Hemoglobin 2 Flashcards
Describe the globin protein structure
- The globin protein monomer is mostly composed of a-helix
- A few bends or turns are present
- Globin is an unusual structure protein in that it is void of B-sheet
How is iron ion (ferrous 2+) is protected ?
Iron ion (ferrous 2+) is protected by porphyrin ring and buried deep in the globin protein
Ferrous iron,2+ is protected by porphoryn ring, why is this important?
- It sets up a system where the oxygen molecule can enter/leave the hemoglobin in a defined path which is good since it reactive( might be released as superoxide without said system)
- Superoxide- O2+e-( superoxide is a free radical)
What is myoglobin designed to do?
Store oxygen in the cell, and deliver to the mitochondria when needed
What is the shape of the myoglobin dissociation curve?
The shape of the curve is hyperbolic
What is the importance of conservation of key amino acids?
This ensures correct shape, and function
Give examples of “Conservations of important amino acids ensures correct shape, and similar function”
Sperm whale myoglobin and human B-globin have a very similar structure despite primary sequence is remarkably different
Give the structure of human hemoglobin
- is a tetramer of 4 polypeptide chains
- Hemoglobin A, is a pair of identical aB divers (a2B2 heterodimers)
- Heme groups are widely spaced
What type of interactions are hemoglobin capable of?
Extensive interactions between the subunits
-Hydrophobic
- Ionic - hydrogen bonds
How much oxygen can hemoglobin hold?
4 globin monomers so each carries a molecule of oxuygen
So 4 O2
Why is hemoglobin a heterotetramer?
it is a a2B2 tetramer, meaning it has a a1, B1, a2 and B2 polypeptides
Describe the associations between the aB peptides
The aB peptides that form a dimer held together very tightly
-they don’t change, they stay tightly linked together
The two dimers associate with each other, but may shift slightly
-this structural change explains how O2 affinity may be regulated
How is affinity for O2 regulated?
Between both aB dimer 1 and aB dimer 2 there are hydrogen-bonds, ion-dipole bonds and ionic interactions -in the form of deoxyhemoglobin it is in a tautomeric state or “T”
As O2 binds to hemoglobin,/oxyhemoglobin forms, which is a much more relaxed form, it breaks the hydrogen and ionic salt bridges
Describe the interactions between each a and B polypeptide in hemoglobin
Many hydrophobic interactions exist between aB peptides to form a strong dimer, very strong LH attached to each other
Of course, some hydrogen bonds and ionic salt bridges also
What amino acids can stabilize the hydrophobic interactions of the a-globin B chains to form the aB dimers?
The branched chain amino acids- valine, leucine and isoleucine
Amino acids with aromatic side chains-phenylalanine, tyrosine and tryptophan
Aldo methionine, proline, glycine and alanine
Why is histidine so important to hemoglobin?
Histidine is the only common amino acid that has an ionizable side chain whose pKa is close to physiological pH and can be modulated
Allows Hb to do two very important things:
- Help to buffer the pH of the blood by absorbing protons.
- Regulate O2 affinity in response to pH
How is the pKa of histidine adapted for human buffering?
The pKa of histidine is around 6 but within the hemoglobin structure, the pKa is pushed to around 7. This is a more physiologically useful buffer
Describe the difference in shape in the porphyrin ring in an oxygenated vs. deoxygenated form
Deoxygenated- when Fe or heme is deoxygenated, porphyrin ring is puckered, heme is domed(nonplanar)
Oxygenated - When Fe or heme is oxygenated, porphyrin ring is planar, heme is planar and Ferrous ion comes into the plane
How does O2 binding change the shape of hemoglobin?
- Upon O2 binding, the heme ring assumes the more planar shape which tugs on the proximal hemoglobin which then tugs on the alpha helix which then changes the shape of the globin monomer
- in hemoglobin, this “tugging” can be communicated to the other subunits to change the shape of the tetrameric protein
Does binding of oxygen affect the shape the same way as in hemoglobin?
No, binding of oxygen doesn’t have this effect as myoglobin has only one polypeptide, so it has nothing to communicate to
Why is the oxygen -dissociation chrve a sigmoidal curve?
Cooperative ligand binding creates a sigmoidal curve because with every binding of an oxygen molecule, the affinity for binding of the next globin increases
What is the heme prosthetic group?
Porphyrin ring with a ferrous iron in the center
What is a P50?
The pressure at which 50% of O2 binding sites are saturated with oxygen
What is the p50 of myoglobin?
The p50 of myoglobin is about 1 mmHg, this does not change
What is the p50 of Hb at pH 7.4?
At pH 7.4, p50 of Hb is about 26 mmHg, this changes with pH
Differentiate 2,3 BPG level between a normal person and a person adapted to high altitudes. Why the trend?
Normal= 2,3 BPG-5mmol
Adapted to altitudes= 2,3 BPG-8 mol
Decrease in affinity for release of oxygen