51: Hemoglobin Flashcards
Myoglobin & Hemoglobin structures
confirmation of myoglobin and single globin monomer (β) of hemoglobin superimposable
key amino acids CONSERVED in correct place
Myoglobin
8 helices, mostly α-helix
allows reversible binding of O2
Ferrous Ion (Fe2+)
four bonds to nitrogen
one bond to globin protein
one bond free to reversibly bind oxygen
iron ion inside globin protein
Hemoglobin A (HbA)
pair of identical
αβ dimers (α2β2
tetramer)
4 globin monomers, carries 4 O2
extensive interactions b/n the subunits: hydrophobic, ionic, hydrogen bonds
Methemoglobin (metHb)
contains Fe3+ (ferric ion) in porphyrin ring
Fe2+ oxidized to Fe3+ when superoxide released instead of dioxygen
Ferric ion doesn’t bind to O2
Remaining 3 O2 sites don’t release oxygen that is bound
MetHb does not function as O2 carrier
Blue people
Deficient in converting metHb to Hb
Myoglobin curve
hyperbolic curve
Myoglobin has higher affinity for O2 than Hb
Cooperative ligand binding
Binding of one O2 molecule promotes binding of another O2 molecule
First O2 binds with lowest affinity, last O2 binds with highest affinity
O2 binding to heme
Fe ion slightly out of plane of heme ring
Fe atom (ferrous) moves into the plane of the heme when oxygenated
conformational change of Hb (tugging)
αβ dimers
held together with a stronger interaction then dimer pairs to each other
“T” (taut)
deoxyhemoglobin
“R” (relaxed)
oxyhemoglobin
2,3- BPG
negatively charged
negative allosteric effector
promotes formation of T state
allows the formation
of additional salt bridges
between the αβ / αβ dimers
decreases O2 affinity for Hb
Promotes unloading O2
in the tissues
Hexokinase deficiency
Reduced 2,3-BPG levels
Left shift on binding curve
Increased O2 affinity
Pyruvate kinase deficiency
Elevated 2,3-BPG levels
Right shift on binding curve
Decreased O2
affinity
Bohr effect
pH decreases, Hb O2
affinity decreases
aerobic tissues form CO2 when producing ATP
CO2acts as an acid when it dissolves in H2O
CO2 and H+ ions signal a
need for more O2
Carbonic anhydrase
promotes formation of carbonic acid from CO2
Allows formation of additional salt bridges
Stabilizes the taut form of Hb
promotes O2 delivery to tissues
Carbamamino hemoglobin
CO2 react with the amino terminus of the α-chains
formation of additional
salt bridges
promotes O2 delivery to tissues
Where does CO2 and H+ leave Hb, which promote the release of 2,3-BPG, as O2 binds?
Lungs
In the lungs
high O2 atmospheric pressure in the lungs is
sufficient to overcome the T-state
O2 may bind
to Hb forcing out the 2,3-BPG, H+ ions are released
CO2 bound to the N-terminal end of
globin is released.
In the tissues
CO2 and H+ ions bind to Hb, which promote the binding of 2,3-BPG, and
the delivery of O2
decreasing O2affinity in response to the decreased oxygen
tension in tissues
T state favored
CO2 transported in blood as?
HCO3
CarbaminoHb
Dissolved CO2
What is responsible for a significant proportion of acid buffering during CO2 transport?
Hemoglobin
Carbon Monoxide
Free heme will bind to
CO 25,000x more tightly than to O2
CO bonds to Hg 200x
stronger then oxygen
Binding is reversible
Carboxyhemoglobin
person who has 50% of Hb O2 binding
sites occupied by CO is near death (or dead)
cherry red appearance
“cherry red is dead”
Carbon Monoxide Poisoning
Carboxyhemoglobin maintains high oxygen affinity
Use 100% oxygen
under elevated pressure (hyperbaric chamber)
α-chain
same in all Hb’s (after
embryo)
γ-chain
disappears soon after birth (HbF)
δ-chain
found in low amounts in adults (HbA2)
HbA (Adult)
α2β2
~90%
HbF (Fetus)
α2γ2
~1%
HbA2 (Adult)
α2δ2
~2%
HbA1C (Adult)
α2β2-glycated
~5%
What binds to 2,3-BPG less tightly, so it has slightly higher O2 affinity?
Fetal hemoglobin
Persistent HbF
Some adults express α2γ2 at high levels
Benign condition
inducing may be cure for β-thalassemia and
sickle cell
HbA1c levels
useful to monitor blood glucose levels over the previous three months
β-globin glycation
N-terminus glycation
non-enzymatic, spontaneous reaction
Hb –> HbA1c
HbA1c no effect on Hb function
Sickle Cell
Hemoglobin S (HbS)
Glu –> Val at position 6
HbS polymerizes, sickle
block blood flow
Causes tissue hypoxia leading to damage (infarcts)
does not alter
the oxygen carrying
properties of hemoglobin
