Hemoglobin and myoglobin

Question 1

Polar gases (e.g. HS and NH3) are more soluble in water.

Nitrogen, O₂, and CO₂ are

Answer 1

nonpolar

insoluble in water; they’re transported via hemoglobin and myoglobin

Question 2

What causes hemoglobin (Hb) to bind O2 in the lungs but release it at the tissue?

Answer 2

Lungs have a higher pH

At the tissues, Hb picks up CO₂ and H+ to deliver back to the lungs

Question 3

Which binds O₂ more tightly - Hb or Mb?

Answer 3

Mb binds to O2 more tightly

Its affinity is unaffected by pH change or modifying molecules

Question 4

Heme is a prosthetic functional group in both Hb and Mb. What is its structure?

Answer 4

Protoporphyrin IX ring with a ferrous ion (Fe²⁺) at its center.

The Fe2+ makes 4 bonds to the ring, a 5th bond to a His, and a 6th bond to a single molecule of O_2. It can move in or out of the plane of hte ring

Question 5

While both Mb and Hb are similar and have a heme group in the center, what is thei rmajor difference?

Answer 5

Mb is a monomer

Hb is a heterotetramer: 2 a-globin subunits, 2 B-globin subunits ; each subunit has a central heme group

Question 6

equilibrium dissociation constant (Kd)

Answer 6

[ligand] at which half of the available ligand binding sites are occupied.

It’s essentially Km - the higher Kd, the lower affinity

Question 7

The binding curve for Mb is ___, which suggests that Mb has

Answer 7

hyperbolic, sugesting that Mb has only one binding site for its ligand (O₂).

As the pressure of O₂ increases, binds very rapidly to Mb until binding sites become limiting.

Question 8

The Kd of myoglobin is called

Answer 8

P₅₀

Question 9

The shape of Hb’s binding curve is ___, indicating ___

Answer 9

sigmoidal, indicating cooperative binding for O₂ subunits

Binds slow at first, but as the O₂ pressure increases, binding rate increases until they all get filled

Question 10

A curve shifted to the right signifies

Answer 10

higher Kd –> weaker affinity

That’s why Hb’s curve is shifted to the right

Question 11

Hb’s tense vs relaxed state

Answer 11

R state: The His is positioned such that the Fe²⁺ is in the plane of the ring and has a high affinity for binding O₂

T state: The His is positioned such that it pulls the Fe²⁺ out of plane; lower O₂ affinity

Question 12

__ bonds are broken when Hb switches from R state to T state.

Answer 12

8 bonds = 6 are interchain between diff subunits; 2 are intrachain

Question 15

How does the transition from T to R state occur?

Answer 15

Each O₂ that binds one of the heme groups breaks 2 of the ionic bonds, making it easier for the next Fe²⁺ to bind O₂​

This goes on until all 4 subunits bound an O₂

Question 16

What molecules affect O₂ binding in Hb and how?

Answer 16

• Increases Hb’s affinity for O₂
  
  • O₂
  • CO
• Decreases affinity
  
  • H+ (acidity)
  • CO₂
  • BPG

^{Things that increase affinity shift the curve to the left; decreasing affinity shfits right}

Question 17

Why does H+ and lower pHs decrease Hb’s O2 binding affinity?

Answer 17

It favors ionization and strengthens the ionic interactions of the T state

Question 18

When O₂ enters the plasma from the tissues, it can have one of 3 fates:

Answer 18

• 10% dissolves in the plasma and goes to the lungs
• In the RBC, 23% forms an adduct with hemoglobin –> carbaminohemoglobin
• In the RBC, ~70% is converted with water into bicarbonate (HCO₃^-) and H+ by carbonic anhydrase.
  
  • –> HCO₃^- and H+ are transported to the plasma, then lungs where they’re converted back to CO₂ and water
  • H+ acidifies the system to decrease O₂ binding affinity

Question 19

How does CO cause flu-like symptoms (headache, nausea, vertigo), seizures, coma, and death?

Answer 19

• Binds Hb MUCH more tightly than O₂ and doesn’t let go
• Stabilizes the R state, which prevents O₂ from being released into the tissue

Tx: pure oxygen

Question 20

Methemoglobinemia

Answer 20

• Fe²⁺ oxidation to Fe³⁺ –> methemoglobin (MetHb), which won’t carry O₂
• Death; Infants will get blue baby syndrome
• Causes:
  
  • Exogeneous oxidizing drugs (benzocaine, dapsone) increases
  • Nitrate-containing compounds (bismuth nitrate) or well water containing ntirates

Question 21

What is the strongest modifier of O₂ binding affinity?

Answer 21

2,3-Bisphosphoglycerate (BPG) from glycolysis

• Decreases affinity of Hb for O₂ so tissues can work

Question 22

What happens when someone living at sea level travels to the mountains?

Answer 22

Their BPG is too low –> Hb is only 87% saturated in the lungs, so not enough O₂ will get into the tissues

Tiredness, dizziness, nauseous

After a few days, you adapt by increasing you BPG

Question 23

Adult hemoglobin vs fetal

Answer 23

Adult: 2 a-globin subunits and 2 B-globin

Fetal: 2 a-globin subunits and 2 y-globin subunits

• y-subunit: 2 serines replace 2 His in the B subunits –> HbF is lower affinity for BPG and thus a higher affinity for O₂

That way, if mom experiences a rapid decrease in oxygen, fetus will be spared