What is the effect of methemoglobin?

Answer 12

When Fe2+ goes to Fe3+ and one subunit shifts to R state without O2 binding, other subunits are shifted to R state so do not release the O2 into the tissue that they should

Question 13

What is Boston hemoglobin?

Answer 13

E7 mutation causes Fe2+ to oxidize to Fe3+
- Remains in t state -> low affinity for O2

Question 14

What is sickle cell hemoglobin? What mutation causes it?

Answer 14

• E6V mutation = abnormal hydrophobic interaction between Hb molecules
• Causes polymerization of Hb into chains that distort RBCs