Biochemistry

Question 1

Describe the important residues in Hb

Answer 1

His F8 - anchors haem

E7 - prevents H2O binding in deoxy state to prevent transformation to Met Hb

Question 2

What is Met Hb?

Answer 2

Hb with oxidised haem (Fe3+)

Dark brown in colour

Question 3

Describe the different conformation states of Hb

Answer 3

Relaxed (R) = (r)oxy

Tense (T) = (T,de)oxy

Question 4

How does Hb switch between T and R states?

Answer 4

Binding of O2 to one subunit alters plane of Fe2+ in porphyrin ring
H-bonds form between a and B subunits

Question 5

What is the role of 2,3-BPG in Hb?

Answer 5

2,3-BPG is produced by tissues and RBCs, and binds allosterically to Hb to stabilise the deoxy (T) state, encouraging O2 offloading
Its binding site is closed by O2 binding at the lungs

Question 6

What is the Bohr effect?

Answer 6

H+ stabilies deoxy-Hb (encourages O2 offloading)

Question 7

What effect does CO2 have on Hb?

Answer 7

Pulls O2 saturation curve to the right (allosteric modulator that stabilises deoxy-Hb)

Question 8

What changes occur at high altitudes to maintain O2 delivery to tissues?

Answer 8

Increased 2,3-BPG in RBCs

EPO release from kidneys to increase RBC production

Question 9

How does HbF bind O2 with more affinity than HbA?

Answer 9

Less affinity for 2,3-BPG due to a single AA change

Question 10

What is the causative mutation in sickle cell anaemia?

Answer 10

Point mutation leads to substitution of glutamate with valine (a hydrophobic residue; creates a “sticky spot” leading to RBC aggregation)

Question 11

Why is the O2 association curve sigmoid?

Answer 11

Hb has allosteric cooperation