L3: Hemoglobin/Myoglobin Structure and Function

Question 1

What are hemoglobin and myoglobin?

Answer 1

Specialized globular hemeproteins that require heme as a tightly bound prosthetic group for O2 binding capacity.

Question 2

What is heme?

Answer 2

An organic cofactor comprised of Ferrous iron (Fe2+) associated with a heterocyclic porphyrin ring.

Question 3

What is the primary function of hemoglobin?

Answer 3

Required for cooperative binding of O2 and transports O2 to oxidatively active tissues to fuel metabolism.

Question 4

What is the primary function of myoglobin?

Answer 4

Serves as a storage reservoir for O2 in resting muscle and releases it upon contraction to replenish O2 supply.

Question 5

What are the structural characteristics of myoglobin and hemoglobin?

Answer 5

Share a characteristic tertiary structure (globin fold) mostly comprised of 8 α-helices disrupted by proline residues or β-bends and loops.

Question 6

What stabilizes the structure of myoglobin and hemoglobin?

Answer 6

Hydrophobic interactions between tightly packed nonpolar amino acids in the interior of the molecule.

Question 7

Which residues are involved in heme binding in hemoglobin?

Answer 7

Two histidine residues (F8 for heme binding; E7 for stabilization of O2 binding).

Question 8

Why is hemoglobin water soluble?

Answer 8

Due to charged amino acids at the surface that form hydrogen bonds with each other and water.

Question 9

What is the structural difference between hemoglobin and myoglobin?

Answer 9

Hemoglobin is a tetramer with two types of subunits; myoglobin is a monomer.

Question 10

What type of structure does hemoglobin have?

Answer 10

Quaternary structure composed of two identical α,β-dimers

The α,β-dimers are formed through strong hydrophobic interactions

Question 11

What interactions hold the two dimers of hemoglobin together?

Answer 11

Weak ionic and hydrogen bonds

These interactions help maintain the overall structure of hemoglobin

Question 12

What happens to the conformation of hemoglobin upon binding to O2?

Answer 12

It is altered

Each globin subunit binds Fe2+ iron in heme, which triggers the conformational change

Question 13

What is the effect of decreasing O2 availability on hemoglobin binding?

Answer 13

Decreased O2-binding affinity

Hb subunits do not bind O2 with high affinity in low O2 conditions

Question 14

What is the T state of hemoglobin?

Answer 14

Taut state with decreased O2-binding affinity

This state corresponds to deoxyhemoglobin

Question 15

What occurs when O2 availability is high for hemoglobin?

Answer 15

O2 binds to Hb subunit Fe2+, causing a conformational change

The polypeptide chain wraps less tightly, allowing easier O2 binding

Question 16

What is the R state of hemoglobin?

Answer 16

Relaxed state with increased O2-binding affinity

This state corresponds to oxyhemoglobin

Question 17

What is cooperative binding in hemoglobin?

Answer 17

When O2 binds to the first Hb subunit, its affinity for O2 increases

This initiates cooperation between other globin subunits for enhanced binding

Question 18

What occurs during cooperative binding of O2 to hemoglobin?

Answer 18

Each successive O2 molecule binds more rapidly with increasing affinity

Some ionic and hydrogen bonds between the α,β-dimers are broken

Question 19

What type of protein is hemoglobin?

Answer 19

Allosteric protein

An allosteric protein has multiple ligand-binding sites, and ligand binding at one site affects binding at another site.

Question 20

What is the effect of O2 on hemoglobin?

Answer 20

Positive homotropic effector

Question 21

What are the two states of hemoglobin based on O2 binding?

Answer 21

Deoxyhemoglobin (T state) and oxyhemoglobin (R state)

Question 22

How many O2 molecules can a hemoglobin molecule bind?

Answer 22

Zero or four

Question 23

What is the significance of hemoglobin’s allosteric properties?

Answer 23

Allows O2 binding in lungs and O2 release in other tissues

Question 24

What type of curve does myoglobin exhibit in relation to O2 affinity?

Answer 24

Hyperbolic curve

Question 25

Why does myoglobin have a higher affinity for O2 than hemoglobin?

Answer 25

To allow transfer of O2 from Hb to Mb in muscle for storage

Question 26

What condition leads to myoglobin being saturated with O2?

Answer 26

Resting muscle

Question 27

What happens to O2 levels during muscle contraction?

Answer 27

O2 is consumed by mitochondria, depleting O2 levels

Question 28

What role does myoglobin play during muscle contraction?

Answer 28

Releases O2 to replenish O2 supplies

Question 29

What type of curve does hemoglobin exhibit, and what does it demonstrate?

Answer 29

Sigmoidal curve; demonstrates allosteric nature and cooperative binding

Question 30

Where is O2 released by hemoglobin after binding in the lungs?

Answer 30

Oxidatively active tissues

Question 31

What is the P50 value?

Answer 31

Partial pressure of O2 at which a molecule is 50% saturated with O2

Question 32

What is the relationship between O2 affinity and P50 value?

Answer 32

Higher O2 affinity results in a lower P50

Question 33

What effect does high O2 binding have on hemoglobin conformation?

Answer 33

Fosters conversion from T to R conformation ## Footnote This occurs in the lungs.

Question 34

What promotes the conversion of hemoglobin from R to T conformation?

Answer 34

Low O2 levels in tissues and other variables ## Footnote This facilitates O2 release in tissues that require it.

Question 35

What are the two major metabolic pathways that modulate O2 binding and release by hemoglobin?

Answer 35

* Citric acid cycle * Glycolytic pathway ## Footnote They act as negative allosteric effectors.

Question 36

What does the citric acid cycle produce that affects hemoglobin?

Answer 36

CO2 ## Footnote CO2 is formed upon oxidative metabolism of food.

Question 37

What intermediate product does glycolysis produce in RBCs?

Answer 37

2,3-bisphosphoglycerate (2,3-BPG) ## Footnote It is present at constant levels in RBCs under normal conditions.

Question 38

What is the role of CO2 in the cellular environment?

Answer 38

Acts as a negative heterotropic effector ## Footnote It influences pH changes.

Question 39

How does CO2 affect pH in the blood?

Answer 39

Forms an acid that decreases pH ## Footnote CO2 dissolves in water, forming H+ ions.

Question 40

What is the primary form in which CO2 is carried in the blood?

Answer 40

Bicarbonate ion (HCO3-) ## Footnote Most CO2 is carried this way.

Question 41

How does lower pH affect O2 binding to hemoglobin?

Answer 41

O2 binds to Hb with lower affinity ## Footnote This occurs at lower pH levels.

Question 42

What is produced in the lungs due to the reversal of the bicarbonate reaction?

Answer 42

CO2 and water ## Footnote CO2 is exhaled as a byproduct of this reaction.

Question 43

What role does bicarbonate ion play in the blood?

Answer 43

Buffers H+s to increase pH ## Footnote This helps to regulate the acidity of the blood.

Question 44

How does higher pH affect O2 binding to hemoglobin (Hb)?

Answer 44

Increases affinity of O2 for Hb ## Footnote At higher pH, O2 binds more readily to hemoglobin.

Question 45

What is the Bohr effect?

Answer 45

Influence of pH and pCO2 on O2 binding affinity of Hb ## Footnote It describes how changes in pH and pCO2 affect oxygen release and binding.

Question 46

What is the relationship between deoxyHb and protons?

Answer 46

DeoxyHb has a greater affinity for protons than oxyHb ## Footnote This promotes O2 release in tissues with lower pH.

Question 47

Where is CO2 directly bound in hemoglobin?

Answer 47

To the N-terminal α-amino group of Hb subunits ## Footnote This forms carbaminohemoglobin.

Question 48

What is formed when CO2 binds to hemoglobin?

Answer 48

Carbaminohemoglobin ## Footnote It is transported to the lungs for CO2 release.

Question 49

What happens to CO2 binding in relation to H+s?

Answer 49

Facilitates dissociation of H+s and decreases pH ## Footnote This reaction helps regulate blood pH levels.

Question 50

What is the charge of 2,3-Bisphosphoglycerate (2,3-BPG)?

Answer 50

-5 ## Footnote This negative charge allows it to interact with positively charged amino acids in Hb.

Question 51

What is the effect of 2,3-BPG on hemoglobin conformation?

Answer 51

Favors T (deoxyHb) conformation ## Footnote This conformation has a lower O2-binding affinity.

Question 52

What happens in the absence of 2,3-BPG?

Answer 52

Positive charges on β-subunits repel each other ## Footnote This favors the R (oxyHb) conformation with higher O2-binding affinity.

Question 53

What does 2,3-BPG do to the O2 dissociation curve of hemoglobin?

Answer 53

Shifts it to the right ## Footnote This indicates a decreased affinity for O2.

Question 54

How can red blood cells adapt to deliver more or less O2?

Answer 54

By raising or lowering 2,3-BPG concentrations ## Footnote This mechanism allows for fine-tuning of oxygen delivery to tissues.

Question 55

What is the effect of carbon monoxide (CO) on hemoglobin?

Answer 55

CO binds to the Fe2+ ion in Hb with 220X greater affinity than O2, forming Carbon monoxyhemoglobin (reversible) ## Footnote CO binding to one or more heme sites favors the R form of Hb.

Question 56

How does CO binding affect the oxygen dissociation curve?

Answer 56

CO binding shifts the O2 dissociation curve to the left, allowing remaining sites to bind O2 with increased affinity ## Footnote This transition results in a change from a sigmoidal to a hyperbolic O2 dissociation curve.

Question 57

What are the potential consequences of carbon monoxide toxicity?

Answer 57

Toxicity can result due to hypoxia or direct cellular damage ## Footnote Hypoxia refers to a deficiency in the amount of oxygen reaching the tissues.