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
