Hemoglobin 3

Question 1

Contrast the taut state and relaxed state of hemoglobin

Answer 1

Taut state-when fractional saturation is low and no oxygen is bound, the hemoglobin is held together by ionic bonds

Relaxed state- saturated with oxygen, conformational changes break hydrogen bonds ionic bonds to be broken to increase affinity to grab oxygen

Question 2

What is cooperative ligand binding?

Answer 2

Binding of one oxygen molecule promotes the binding of another oxygen molecule

Question 3

Why can we say an oxygen molecule is a positive allosteric regulator?

Answer 3

Because binding of a oxygen molecule at one site increases affinity at another site

Question 4

What is the Bohr effect?

Answer 4

The O2 dissociation curve shifts to the right with decrease in pH (recall that increased PCO2 leads to decreased pH)

Question 5

How does pH affect oxygen affinity in hemoglobin?

Answer 5

As pH decreases, a higher pO2 is needed to bind the oxygen molecule/ reduced of oxygen for hemoglobin/ rightward shift in oxygen saturation curve

Question 6

Evaluate the shape of myoglobin dissociation curve and their functions

Answer 6

Myoglobin has a higher affinity for oxygen binding as it delivers oxygen to muscles

Hemoglobin may release oxygen (hence lower affinity and rightward shift on graph) which binds to myoglobin and can deliver the oxygen to hemoglobin

Question 7

What is Carbonic anhydrase?

Answer 7

It promotes the formation of carbonic acid from CO2

Question 8

Explain how Caron anhydrase supports life

Answer 8

The dissolving of CO2 into water is spontaneously fast, but nit fast enough to support life, Carbon anhydrase speeds this up

Question 9

How does formation of bicarbonate ion cause formation of taut hemoglobin?

Answer 9

• protons form/pH drops when bicarbonate forms
• Protonation of His side chains on Hb, forms positive charges
• This allows for addition of additional salt bridges
• this stabilizes the taut form of Hb
• Promotes O2 delivery to tissues

Question 10

What happens when carbon dioxide reacts with amino terminus of alpha-chains?

Answer 10

Allows formation of additional salt bridges, and also the release H+ ions to strengthen the Bohr effect

Question 11

What does CO2 react with the amino terminus to create?

Answer 11

NH2R + CO2 = NHR-CO2- + H+

Question 12

What forms 2,3 Biphosphoglycerate “

Answer 12

Formed from a side reaction in glycolysis

Question 13

What is the significance of 2,3 bispohosphoglycerate?

Answer 13

2,3 BPG is a potent regulator of Hb oxygen affinity

Negative charge on OPO3 ^2- slips between aB dimers to form salt bridges with with histidine amino acids (which can be differentially protonated, depending on pH of the solution)

Question 14

What kind of charge does 2,3 BOG have?

Answer 14

There are negative charges on a very small molecule

Question 15

Summarize all the functions of 2,3 BOG in hemoglobin

Answer 15

Promotes formation of taut state; decreases O2 affinity for Hb:

• 2,3 BPG allows the formation of additional salt bridges between the two aB dimers
• At the interface between the two aB dimers
• This creates a driving force for Hb to assume the deoxyHb structure(taut form)
  
  • promotes O2 unloading

Question 16

What kind of allosteric effector is 2,3 BPG? Why?

Answer 16

A negative allosteric effector

It causes a rightward shift and a sigmoidal curve is impossible without 2,3 BPG (hyperbolic)

Question 17

How do high altitude athletes have a different oxygen affinity?

Answer 17

High altitudes cause lower oxygen affinity of Hb to promote unloading

Question 18

What are the allosteric effects?

Answer 18

Regulation of O2 delivery by Hb depends on allosteric (“other site”) effectors:

• pO2
• pH of environment
• pCO2 (which influences pH, and taut/relaxed state
• 2,3BPG availability
• temperature increases thermal energy (exercises ) causes a rightward shift and O2 leaves

Myoglobin not regulated this way

Question 19

Where should O2 affinity be high?

Answer 19

In the lungs to promote binding to Hb

Question 20

Where should O2 affinity be low?

Answer 20

In tissues where they need to be released

Question 21

Summarize the actions in the lung that affect oxygen affinity as CO2 is released

Answer 21

• CO2 and 2,3 BPG are pushed out
• As CO2 is exhaled, pH goes up
• Protons come off His amino acid

Question 22

Summarize the actions that affect Oxygen affinity as O2 binds to hemoglobin

Answer 22

• High partial pressure of O2 forces itself onto ?Hb
• As the animal exhales, CO leaves the body, raising the pH
• Saturated O2 forces 2,3 BPG off of Hb
• As 2,3 BPG comes off of Hb, protons must leave as well( as they lose their negative charge partner)

Question 23

What drives O2 loading in lungs?

Answer 23

High partial pressure of O2 drives the loading of O2 in the lungs

Question 24

Why is CO2 thought to be a volatile acid?

Answer 24

It can leave the body as a gas

Question 25

How does CO2 leave/exhaled through the lungs?

Answer 25

- Carbonic acid decomposes to form CO2 which is exhaled, to raise the pH - Also, CO2 bound to N-terminal end of the alpha-globin subunits is released

Question 26

What promotes offloading in tissues?

Answer 26

Low pO2, lower pH and the presence of 2,3 BPG

Question 27

Contrast CO binding with O2 binding

Answer 27

- CO reversible binds to the Fe2+ the same way that O2 does - In free heme, (no protein), CO binds 20,000-25,000 - free heme binds preferably to CO 25,000X more tightly than O2

Question 28

Contrast CO binding with feee heme with homoglobin

Answer 28

When in the hemoglobin protein, the affinity of Hb for CO is reduced to approximately 200-250x the affinity for O2 In heme- CO binds 20,000-25,000

Question 29

How does CO bind to Hb?

Answer 29

- Hb forces CO to bond at an angle - Reduces the CO to Fe bond strength - Now it is only about 200x stronger than oxygen - CO binding to Hb is stronger than O2 binding, but is now reversible(we would die otherwise)

Question 30

What type of hemoglobin is carboxy hemoglobin HbCO?

Answer 30

CO + Hb= HbCO

Question 31

How does CO binding affect O2 binding?

Answer 31

- CO causes a relaxed Hb strongly, preventing 2,3 BPG from entering - causes holding onto too O2 tightly preventing O2 from leaving

Question 32

How much HbCO is fatal?

Answer 32

50 to 60%

Question 33

How can high HbCO be treated?

Answer 33

- O2 therapy( 100% oxygen) - higher pressure - hyperbaric medicine

Question 34

Describe the structure-function of fetal hemoglobin

Answer 34

- Has a few less histidine amino acids at the dimer interface - Causes less binding affinity for 2,3 BPG - so fetal hemoglobin has a stronger oxygen affinity