Hemoglobin- Structure and Function

Question 1

How many pairs of polypeptide chains are contained in a single hemoglobin?

Answer 1

2 Pairs

Question 2

What polypeptide chains make up Hemoglobin A1?

Answer 2

2 alpha chains and 2 beta chains

Question 3

What polypeptide chains make up Hemoglobin A2?

Answer 3

2 alpha chains and 2 delta chains

Question 4

What polypeptide chains make up Hemoglobin F?

Answer 4

2 alpha chains and 2 gamma chains

Question 5

True or False: A total lack of alpha-globin chains is compatible with life.

Answer 5

False. There is no substitute for alpha-chains so the a total lack of alpha chains is incompatible with life

Question 6

What three amino acids make the surface of hemoglobin hydrophilic (preventing it from precipitation)?

Answer 6

Lysine
Arginine
Glutamic Acid

Question 7

Define: Allosteric regulation.

Answer 7

Binding to substrate, oxygen, the hemoglobin molecule changes its conformation, altering the binding affinity for additional oxygen molecules.

Question 8

Describe: Configuration T (Taut) of hemoglobin

Answer 8

No sites are occupied by oxygen

Question 9

Descrbie: R form (relaxed) of hemoglobin

Answer 9

All sites are occupied by oxygen

Question 10

What is positive coopertivity?

Answer 10

Binding of a substrate leading to increased affinity for additional substrates

Question 11

What has a higher oxygen affinity myoglobin or hemoglobin?

Answer 11

Myoglobin

Question 12

What is the interpretation of a left shift on a dissociation curve?

Answer 12

Left shift means the hemoglobin has an increased oxygen affinity and a lower P50

Question 13

What is the interpretation of a right shit on a dissociation curve?

Answer 13

Decreased oxygen affinity and higher P50

Question 14

Name three factors that shift the oxygen dissociation curve.

Answer 14

1. pH
2. Temperature
3. 2,3-BPG concentration

Question 15

What is the Bohr Effect?

Answer 15

Oxygen held more tightly in higher pHs and released more easily in acidic environments

Question 16

How does carbon dioxide effect the dissociation of oxygen from hemoglobin?

Answer 16

Right shift.

Carbonic anhydrase converts carbon dioxide to carbonic acid which decomposes into bicarbonate and hydrogen ions leading to a drop in pH.

Question 17

How does higher temperature effect the dissociation curve?

Answer 17

Higher temperature shifts the curve to the right

Question 18

What is 2,3-Bisphosphoglycerate?

Answer 18

-It is a byproduct of anaerobic glycolytic pathway

Question 19

How does 2,3-BPG effect the dissociation curve?

Answer 19

High 2,3-BPG: Oxygen affinity of hemoglobin decreases and shifts to the right

Mechanism- Stabilizes deoxyhemoglobin in T configuration leading to decreased affinity

Question 20

Define P50.

Answer 20

The partial pressure of oxygen at which the oxygen carrying protein is 50% saturated

Question 21

Why is the oxygen dissociation curve sigmoidal in shape?

Answer 21

Because of COOPERATIVITY, when the percent saturation of hemoglobin by oxygen is plotted as a function of the partial pressure of oxygen

Question 22

Compare oxygen dissociation curves for myoglobin and hemoglobin and explain the reasons for the difference

Answer 22

Myoglobin- is a protein which stores oxygen in muscle cells and is very similar to hemoblobin except that it is a monomer rather than a tetramer and therefore does not undergo allosteric regulation or cooperativity.

The myoblobin curve is shaped more like a hyperbola, giving the myoglobin molecule very high oxygen affinity at very low oxygen concentrations

Question 23

On what chromosome is alpha globin found?

Answer 23

Chromosome 16

Question 24

On what chromosome is beta globin found?

Answer 24

Chromosome 11

Question 25

What three distinct hemoglobins are found in embryos between week 4 and week 14? What is a common characteristic of all three?

Answer 25

1. Hemoglobin Gower I 2. Hemoglobin Gower II 3. Hemoglobin Portland -They all have a higher affinity for oxygen (left shift) than adult hemoglobin

Question 26

What hemoglobin predominates after 8 weeks of gestation?

Answer 26

Fetal hemoglobin

Question 27

Name one unique feature of fetal hemoglobin.

Answer 27

It binds 2,3-BPG poorly giving it a higher oxygen affinity

Question 28

What hemoglobin predominates at eh time of birth?

Answer 28

65-95% Hemoglobin F | 20% Hemoglobin A1

Question 29

What two conditions results in hemoglobin F remaining elevated after birth?

Answer 29

Premature infants | Mom with diabetes

Question 30

Name some unique characteristics of Hemoglobin A2.

Answer 30

- More heat setable - Slightly higher oxygen affinity - Can become elevated in certain diseases

Question 31

What are Heinz bodies?

Answer 31

They are precipitated denatured hemoglobin. They are a result of variants producing a physically unstable molecule

Question 32

What is high affinity hemoglobin variants?

Answer 32

Hemoglobin variant that holds onto oxygen more tightly (left shift).

Question 33

What is a common symptom of people with high affinity hemoglobin variants?

Answer 33

Erythrocytosis due to oxygen delivery being reduced leading to erythropoietin being produced leading to increased red blood cell production.

Question 34

Give one example of a high affinity hemoglobin variant

Answer 34

Hemoglobin Chesapeak

Question 35

What is low affinity hemoglobin variants?

Answer 35

Hemoglobin releases oxygen too easily (right shift)

Question 36

What is a common symptom of people with low affinity hemoglobin variants?

Answer 36

Cyanosis and physiological anemia

Question 37

True or False: Hemoglobin Zurich is a low affinity hemoglobin variant.

Answer 37

False. The mutation does not affect oxygen binding but does increase binding to carbon monoxide

Question 38

What are some characteristics of Hemoglobin Koln?

Answer 38

- Most commonly recognized unstable Hgb - Mild Anemia - Reticulocytosis - Splenoomegaly

Question 39

What is methemoglobin?

Answer 39

It is hemoglobin with ferric (3+) instead of ferrous (2+)

Question 40

What maintains iron in the ferrous form of iron in the erythrocyte?

Answer 40

NADPH methemoglobin reductase pathway

Question 41

How can you get acquired methemoglobinemia?

Answer 41

Exposure to drugs such as benzocaine or nitrates in well water

Question 42

What causes genetic methemoglobinemia?

Answer 42

Homozygous deficiency of cytochrome b5 reductase which is responsible for the transfer of electrons from NADH to cytochrome b5 May also be mutation in hemoglobin that leads to methemoglobin

Question 43

What would an oxygen dissociation curve look like for someone with methemoglobinemia?

Answer 43

Left shift

Question 44

What are they symptoms of methemoglobinemia?

Answer 44

Cyanotic, but arterial partial pressure is normal Blood looks chocolate, brown-blue

Question 45

What is the treatment for patients with methemoglobinemia?

Answer 45

Cosmetic with methylene blue | Remove inciting drug for acquired

Question 46

What binds heme better CO or O2

Answer 46

CO2!!!! About 240X better

Question 47

A 15 yo boy comes into the ER. In the ambulance he had a seizure and then became unresponsive. His friend reported that an hour prior he was nauseated and dizzy. The friend seemed disoriented and disconnected and was shielding his eyes from the bright light of the emergency room. What should be on the differential diagnosis?

Answer 47

Carbon monoxide poisoning. possibly from sniffing pain remover

Question 48

What is the treatment for carbon monoxide poisoning?

Answer 48

100% oxygen to competitively compete

Question 49

Can you diagnose carbon monoxide poisoning with pulse oximetry?

Answer 49

No. Pulse oximetry only measures two wavelengths and cannot differentiate between carboxyhemoglobin and oxyhemoglobin. Co-oximetry measures four wavelengths and can accurately measures carboxyhemoglobin and methemoglobin