UNIT TWO Hemoglobin + Affinity

2,3-BPG (2,3 biphospoglycerate)

negative heterotrophic stabilizing Hb to T-state, favoring release of O2

Binding site of 2,3-BPG

HB’s central cavity in (+) areas in residue; only binds to deoxyhemoglobin

components of fetal Hb

2 alpha units, 2 gamma units

What is the major amino acid change in Hb?

His143 —> Ser143

What does Ser143 do for Hb

increases affinity to 02, prevents BPG binding due to lack of (+) charge

What happens to BPG in low 02 environments?

BPG concentration increases with less 02 binding

NO and Cl- is a

negative heterotrophic effector

HCN is a

negative homotrophic effectors

CO2

negative heterotrophic effector forming carbamates from Hb amino group binding at N-terminal

Where does carbonic acid bind and what does it do

N-terminal, creates (-) charge for salt bridges —> 02 release

Hypocapnia

when CO2 levels decrease, favoring R state, no O2 release

positive cooperativity

first O2 binding increases affinity at remaining sites (sigmodial binding curve)

negative cooperatively

first binding decreases O2 affinity at remaining sites

If (Hill Coeff) n = 1, there is

no cooperativity

If (Hill Coeff) n < 1 , there is

negative cooperativity

If (Hill Coeff) n > 1, there is

positive cooperativity

Concerted Model

shows that there is always equilibrium between T/R states, as it moves to R-state (one change —> all change)

What is the limit of concerted model?

T state Hb without ‘O’ doesn’t exist

Sequential Model

shows how subunits shift from T to R without an intermediate

What mutation is involved with sickled cell

Glu 6 —> Val 6

What are other missense mutations in Hb?

His —> Try

Arg —> His

His —> Asp

Hemoglobin nH

3

Myoglobin nH

1