Cooperativity and Allostery in haemoglobin and oxygen transport

Question 1

haemoglobin vs myoglobin?

Answer 1

myglobin

• monomer
• binds one O2 with michaelis-menten-like kinetics
• located in muscles, provides a reserved supply of oxygen

haemoglobin

• tetramer
• binds 4 O2 molecules with cooperative kinetics
• binding affinity is allosterically regulated

Question 2

describe the structure of the adult form of haemoglobin

Answer 2

• 4 globin subunits
• 2 alpha chains
• 2 beta chains
• heterotetramer

Question 3

what is the purpose of distal histidine

Answer 3

purpose is to prevent the oxygen binding too tightly to the ferrous atom on the heme group

distal histidine prevents oxidation, otherwise the ferric form of the iron would be unable to bind oxygen, this would also lead to superoxide release

Question 4

what is the difference between the r state and the t state

Answer 4

relaxed state- tightly binds S
relaxed state is the oxygenated form of Hb

tense state - weakly binds S
deoxygenated form = tense state

Question 5

what is the role of 2,3-bisphosphoglycerate

Answer 5

• is an allosteric inhibitor of haemoglobin
• binds in the central cavity of deoxyhaemoglobin
• stabilises the T state
• reduces affinity for O2
• released only under high levels of O2

binding of 2,3-BPG lowers the affinity of haemoglobin. without this, little oxygen could be delivered to tissues

Question 6

describe some of the key features of the oxygen binding site

Answer 6

heme group contains a ferrous atom

• oxygen binds to the ferrous atom
• Fe2+ requires 6 coordination bonds, 4 are provided by the porphyrin nitrogen atoms, 5th by His F8 and 6th is the O2 coordination bond