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function of hemoglobin
picks up oxygen in the lungs (high oxygen partial pressure/concentration) & delivers it to tissues (low oxygen partial pressure/concentration)
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function of arteries
carries oxygenated blood to tissues (for the most part)
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function of veins
carries deoxygenated blood (for the most part)
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Why have we evolved an elaborate oxygen transport system?
Oxygen is insoluble & cannot dissolve in the bloodstream at high concentrations, thus they need to be bound to a transport protein such as hemoglobin
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3D shapes of hemoglobin & myoglobin
- Hemoglobin: tetramer (4 subunits, quaternary interaction).
- Myoglobin: monomer (1 subunit).
(See slide #3)
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A subunit (for both hemoglobin & myoglobin) has __ alpha helices & can bind __ oxygen molecule(s)
8; 1
(Hemoglobin has 4 subunits so in total it binds 4 oxygen molecules)
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function of myoglobin
used by muscle cells to transport oxygen to mitochondria
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functional groups of a prosthetic heme group
- methyl (CH3): 4 total.
- vinyl (has =CH2): 2 total.
- pyrrole ring (N pentagon): 4 total.
- propionate (has COOH): 2 total.
(see slide #4. NEED TO BE ABLE TO RECOGNIZE STRUCTURES)
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Where do coordinate covalent bonds occur on a hemoglobin?
Coordinate covalent bonds include both pure & polar covalent bonds: Within the prosthetic heme group, there is C-C, N-C, & N-Fe. The N from the proximal Histidine binding to Fe is also considered a coordinate covalent bond.
(See slide #5)
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Where do favorable electrostatic interactions occur on a hemoglobin?
Oxygen binding to Fe
(See slide #5)
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Where do hydrogen bonds occur on a hemoglobin?
NH from a distal Histidine binding to the oxygen molecule that is bound to Fe
(See slide #5)
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The __ state occurs in veins
T (deoxygenated)
(See slide #3)
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The __ state occurs in arteries
R (oxygenated)
(See slide #3)
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In the __ state, there are 5 coordination contacts to the iron ion
T (deoxygenated)
(See slide #6)
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In the __ state, there are 6 coordination contacts to the iron ion
R (oxygenated).
The oxygen creates the 6th coordination contact.
(See slide #6)
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In the __ state, the iron ion is in a bulged conformation
T (deoxygenated)
(See slide #6)
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In the __ state, the iron ion is in a NON-bulged conformation
R (oxygenated)
(See slide #6)
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In the __ state, the inter-tetrameric cavity widens
T (deoxygenated)
(See slide #3)
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In the __ state, the inter-tetrameric cavity narrows/constricts
R (oxygenated)
(See slide #3)
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In the __ state, hemoglobin is bound to 2,3-BPG
T (deoxygenated)
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In the __ state, hemoglobin is NOT bound to 2,3-BPG
R (oxygenated)
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subunits of hemoglobin
4 subunits: alpha1, beta1, alpha2, beta2
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Why is hemoglobin binding to oxygen considered positive cooperativity?
It is multimeric (many subunits) so one subunit influences other subunits to bind to the ligand. Oxygen release also involves cooperativity.
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Myoglobin has a __ curve
hyperbolic - indicative of a single subunit. This shows a strong O2 binding state in both tissues & lungs. Myoglobin will hold onto most of the oxygen.
(See slide #7)
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Hemoglobin has a __ curve
sigmoidal (s-shaped) - indicative of multiple subunits. This shows a weak binding state in tissues & a strong binding state in lungs
(See slide #7)
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At a normal temp, __ degrees Celcius, the pH would be __ & there would be __ BPG
37; high (7.40); low (4-5mM)
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At a higher temp, __ degrees Celcius, the pH would be __ & there would be __ BPG
>37; low; higher (8mM)
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How is CO2 generated from our bodies?
One common route is from glucose catabolism (or oxidative breakdown in glycolysis), in which Glucose produces Pyruvate which then produces Acetyl CoA + CO2
(NEED TO KNOW THE STRUCTURES OF PYRUVATE & ACETYL COA)
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A right-shifted sigmoidal curve indicates __ while a left-shifted sigmoidal curve indicates __
Right: oxygen releasing faster (lower affinity to oxygen), lower pH (7.2), increase in BPG (8mM), increase in temp (>37 degrees)
Left: oxygen releasing slower (higher affinity to oxygen), higher pH (7.4), decrease in BPG (5mM), normal temp (37 degrees)
(See slide #8, 12, & 13)
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How is CO2 removed? (3 molecular strategies)
- 1. Major: enzyme catalyzing reaction involving Carbonic Anhydrase
- 2. Minor: hemoglobin amino terminal carbamation
- 3. Least prevalent: Dissolving in blood
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reactants & products of a carbonic anhydrase enzyme catalyzing reaction
- Reactants: H2O(l) & CO2(g)
- Products: H+(aq) protons & HCO3-(aq) bicarbonate
(Note: MUST KNOW HOW TO DRAW STRUCTURES IN REACTION)
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Protons bind to hemoglobin stabilizing __ state, which allows __ oxygen release
T; faster (Acidified conditions causes hemoglobin to release O2 faster)
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reactants & products of an amino terminal carbamation reaction
- Reactants: R-NH2 (R=side chain of an amino acid) & CO2.
- Products: Carbamate (1 H is replaced with CO2) & H+.
(See slide #9. Note: MUST KNOW HOW TO DRAW STRUCTURES IN REACTION)
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Both CO2 major & minor removal strategies lead to the production of __ which __ blood pH
protons (H+); lower
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2 major ways the T (tense) state of hemoglobin is stabilized
- 1. salt bridge formation
- 2. BPG binding
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function of salt bridges in hemoglobin
helps hemoglobin transition from an R (relaxed, oxygenated) to a T (tense, deoxygenated) state. makes the T state stabilized
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How is 2,3-BPG produced?
1,3-BPG mutase isomerizes 1,3-BPG & turns it into 2,3-BPG. (This occurs during glucose breakdown.)
(See slide #11. Note: MUST KNOW HOW TO DRAW 1,3-BPG & 2,3-BPG)
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The binding of the first 3 O2 molecules to hemoglobin is __ & the binding of the last O2 molecule is __
sequential; concerted.
A sequential model allows for the subsequent conformation change to each subunit in a multimeric protein. In a concerted model, a substantial conformational change has already occurred to the protein (minimal conformational change). A concerted transition will have the highest affinity to O2
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When 2,3-BPG binds to hemoglobin, is it a hydrogen bond donor or acceptor?
Acceptor
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