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What type of bond is heme bound to hemoglobin by? (normally)
What type of protoporphyrin is found in hemoglobin? What are the sidechains?
Protoporphyrin IX; 4 methyl, 2 vinyl, 2 propionate
How does protoporphyrin become heme?
It bind iron (Fe+2)
What number chromosome carries the alpha-type gene for globin? What is the fetal version? How about beta type globin? What are some other versions of the beta-type gene?
- alpha-type: chromosome 16, fetal version: zeta
- beta-type: chromosome 11, other beta versions: delta, gamma, epsilon
How many exons/introns are in each globin gene?
3 exons and 2 introns
Know the type of globin expressed at various stages of fetal development. Draw the graph birth months vs. % of total globin for both type alpha and type beta.
- draw the graph
- for type alpha: zeta is first trimester of fetal develpment. Then alpha globin rises and takes over into adulthood.
- for type beta: epsilon at first trimester. Then gamma takes over until birth at which point it starts to drop. beta globin increases at birth and takes over at 3 months almost completely. A bit of delta globin appears and birth and remains at low levels.
What globin chains are in each of the following? What is the developmental stage (embryo, fetus, adult)? HbA1, HbA2, HbF, HbGower1, HbGower2, HbPortland
- HbA1: alpha2 beta2 Adult
- HbA2: alpha2 delta2 Adult
- HbF: alpha2 gamma2 Fetus
- HbGower1: zeta2 epsilon2 Embryo
- HbGower2: alpha2 epsilon2 Embryo
- HbPortland: zeta2 gamma2 Embryo
How is beta globin converted to HbA1C? Is HbA1C a result of a gene? What other molecule needs to be present? What type of bond is made? What is it a measure of?
It is the stable adduct formed by an amadori rearrangment of an aldimine to a ketimine. Aldimine is formed when glucose is added to the N terminal amino group of a beta chain. This is not a result of a gene but a non enzymatic post translational modification. Glucose needs to be present. This glycation bond is a measure of long term glucose levels in diabetics.
Where are coordinate positions 5 and 6 in heme? What they important for?
On each side of the protoporphyrin face. They are important for binding hemoglobin and oxygen.
What happens to free iron (Fe2+) in the presence of oxygen? What role does hemoglobin play? Why is this important for oxygen binding?
Fe2+ oxidizes to Fe3+ (ferric). Normally Hb prevents iron oxidation by keeping the heme in a hydrophobic environment (pocket). Allows reversible binding of oxygen by Hb.
Terminology: name the Fe2+ and Fe3+ forms
- Fe2+: Ferrous, heme, Hb, Mb
- Fe3+: Ferric, hemin, metHb or ferriHb, metMb
What are the structureal differences between Hb and Mb? Where does each reside?
Hb is a tetramer in the RBC; Mb is a monomer in the muscle; both are oxygen carriers
What are some physiological properties of Hb that make it a good oxygen carrier?
- 1. very high solubility in water. partly due to its spherical shape and polar surface residues.
- 2. can carry large amounts of oxygen. ~20ml O2/100mL of blood (free oxygen is only 0.3ml O2/100mL of water)
- 3. Uptake and release of oxygen is regulated by partial pressure. Hb binds O2 in the lungs and release O2 in the tissues.
- 4. Hb is a good buffer. This is important as many biochemical processes involve release of H+
Are the primary amino acid structures of Hb and Mb identical? How about the tertiary conformation?
The primary a.a. structure is NOT identical. Only 64 base pairs in common. But the tertiary structure is similar.
What does the proximal histadine bind? What about the distal histadine?
- Proximal HIS binds Heme
- Distal HIS binds Oxygen
What is the quartanery structure of Hb?
Dimer of dimers (alpha-beta dimer)
What are the X and Y axis of the Os dissociation curve? Where is venous and arterial pressure on the axis? What is P50?
- X axis: partial pressure of oxygen (torr 0-100)
- Y axis: Y fractional saturation (0-1)
- Venous pressure is to the left.
- Arterial pressure to the right.
- P50 is partial pressue at which 50% of the molecules are saturated.
On a dissociation curve, what does left shift and right shift generally mean? Orient Hb and Mb by this definition.
- Left shift: higher affinity for O2 (Mb)
- Right shift: lower affinity for O2 (Hb)
On a dissociation curve, what does hyperbolic versus sigmoidal generally mean? What is the Hill coefficient? What is nH of Hb and Mb?
- Hyperbolic: less cooperative binding of O2
- Sigmoidal: more cooperative binding of 02
- Hill coefficient is a number for cooperativity. nH=1 no cooperativity, nH>1 cooperativity
- nH(Hb)=2.8; nH(Mb)=1.0