Structure & Function of Hb/Mb

Question 1

Where does Hb bind and release O2, respectively?

Answer 1

Lungs (alveoli) & Tissues

Question 2

Where does external respiration (exchange of gas with external environment) occur?

Answer 2

alveoli of the lungs

Question 3

Where does internal respiration (exchange of gas with internal environment) occur?

Answer 3

Tissues

Question 4

What drives the exchange of gases (O2 & CO2) across the membranes?

Answer 4

Partial pressure (pressure gradient)

Question 5

Characteristics of Myoglobin

Answer 5

tertiary structure of a single polypeptide chain; most are in alpha-helical shape; 1 O2 at heme; O2 storage in tissues;

NOT allosteric (only those with quaternary structure can be allosteric)

Question 6

Characteristics of Hemoglobin

Answer 6

Tetramer of 4 polypeptide chains (2 alpha & 2 beta chains); 4 O2 per Hb; O2 transport from lungs to tissues; CO2 from tissues to lungs; allosteric protein (since it has quaternary structure)

Question 7

HbA is composed of

Answer 7

a2B2

most abundant (98%) type of normal Hb in adults

Question 8

HbA2 is composed of

Answer 8

a2D2

rest type (2%) of normal Hb in adults

Question 9

HbF is composed of

Answer 9

a2Y2

major Hb in fetus until birth

Question 10

HbE is composed of

Answer 10

S2E2 or a2E2 or S2Y2

Embryonic Hb until birth

Question 11

What is the disorder caused by mutations in gene that is responsible for globin chain synthesis?

Answer 11

Thalassemia

Question 12

Structure of Heme

Answer 12

Fe-protoporphyrin IX

1. one Fe2+ molecule is covalently bonded to 4 pyrrole rings.
2. hydrophobic chains formed by the pyrrole rings stabilize heme binding.

Question 13

What gives heme its red pigment?

Answer 13

porphyrin rings

Question 14

what other colors are given by porphyrin rings?

Answer 14

chlorophyll (green)

cyanocobalamin or B 12 (pink)

Question 15

What is the disorder caused by mutations in the heme biosynthesis pathway?

Answer 15

porphyria

Question 16

Binding curve of Mb

Answer 16

Hyperbolic; binds O2 tightly at all times; only releases O2 when under stress conditions

Question 17

Binding Curve for Hb

Answer 17

Sigmoidal; lower affinity for O2 than Mb; releases 50% of O2 in tissues

Question 18

T state of Hb

Answer 18

Tense; in tissues; low O2 affinity; Deoxyhemoglobin

Question 19

R state of Hb

Answer 19

Relaxed; lungs (R=respiratory); high O2 affinity; Oxyhemoglobin; binding of O2 stabilizes R state due to positive cooperativity

Question 20

T/F: O2 is a positive allosteric regulator of Hb O2 binding because O2 causes a conformational change at each aB dimer interface in the Hb molecule.

Answer 20

True

Question 21

Negative Allosteric Inhibitors

Answer 21

Stabilize T state; negative effect on O2 binding=release of O2; shifts curve to right; 2,3-BPG, CO2, H+ (decrease pH-Bohr Effect)

Question 22

2,3- BPG

Answer 22

Negative Inhibitor; binds central cavity and holds Hb in T state

Question 23

What are situations in which 2,3-DPG levels are increased?

Answer 23

1. COPD
2. Pregnancy
3. High altitude
4. Chronic Anemia

Question 24

CO2

Answer 24

Negative Inhibitor; binds N-terminus creating a negative charge, allowing ionic binds to stabilize the T State

Question 25

Haldane Effect

Answer 25

The Haldane effect describes how oxygen concentrations determine hemoglobin’s affinity for carbon dioxide.

For example, high oxygen concentrations enhance the unloading of carbon dioxide.

Question 26

Bohr Effect

Answer 26

The Bohr effect describes how carbon dioxide and H+ affect the affinity of hemoglobin for oxygen.

High CO2 and H+ concentrations cause decreases in affinity for oxygen, while low concentrations cause high affinity for oxygen.

Question 27

What reaction is carried out by Carbonic Anhydrase?

Answer 27

1. CO2 + H2O –> H2CO3

2. H2CO3 –> CO2 + H2O

Question 28

H+

Answer 28

Negative Inhibitor; Decreases pH; Bohr Effect: high H+ in cells causing release of O2; low H+ in lungs allowing binding of O2

Question 29

Differences of Hb A and Hb F

Answer 29

1. Hb F has Y chain instead of B chain
2. Hb F > Hb A for oxygen affinity
3. Hb F binds 2,3-DPG poorly

Oxygen released by maternal Hb A is bound by Hb F and transported to fetal tissues.

Question 30

The most common Hb variant (mutation) associated with pathology in the U.S. is

Answer 30

Bs variant

• Bs mutation can lead to increased production of Hb S which is responsible for sickle cell disease.

Question 31

What are substances that compete with oxygen for binding at heme and inhibit oxygen binding?

Answer 31

CN- (cyanide); CO (carbon monoxide); NO2 (nitrogen dioxide); H2S (hydrogen sulfide)

They don’t change Iron oxidation state

Question 32

Carboxyhemoglobin

Answer 32

Complex formed of CO and heme that is readily formed and more stable than oxyhemoglobin (HbO2).

Elevated level of carboxyhemoglobin can lead to CO poisoning

Question 33

What is the disorder caused by mutations in any of 3 AAs on the distal side of heme?

Answer 33

Methemoglobinemia

Due to oxidation of Fe2+ to Fe3+ and is characterized by cyanosis (brown color of blood)

Question 34

What are other causes of methemoglobinemia?

Answer 34

1. Decrease in glutathione caused by mutations in the PPP causing G-6-PD deficiency.
2. Mutations in cytochrome b5 reductase causing inability of Fe3+ reduction to Fe2+ in methemoglobin.