Haemoglobin Structure And Stereochemistry Of Oxygenation Flashcards
Biological importance of heme groups
- 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
Why do Cyanide and CO2 kill !?
What does tetrameric structure of hemoglobin permit
- they disrupt physiological function of heme groups
- permits cooperative interactions that are central to function
What is a metalloprotein
-a protein with a metal prosthetic group ( function group covalently bonded to protein and essential for function)
Describe structure of myoglobin
- 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
When is Fe added into heme group and what stabilizes it
Purpose or protein around heme group
- added during synthesis of proteins
- stabilized by hydrophobic residues in interiors of proteins
- protective environment that prevents oxidation of Fe2 into Fe3
What is chelation
-binding of ions and molecules to metal ions by coordinate bonds
How is Fe added to heme groups
Function of prosthetic group
- 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
Describe atoms joined to Fe
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
Position of Fe on heme group on oxygenated and deoxygenated blood
- flush with heme group
- lowered from heme group plane
When do Myogb and Hgb bind to O2
-when it is in high conc ie the lungs
Which globular protein would be more efficient in transporting O2 and why
- HgB as it does bind to O2 as tight as Myogb
- Myogb does not show cooperative binding and release of O2
Which factor is important to Myogb and Hgb function
- affinity for binding O2
- Myogb has high affinity for O2 and can effectively store and release it especially when body is starved of O2
Dangers of anaerobic exercise and how the body defends
- there is release of CO2 and lactic acid build up in the body
- Myogb and Hgb release O2 to protect against harsh effects
What does oxymyoglobin do
/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
How does body fight against Nitric acid
-oxymyoglobin eacts with NO to form harmless nitrates and ferro myoglobin which is recycled through intracellular enzyme met myoglobin reductase
What happens when muscle is damaged
-there is releases of myoglobin which may flood in liver become toxic and cause renal failure
Describe hemoglobin structure
- 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
Describe the types of Hgb , percentages and where dominant
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
What is HPFH and how does its come about
- 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
What is allosteric Regulation and allosteric site
- 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
Types of allosteric effectors and their effect
1 allosteric activator - enhances protein function
2 allosteric inhibitors- decrease or inhibit protein function
Describe cooperative binding / release of Hgb
-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
What is reduced Hgb
Where does CO2 bound on Hgb, how many and name of complex
Name of O2-Hgb complex
- Hgb that releases its O2
- not to Fe but to protein chain. 2 of them forming carbaminohaemoglobin
- oxyhemoglobin
How is CO2 transported by blood
- either bound to RBC
- dissolved in blood plasma as CO2 or as HCO3
What is 2,3-BPG and its effect and it binds to which molecule
- 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
What does Hgb do at 20,40 and 100 mm Hg
When is O2 dissociation highest
- loses most of its O2
- still losing O2
- is saturated
-When pO2 is at that occurring in tissue
Why does Hgb gain O2 in lungs
Cause of Hgb sigmoid Hgb-O2 shape
- 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
Factors shifting Hgb-O2 curve and what they do when high and low
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 )
List levels of 2,3 BPG and where found
- 5mmol / L : normal blood
- 8 mmol/ L : individuals adapted to high altitude
How is 2,3 BPG removed and it’s function
/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
Describe Bohr’s effect
-decreased in pH decreases O2 affinity shifting graph to the right and increase in pH increases affinity shifting graph to the left
How does temp affect affinity
-increase in temp causes conformational changes in shape and this reduces affinity
How does Hgb type affect affinity
-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
How is O2 taken up by placenta
-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
How does pCO affect graph
- 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
How is CO2 carried in blood and %’s
- 5-10 as carbamino
- 80-90 as bicarbonate ions which release H+ increasing pH
Effect of pCO on graph
- 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
How to treat CO poisoning
-100% O2 therapy to facilitate dissociation of CO from Hgb
