Protein Structure Flashcards
What are the 2 functions of Red Blood Cells?
- transfer O2 from lungs to tissue
- transfer CO2 from tissue to lungs
What were the first proteins to be crystallised?
Haemoglobin and Myoglobin
How were Haemoglobin and Myoglobin studied?
via ultracentrifugation
Where is myoglobin found in vertebrates?
- skeletal muscle
- heart muscle
How many subunits does myoglobin have?
1
What does myoglobin facilitate?
rapidly respiring muscle tissue
Is the rate of O2 diffusion slow?
Yes
Why is the rate of O2 diffusion slow?
due to the solubility of O2
Does myoglobin increase or decrease the solubility of O2?
increase
Why is oxygen storage via myoglobin greater in whales and seals?
they can slowly release O2 in their bodies
What is the structure of the “haem complex” in myoglobin?
two histidine residues (proximal and distal) anchor to haem
What is the ring around Fe called?
polyporphyrin
What is “Histidine”?
an amino acid with a side chain (imidazole)
What does “Histidine” have a tendency of binding?
metal
What genes encode haemoglobin?
globin
How many subunits does haemoglobin have?
4 (2 alpha, 2 beta)
What type of oligomer is haemoglobin?
tetramer
What is an “oligomer”?
a molecule consisting of a few similar repeating units
What protein contains iron?
ferritin
Is the synthesis of haem and globin synchronised?
yes
Where is haem synthesised?
mitochondria
Where is globin synthesised?
polyribosomes
Do what do mature red blood cells not contain?
mitochondria
What does Hb carry excluding O2?
- CO2
- H+
What is haem derived from?
protoporphyrin IX
Can Fe3+ bind O2?
No
What is the reduced form of iron?
Fe2+
What is the oxidised form of iron?
Fe3+
What is Fe3+ bound to globin?
methemoglobin
What number ligand does protoporphyrin bind O2 to?
6th
What is the 5th ligand?
histidine F8
What bound to the proximal side of Fe2+?
His F8
What bound to the distal side of Fe2+?
oxygen
What 4 molecules outcompete O2?
- CO
- NO
- CN-
- H2S
What can increased methemoglobin be caused by?
- drugs
- environmental agents
What does the oxygen dissociation curve of Mb and Hb look like?
compare to reference image
What is the
binding of O2 abbreviated as?
YO2
What is the formula of YO2?
PO2/ Kd+pO2
What do the Hb subunits independently compete for?
the first O2 to bind
What does it mean if YO2 is close to 1?
3 subunits are occupied and the 4th is independent of the other site
What is “D-2,3-Bisphosphoglycerate (BPG)”?
- allosteric effector
What is the function of “D-2,3-Bisphosphoglycerate (BPG)”?
- modulates (regulates) the affinity of Hb for O2
- providing control and adaptation to environmental factors
What does high altitude mean for the abundance of BPG?
increased
What is “BPG” also known as?
DPG
What 4 factors affect the position of Hb-O2 dissociation curve?
- [BPG]
- pH
- CO2 in RBCs (Bohr effect)
- structure of Hb
What is “stripped Hb”?
Hb without BPG
How is “stripped Hb” produced?
conc. NaCl
What causes a right shift in the dissociation curve?
- high BPG
- high H+
- high CO2
- HbS (Sickle Cell)
What does a right shift mean?
easy O2 delivery (improves release of O2)
What causes a left shift in the dissociation curve?
- low BPG
- HbF (fetal Hb)
What does the “picket-fence Fe(II)-porphyrin complex” mean?
Fe2+ bound within the porphyrin ring is surrounded
by side-chains of the porphyrin molecule to form a “fence” like structure that protects the iron from oxidation
Can oxygen bind to tense Hb?
not well
What binds to tense Hb?
- CO2
- H+
What is the maximum capacity of Hb for O2?
4
Where are the interactions between the alpha and beta subunits occurring in DeoxyHb?
alpha1/beta1
Where are the changes between the alpha and beta subunits occurring in oxyHb?
alpha1/beta2
What subunits are unchanged in oxyHb (relaxed form)?
alpha1/beta1
What occurs when oxygen binds to Hb?
conformational shape change
How does Hb go from T state to R state?
binary switch
What drives the T->R transition?
energy in the formation of Fe-O2
As the lungs become more acidic, what does it mean for O2?
it does not bind as well
At higher pH (basic) what is promoted?
tighter binding of O2 to Hb
At lower pH (acidic) what is promoted?
easier release of O2 from Hb
What is the equation linking the Bohr effect and CO2?
CO2 + H20 HCO3- + H+
What enzyme catalyses this reaction in erythrocytes?
carbonic anhydrase
How does HCO3- affect the pH?
increases
What does the increased pH do to HCO3-?
decreases the binding of O2
What does the decreased binding of O2 mean for Hb?
it’s in T form
Where is the forward reaction (CO2 + H20->HCO3- + H+) driven?
capillaries
Where is the backward reaction (HCO3- + H+-> CO2 + H20) driven?
lungs
What does deoxyHb bind CO2 as?
carbamate
High [CO2] in capillaries stimulates Hb to what?
release O2
What other ion affects the affinity of Hb for O2?
Cl-
What is Sickle Cell Anaemia (SCA)?
a genetic disease that affects Hb
What individuals are affected (diseased) by SCA?
homozygous
What individuals are not affected (carriers) by SCA?
heterozygous
What does SCA cause?
defective Hb (they stick together causing RBCs damage)
Heterozygous individuals are protected from what? (By having SCA)
malaria
What DNA mutation occurs in HbS?
point mutation
What does the mutation cause in HbS?
glutamate (glu) replaced by valine (val)
Why is this protein mutation drastic?
glu is negatively charged, val has no charge
Is Val is hydrophobic or hydrophilic?
hydrophobic
