Hemoglobin/Myoglobin

Question 1

What are hemeproteins

Answer 1

Proteins that contain heme as a tightly bound prosthetic group

Question 2

What is a prosthetic group

Answer 2

Coenzyme that is permanently attached to an enzyme or protein that stays bound and gets recycled to be reused

Question 3

Name 4 heme proteins

Answer 3

Cytochromes, catalase, myoglobin and hemoglobin

Question 4

Function of myoglobin

Function of hemoglobin

Answer 4

Used to reversibly bind oxygen - not in the blood stream, its in muscle

Used to reversibly bind oxygen in the blood stream

Question 5

Structure of heme

Heme can make two additional bonds between what two things?

Answer 5

Fe2+ in middle by bonds of 4 nitrogens of the porphyrin ring

R group of a histidine and oxygen

Question 6

Presence of oxygen on heme plays an important role for

Answer 6

Relaxed/taut state

Question 7

Myoglobin

1. Located
2. 2 functions
3. Myoglobin is a single polypeptide similar to

Answer 7

1. In skeletal muscle and heart
2. Oxygen reservoir, oxygen carrier that increases rate of transport within muscle cell
3. Individual alpha and beta globin chains found in hemoglobin

Question 8

Myoglobin:

1. 80% of it is
2. Heme group is lined with?
3. Function of the two histidines
4. What moves faster in the cell: oxygen or myoglobin

Answer 8

1. Alpha helix structures
2. Nonpolar amino acids except for 2 histidine residues
3. One binds to iron of heme; other stabilizes the binding of oxygen to the iron
4. Myoglobin; so it helps with the transfer of oxygen- also because it has high affinity

Question 9

Myoglobin has similar structure of hemoglobin except

Answer 9

Hemoglobin is myoglobin x4

~myoglobin is monomer; hemoglobin is tetramer

Question 10

Hemoglobin:

1. Found where
2. Major goal
3. Structure

Answer 10

1. RBCs
2. Deliver oxygen from the lungs to the tissue
3. 2 alpha chains and 2 beta chains. Alpha and beta chains are hooked together via hydrophobic interactions (alpha beta dimer associated with another alpha beta dimer)

Question 11

Hemoglobin

1. How many oxygens can hemoglobin transport
2. What else besides oxygen can hgb transport

Answer 11

1. 4 (from lungs to tissue)

2. CO2 and H+ from peripheral tissues back to lungs

Question 12

Hemoglobin:
So alpha beta dimer and alpha beta dimer are held together by hydrophobic interactions; how are the two dimers held together

Answer 12

Weaker ionic and hydrogen bonds (amount of polar bonding between the two dimers depends on whether or not oxygen is bound)

Question 13

1. Taut form of hgb has more

2. Relaxed form has more

Answer 13

1. Ionic and hydrogen bonds and fewer oxygens are bound (which means less affinity for oxygen)
2. Oxygen is bound which causes conformation to bury some charges/R group chains that have hydrogen bonding capability

Question 14

What drives the relaxation of the bonds between the dimers?

Answer 14

When one O2 binds it changes the conformation, relaxes the bonds and causes the structural change in the rest of the tetramers that holds the alpha helices together and increases the affinity for more O2

Question 15

Affinity of oxygen is defined by?

Answer 15

P50; 50% of oxygen saturation

Question 16

How do you move on the graph to represent unloading of oxygen from the heme molecule

Answer 16

Moving down the graph and to the left

Question 17

As the graph shifts to the right, what is happening to oxygen affinity?

So as p50 goes up (pO2 on x axis), oxygen affinity goes down…why?

Answer 17

Oxygen affinity is going down

Shift to the right means you have to have more oxygen in the environment to have 50% of molecule loaded
Vice versa for left shift

Question 18

Which has a higher affinity for oxygen: myoglobin or hemoglobin

Answer 18

Myoglobin (so it is more left on the graph)

Question 19

Is it more common to see a right sided shift or left sided shift

Answer 19

Right sided shift (shifting towards less affinity for oxygen)

Question 20

Hemoglobin curve

1. Y axis is
2. X axis is

Answer 20

1. Degree of saturation

2. Partial pressure of oxygen where a low p50=high affinity and a high p50=low affinity

Question 21

If you do not have a high demand for oxygen, then oxygen content in the blood stream at the capillary bed will be high or low?

Answer 21

High - less offloading because you don’t need that much in the tissues

~when exercising, it will be low because your tissues have a higher demand for O2

Question 22

Shape of myoglobin on the graph

Shape of hemoglobin

Answer 22

Hyperbolic

Sigmoidal

Question 23

Myoglobin is designed to do what

Answer 23

Bind oxygen at low pO2 found in muscle (releases oxygen in response to oxygen demand)

Question 24

Explain the heme-heme interaction

Answer 24

If you bind one oxygen, it increases the affinity for oxygen of the remaining heme groups in the same hgb molecule

Question 25

Name 3 allosteric effectors of heme-heme interaction

Answer 25

(PO2), pH, pCO2, and 2,3-BPG

Question 26

In peripheral tissues, lower pO2 will allow

Answer 26

Oxygen unloading

Question 27

Hemoglobin has less affinity for oxygen at what pH (Bohr effect) Which way will this shift the curve

Answer 27

Lower pH To the right

Question 28

Hemoglobin delivers oxygen from site of __ pO2 to __ pO2 When will myoglobin release oxygen?

Answer 28

High to low At close to zero pO2

Question 29

Bohr effect PH is higher in lungs and lower in peripheral tissues; what does this do to the efficiency of hgb as an oxygen transporter

Answer 29

Increases its ability as an oxygen transporter

Question 30

Bohr effect Which has a higher affinity for protons: deoxyhemoglobin or oxyhemoglobin 3 features of protonated version

Answer 30

Deoxy Stroner ionic interactions, more stable taut form and lower affinity for oxygen

Question 31

2,3 BPG 1. Binds to? 2. Stabilizes what form 3. What does it do to affinity of hgb for oxygen 4. Where is the binding site for 2,3 BPG

Answer 31

1. Only to deoxyhemoglobin 2. Taut form 3. Decreases 4. In between 2 beta globin chains in deoxyhemoglobin

Question 32

If you had no 2,3 BPG how would curve shift

Answer 32

To the left (such that it binds oxygen with such high affinity)

Question 33

What happens to 2,3 BPG levels with chronic hypoxia / high altitude / anemic patients

Answer 33

2,3 BPG levels increase

Question 34

How is most CO2 transported Some CO2 is transported as __; this binding stabilizes what form and results in graph shifting to the

Answer 34

In form of bicarbonate ion Carbamate that forms carbaminohemoglobin; T form; right

Question 35

CO (carbon monoxide) 1. How does it bind to HgB 2. Binding supports which form 3. Shifts curve to the 4. So high O2 affinity and oxygen binding sites occupied by CO results in?

Answer 35

1. Tightly (hgb has high affinity for CO) 2. Relaxed 3. Left 4. Critically low oxygen unloading at peripheral tissues

Question 36

Fetal hemoglobin (HbF) 1. Structure 2. __ affinity for 2,3 BPG, why? 3. __ affinity for oxygen

Answer 36

1. 2 alpha chains and 2 gamma chains 2. Low - gamma chains lack some postive AAs that the 2,3 BPG interacts with 3. High (able to absorb oxygen from maternal circulation

Question 37

How is HbA1C formed?

Answer 37

By glycolation of HbA - so if you have a lot of sugar in your blood, you will have a high HbA1C

Question 38

Sickle cell anemia: 1. When are symptoms shown 2. Symptoms 3. Lifetime of these RBCs 4. Need to avoid what two things 5. Mutation that causes this 6. Treatment

Answer 38

1. ~6 months of age, when HbF is replaced by HbS 2. Pain, hemolytic anemia, increased susceptibility of infection 3. Less than 20 days (normal RBC is 120 days) 4. Dehydration and extreme exercise 5. Glutamate replaced by valine (less negatively charged) 6. Hydroxyurea (antitumor drug) - can increase amount of HbF which decreases sickling

Question 39

Hemoglobin C disease 1. Caused by 2. Leads to

Answer 39

1. Lysine substituted for glutamate | 2. Mild chronic hemolytic anemia, no crises, no specific therapy required

Question 40

Hemoglobin SC disease: 1. Caused when 2. Symptoms

Answer 40

1. When a patient inherits one copy of HbS and one copy of HbC 2. Variable; between more severe sickle cell anemia and less severe hemoglobin C disease