Proteins: Myoglobin & Hemoglobin (Chapter 6) Flashcards
What does Heme consist off?
4 pyroles linked via Methyne bridges.
What do we find inside heme?
Fe2+
What happens if there is oxidation of Fe2+/Fe3+?
it destroys the biological activity of myoglobin and hemoglobin.
discuss myoglobins structure
Consists of 8 Right handed Helices.
On the surface we have polar AA
on the interior we have Non-polar AA apart from two (His E7, HisF8)
Discuss HisE7 and HisF8 and the iron ion
Heme lies between the helices E and F.
Iron is bound on it’s 5 co-ordination position by the nitrogen in the imidiazole ring of Histidine F8.
What happens in terms of movement of Amino Acids when oxygen binds to fe2+?
Initially fe2+ lies 0.03nm outside of the ring.
when oxygen binds to it, it pulls it towards the ring, which causes movement of His F8 which causes movement of the amino acids connected to it.
What subunits make up haemoglobin off:
1) Adult
2) Fetal
3) Sickle cell
1) a2b2
2) a2y2
3) a2 b(s)2
What is co-operative binding?
advantage of co-operative binding?
When one molecule of Oxygen binds to Haemoglobin, the other readily binds to it with higher affinity.
Advantage:
Allows oxygen to bind at p(o2) of lungs
and deloads at tissue.
What does P50 show?
What does comparison of p50 of fetal and adult haemoglobin show.
P50 shows the p(O2) of which the heme is half saturated.
Fetal p(o2) = 20 adult p(o2) = 26 Lower p(o2) means higher affinity to oxygen.
When does synthesis of b subunit in haemoglobin begin?
Begins in 3rd trimester.
How does oxygenation explain conformational change?
- Binding of oxygen causes shifting of iron towards plane of heme.
- This pulls His F8 which pulls the other residues.
- This ruptures salt bridges so Hemoglobin is in R-state.
1) What is carbamation?
2) How does Carbamation affect the state of haemoglobin?
1)Method of Hemoglobin carrying co2.
Co2 + Hb-NH3+ —> Hb-NH-COO + 2H+
Carbamate forms with terminal amino
2)Carabamate formation causes changing from positive to negative charge, which favours salt bridge formation so T-form.
Equation for formation of Bicarbonate Ion
Co2 + H20 H2Co3 —–> HCO3- + H+
first step catalysed by carbonic anhydrides.
1) How many protons does deoxyhaemoglobin bind for every oxygen released?
2) Important of deoxyhaemoglobin binding to protons?
1) proton for every 2 oxygen released.
2) Buffer effect
What stabilises the T-state?
- carbamation
- Low pH
- 2-3BPG
What is the Bohr effect?
- Deoxyhemoglobin binds to protons.
- takes them to the lungs.
- released for O2.
- The proton combines with bicarbonate ion to form acid, this then released as co2.
How do protons arise?
arise when there is rupturing of salt bridges..
When is 2-3 BPG formed?
and where does it bind?
2-3 BPG is formed when there is low p02 in the tissues.
In T-state it binds btw the H-Helices of the B subunits.
What is the effect of BPG?
How does it cause this?
BPG stabilises the T-state. It does this by forming salt bridges to terminal amino via: -Val -His -Lys
How does 2-3BPG’s effect differ in fetus?
It binds weakly compared to in Adults.
Instead of His, it binds via Ser.
This explains why Fetal Hemoglobin has higher affinity than Adult.
1) What is Methomoglobin?
2) What causes this?
1)Fe3+ instead of F2+ So cannot bind to O2. 2)-Sulfonamides -Hereditary - Reduced activity of methemoglobin (which reduces f3+ to fe2+)
What do we find in Haemoglobin M?
His F8 has been replaced for Tyrosine.
What do we find in Sickle Cell Anemia?
Valine has been replaced for Glu6
This generates a hydrophobic sticky patch.
What is Myoglobinuria?
Following a massive crush injury to skeletal muscle.
Myoglobin may be found in urine.
How can we detect myoglobin in the Urine?
-Assay of serum enzymes.
