Term 1- Lec 4- Hb & Mb

Question 1

Myoglobin location and basic function

Answer 1

Heart and skeletal muscle, and small amounts of smooth muscle. Stores O2.

Question 2

Hemoglobin location and basic function

Answer 2

Erythrocytes. Delivers O2 from the lungs to tissues and CO2 from the tissues to the lungs.

Question 3

Which Iron cation is bound to the heme group in hemoglobin

Answer 3

Fe2+ (Ferrous iron). Methemoglobin–bound to Fe3+ (Ferric iron) does not bind O2.

Question 4

What binds to the 5th coordination site of Heme?

Answer 4

Proximal histidine

Question 5

What stabilizes O2 when it’s bound to the 6th coordination site of Heme?

Answer 5

Distal histidine

Question 6

Why is the Heme group necessary, and not just Fe2+?

Answer 6

Binding only ionic iron is irreversible and would not function in O2 delivery

Question 7

When does Myoglobin release it’s O2?

Answer 7

At very low O2 concentrations, only in the tissues. Hyperbolic dissociation curve

Question 8

Mb and Hb O2 affinities in:1) Lungs, 2) Tissues

Answer 8

They both have similar, high affinity for O2 at lung concentrations. They differ in tissues, Mb keeps most of it’s O2 in normal tissue concentrations, doesn’t release until the tissues are below their normal O2 levels. Hb unloads it’s O2 in the normal tissue concentration

Question 9

T state

Answer 9

Lowered affinity for O2, takes this shape when unbound to O2 (most often in tissues). Named deoxyhemoglobin

Question 10

R state

Answer 10

Significantly higher affinity for O2, takes this state when in the lungs. Named oxyhemoglobin

Question 11

How does binding O2 change the conformation of Hemoglobin?

Answer 11

3º structure changes thus 4º structure changes too. O2 Pulls Fe into plane of porphyrin ring, Fe pulls proximal His forward, F helix moves as well do to steric repulsion.

Question 12

Cooperativity in Hemoglobin

Answer 12

O2 binds to one subunit, stabilizing it in that state AND pressuring the other subunits to adopt the shape thus raising it’s affinity toward O2.

Question 13

Allosteric regulation requires

Answer 13

4º structure (at least 2 proteins)

Question 14

Homotropic

Answer 14

The effector ligand is identical/very similar to the true ligand

Question 15

Heterotropic

Answer 15

The effector ligand is different from the true ligand

Question 16

Negative effectors

Answer 16

Inhibitors- decrease protein activity. Shift binding curves to the right. Decreased affinity allows for more O2 to be released in the tissues.

Question 17

Poitive effectors

Answer 17

Activators- Increase protein activity. Shift the binding curve to the left

Question 18

The ligands for Hemeglobins

Answer 18

2,3-BPG, CO2, H+ (Bohr’s effect)- negative effectors. CO- positive effector (but bad).

Question 19

2,3-BPG affect on Hb

Answer 19

2,3-BPG is a negative allosteric effector of Hb. It stabilizes the T state by binding through inoic bonds in the central cavity “holding it open”. Only fits in center when Hb is in T state. Promotes release of O2.

Question 20

Fetal Hb has higher affinity to O2 than Adult Hb because:

Answer 20

HbF cannot bind 2,3-BPG, thus, without the negative effector, it has higher affinity

Question 21

CO2 affect on Hb

Answer 21

CO2 is a negative allosteric effector of Hb. It binds N-terminus of Hb via an ionic bond (negatively charged now) stabilizing.

Question 22

In what form does CO2 get to the lungs?

Answer 22

20% of exhaled CO2 is transported as CO2 bound to the N-terminus of Hb. Most (75%) CO2 is transported as bicarbonate (HCO3-)

Question 23

What does a graph look like of Hb with negative effectors bound to it?

Answer 23

The sigmoidal curves shift right. CO2 the least, 2,3-BPG more than CO2, the two combined make the furthest curve.

Question 24

H+ effect on Hb-Bohr Effect (in tissues)

Answer 24

H+ is a negative allosteric effector. It binds at a His of the ß-subunit, changing the protonation state. Increased [H+] = increased O2 delivery.

Question 25

H+ effect on Hb-Bohr Effect (in lungs)

Answer 25

H+ increase the amount of CO2 exhaled. [O2] is so high that O2 automatically saturates Hb. Binding O2 releases H+ —> HCO3- + H+ —> H2CO3 —> H2O + CO2 (via CARBONIC ANHYDRASE)—> CO2 is exhaled.

Question 26

Hb affinity to CO

Answer 26

Much, much higher than it’s affinity to O2

Question 27

CO effects of binding to Hb

Answer 27

Binds to same site as O2 and increases affinity for O2, but locks the Hb in the R state and does not release the O2 in the tissues- acts as storage. CO shifts the saturation curve LEFT.