Haemoglobin Structure And Stereochemistry Of Oxygenation

Question 1

Biological importance of heme groups

Answer 1

• heme groups on Hgb and Myogb maintain supply of O2 essential for oxidative metabolism
• Myogb stores O2 and is reserve against O2 deprivation
• Hgb transports O2 to tissue and returns CO2 and protons to lungs

Question 2

Why do Cyanide and CO2 kill !?

What does tetrameric structure of hemoglobin permit

Answer 2

• they disrupt physiological function of heme groups

- permits cooperative interactions that are central to function

Question 3

What is a metalloprotein

Answer 3

-a protein with a metal prosthetic group ( function group covalently bonded to protein and essential for function)

Question 4

Describe structure of myoglobin

Answer 4

• single peptide chain folded into a tertiary structure with 1 heme group
• 8 alpha helixes connected by non helical regions
• interior R groups hydrophobic and exterior hydrophilic
• water soluble globular protein

Question 5

When is Fe added into heme group and what stabilizes it

Purpose or protein around heme group

Answer 5

• added during synthesis of proteins
• stabilized by hydrophobic residues in interiors of proteins
• protective environment that prevents oxidation of Fe2 into Fe3

Question 6

What is chelation

Answer 6

-binding of ions and molecules to metal ions by coordinate bonds

Question 7

How is Fe added to heme groups

Function of prosthetic group

Answer 7

• it is chelated by tetrapyrole ring system ( protoporphyrin X ) into ferroprotoporphyrin
• lose 2H and add Fe2
• responsible for carrying gases
• gives muscles and blood distinctive red color

Question 8

Describe atoms joined to Fe

Answer 8

1 4 N atoms from polyphyrin ring
2 2 histidines in heme binding pocket

• 5th coordinate site occupied by histidine via imidazole ring ( distal hist )
• 6th coordinate site occupied by H2 bonded O2 to hist for hinderance factors

Question 9

Position of Fe on heme group on oxygenated and deoxygenated blood

Answer 9

• flush with heme group

- lowered from heme group plane

Question 10

When do Myogb and Hgb bind to O2

Answer 10

-when it is in high conc ie the lungs

Question 11

Which globular protein would be more efficient in transporting O2 and why

Answer 11

• HgB as it does bind to O2 as tight as Myogb

- Myogb does not show cooperative binding and release of O2

Question 12

Which factor is important to Myogb and Hgb function

Answer 12

• affinity for binding O2

- Myogb has high affinity for O2 and can effectively store and release it especially when body is starved of O2

Question 13

Dangers of anaerobic exercise and how the body defends

Answer 13

• there is release of CO2 and lactic acid build up in the body
• Myogb and Hgb release O2 to protect against harsh effects

Question 14

What does oxymyoglobin do

Answer 14

/store O2

• utilize O2 by scavenging for NO ( bioactive nitric acid ) made by myocyte
• reacts with NO to form harmless nitrates and ferro myoglobin which is recycled through intracellular enzyme met myoglobin reductase

Question 15

How does body fight against Nitric acid

Answer 15

-oxymyoglobin eacts with NO to form harmless nitrates and ferro myoglobin which is recycled through intracellular enzyme met myoglobin reductase

Question 16

What happens when muscle is damaged

Answer 16

-there is releases of myoglobin which may flood in liver become toxic and cause renal failure

Question 17

Describe hemoglobin structure

Answer 17

• tetrameric each subunit of s protein chain with tightly associated with non-protein heme group
• chains arranged into alpha helixes and beta sheets joined in globin fold whose pattern make pockets that strongly bind to heme group

Question 18

Describe the types of Hgb , percentages and where dominant

Answer 18

1 Hgb A ( 97-97% ) tetrameric of a2b2. Normal that exists after birth

2 Hgb A2 ( 2-3% ) a2 and delta 2. Minor component found in blood after birth

3 Hgb F ( ~1% ) a2 and gamma 2. Predominant during fetal development

Question 19

What is HPFH and how does its come about

Answer 19

• hereditary persistence of fetal hemoglobin

- due to individuals who make Hgb F throughout their entire life even though it’s suppose to fall after birth

Question 20

What is allosteric Regulation and allosteric site

Answer 20

• regulation of a protein by binding of effector at site distinct from active site
• site at which effector binds and brings about conformational changes in protein

Question 21

Types of allosteric effectors and their effect

Answer 21

1 allosteric activator - enhances protein function

2 allosteric inhibitors- decrease or inhibit protein function

Question 22

Describe cooperative binding / release of Hgb

Answer 22

-as more O2 is bound to Hgb affinity for O2 increases and vice versa of one heme groups loses its O2 it’s easier for the other ones to do the same

Question 23

What is reduced Hgb

Where does CO2 bound on Hgb, how many and name of complex

Name of O2-Hgb complex

Answer 23

• Hgb that releases its O2
• not to Fe but to protein chain. 2 of them forming carbaminohaemoglobin
• oxyhemoglobin

Question 24

How is CO2 transported by blood

Answer 24

• either bound to RBC

- dissolved in blood plasma as CO2 or as HCO3

Question 25

What is 2,3-BPG and its effect and it binds to which molecule

Answer 25

• 2,3-Biphosphoglycerate
• negative allosteric effector ie decrease affinity of O2 by Hgb
• binds to deoxyhemoglobin as it has the central cavity to bind to it

Question 26

What does Hgb do at 20,40 and 100 mm Hg

When is O2 dissociation highest

Answer 26

• loses most of its O2
• still losing O2
• is saturated

-When pO2 is at that occurring in tissue

Question 27

Why does Hgb gain O2 in lungs

Cause of Hgb sigmoid Hgb-O2 shape

Answer 27

• alveolar capillaries interface has high O2 conc so they readily bind to it
• binding 1st O2 is difficult but facilitates binding of 2nd and 3rd but 4th also hard due to crowing of Hgb and natural tendency of Hgb to dissociate

Question 28

Factors shifting Hgb-O2 curve and what they do when high and low

Answer 28

Temperature - right / left 
2,3 BPG - right / left 
p( CO2 ) - right / left
p ( CO ) - left / right 
pH.        - left / right 
Type of HB - A Hgb ( right ) / F Hgb ( left )

Question 29

List levels of 2,3 BPG and where found

Answer 29

• 5mmol / L : normal blood

- 8 mmol/ L : individuals adapted to high altitude

Question 30

How is 2,3 BPG removed and it’s function

Answer 30

/in lungs O2 is so high that it is released

-binds to reduced de oxyhemoglobin to ensure it doesn’t bind to O2 it just released

Question 31

Describe Bohr’s effect

Answer 31

-decreased in pH decreases O2 affinity shifting graph to the right and increase in pH increases affinity shifting graph to the left

Question 32

How does temp affect affinity

Answer 32

-increase in temp causes conformational changes in shape and this reduces affinity

Question 33

How does Hgb type affect affinity

Answer 33

-F Hgb Doesn’t bind to 2,3-BPG due to the gamma chains so has greater affinity for O2 as compared to A Hgb

Question 34

How is O2 taken up by placenta

Answer 34

-at placenta there is high 2,3-BPG conc so A Hgb releases blood as it binds to 2,3-BPG and F Hgb will take it up

Question 35

How does pCO affect graph

Answer 35

• CO2 causes carbamino compounds to form which bind to Hgb forming carbuminohemoglobin reducing O2 affinity
• also it influences intracellular pH and causes Bohr’s effect

Question 36

How is CO2 carried in blood and %’s

Answer 36

• 5-10 as carbamino

- 80-90 as bicarbonate ions which release H+ increasing pH

Question 37

Effect of pCO on graph

Answer 37

• it competes for same binding sites as O2 and binds 240 times more readily
• but it increase O2 affinity of Hgb so Hgb won’t be able to readily release O2 to tissue shifting graph to the left when high conc
• excessive levels can cause hypoxaemia - reduced O2 carrying capacity of blood / O2 deficiency in arterial blood

Question 38

How to treat CO poisoning

Answer 38

-100% O2 therapy to facilitate dissociation of CO from Hgb