Final Exam - Heme Proteins

Question 1

Describe myoglobin’s function?

Answer 1

• Protein that stores and transports oxygen in muscles
• When O2 concentrations are low it releases O2 to muscles
• When O2 concentration are high, it holds on to O2
• Used to convert nitric oxide to nitrate in mitochondrial electron transport chain

Question 2

Describe hemoglobin’s function?

Answer 2

• Transports oxygen from lungs to tissue; high affinity for oxygen, low affinity for CO2
• Transports CO2 from tissue to lungs; high affinity for CO2, low affinity for O2

Question 3

Describe the iron structure of hemoglobin?

Answer 3

• Contains Fe²⁺ (ferrous)
• Has 6 coordination sites for binding
• Binding of ligands to the metal ion stabilizes the charge and helps it be soluble
• Forms octahedral complexes (AX6)

Question 4

How does hybridization allow for ligand binding and stability of the ferrous in hemoglobin?

Answer 4

Fe²⁺ has a electoron configuration of [Ar]4s⁰3d⁶
These orbitals can hybridize into sp³d² moving all of the electrons into the 3d orbintals. This now allows the iron to have 6 open binding sites that will stabilize the structure.

Question 5

What is a porhyrin?

Answer 5

Heterocyclic macrolide composed of four modified pyrrole subunits
Highly conjugated allowing for stability
Structure that is the base of the heme complex

Question 6

Define pi and sigma bonds?

Answer 6

Pi bonds form multiple bonds (double and triple bonds)
Sigma bonds form single bonds

Question 7

What specific porphyrin complex is used to create the heme molecule?

Answer 7

Protoporphyrin IX

Question 8

How does the porphyrin complex beome the heme complex?

Answer 8

The ferrous group is added by ferrochelatase

Question 9

Describe apoprotein and its role in hemoglobin?

Answer 9

Heme is hydrophobic and non-functional on its own
Apoprotein turns heme into the biofunctional heme protein by engulfing it
It also allows heme to bind to histadine-8 which is the 5th ligand, pulling the Fe below plane

Question 10

What is myoglobins structure?

Answer 10

Monomeric = 1 heme unit, 1 protein unit
Tertiary structure

Question 11

What is hemoglobins protein structure?

Answer 11

Quartenary protein made up of B1, B2, a1, a2 subunits - called a tetramer (4 heme subunits, 4 protein units)

Question 12

How is fetal hemoglobin different from an an adult?

Answer 12

Fetal hemoglobin is produced unitl 6 months of age and contains 2 gamma subunits and 2 beta subunits
It has a higher affinity for oxygen than adult hemoglobin

Question 13

What happens to the structure of hemoglobin when O2 binds to it?

Answer 13

O2 pulls the Fe back up into plane from where histadine-8 pulled it down

Question 14

What compound has a higher affinity for hemoglobin than oxygen?

Answer 14

Carbon monoxide (MO)

Question 15

How can we dteremine how much oxygen is bound to hemoglobin?

Answer 15

Oxygenated and deoxygenated hemoglobin will absorb different wavelengths of light, allowing us to know through computation what percentage of hemoglobin is bound and unbound (SpO2)

Question 16

Differentiate oxygen binding between myoglobin and hemoglobin?

Answer 16

Myoglobin:
* Non-cooperative binding (doesn’t have multiple binding sites)
* Higher affinity for oxygen - which makes it hold on to oxygen longer
Hemoglobin:
* Cooperative binding (multiple binding sites)
* Oxygen affinity increases as more oxygen binds

Question 17

What does a sigmoidal curve on a oxygen binding curve mean?

Answer 17

Reflects cooperative binding
The steep rise is evidence of increased affinty for oxygen with increased binding

Question 18

What is the T state of hemoglobin?

Answer 18

“Tense” state - no oxygen is bound, heme bidning sites are harder to get to, Fe+ is below plane

Question 19

What is the R state of hemoglobin?

Answer 19

“Relaxed” state - All 4 oxygen sites are bound and all of the heme Fe sites are in plane.

Question 20

Explain how the structure of hemoglobin changes when oxygen begins to bind?

Answer 20

As oxygen binds the hemoglobin protein it exhibts conformation changes which increases the affinity of oxygen binding by making the other other heme sites more accessable.

Question 21

Why does fetal hemoglobin have a higher affinity for oxygen than adult hemoglobin?

Answer 21

Fetal hemoglobin binds very weakly to 2,3-biphosphoglycerate (BPG)

Question 22

What does a leftward and righward shift mean on a oxyhemoglobin dissociation curve?

Answer 22

Rightward shift - decreased affinity for oxygen
Leftward shift - increased affinity for oxygen

Question 23

What is the role of BPG in adults?

Answer 23

• Binds only deoxygenated Hgb, stabilizing the Hgb structure
• Lowers oxygen affinity because favors T state of hemoglobin
• Increases CO2 unloading

Question 24

Compare BPG binding in fetal and adult Hgb?

Answer 24

Adult: BPG is binding to histadine rings via strong ion-ion bonds
Fetal: The BPG is further from binding sites, and the sites are no longer charged (OH-), so when it does bind it is ion-dipole.

Question 25

What are the 3 transport mechanisms for carbon dioxide?

Answer 25

• Dissolved gas
• Bicarbonate
• Bound to the hemoglobin protein (carbaminohemoglobin)

Question 26

What does the Bohr effect state?

Answer 26

Oxygen dissociation is altered by changes to the chemical environment including:
Increased temperature - Increases oxygens dissociation (rightward shift)
Lowered blood pH - Increases oxygens dissociation (rightward shift)
Increased PCO2 - increases H+ ion concentration

Question 27

What is the Haldane effect?

Answer 27

The same as the Bohr effect but pertains to CO2 instead of oxygen. All the factors would be inverse.

Question 28

Describe CO biding to hemoglobin?

Answer 28

CO binds 200-300 times stronger to hemoglobin than oxygen and prevents O2 from binding
This causes hypoxia from reduced oxygen delivery to tissues