Quiz 7 Flashcards
myoglobin
with its single heme prosthetic group, exhibits a hyperbolic O2 binding curve
hemoglobin can adopt
the deoxyribose (T) or oxy (R) conformation, which differ in O2 binding ability
Hemoglobin (Hb) and myoglobin (Mb)
are oxygen-transport and oxygen-storage proteins
Mb is
monomeric
Hb is
tetrameric
- it is formed by a dimer of a B dimers
Hb has
2 alpha chains of 141 residues, 2 Beta chains of 146 residues
iron interacts with
six ligans in Hb and Mb
four of these are the
N atoms of the heme porphyrin
a fifth ligand
is donated by the imidazole side chain of amino acid residue His F8
His F8
this residue is on the sixth or “F” helix, and it is the 8th residue in the helix
When Mb or Hb bind oxygen,
the O2 molecule, itself, binds to the heme iron, as the sixth ligand.
bound O2 molecule is
tilted relative to a perpendicular line to the heme plane
Fe in Mb is
Fe2+, Fe(II)- ferrous iron- the form that binds oxygen
mb with ferric iron Fe2+ is called
metmyoglobin and does not bind to oxygen
when oxygen bind to Fe2+ in heme of mb,
the heme fe2+ is drawn toward the plane of the porphyrin ring
for Mb, this small change has a little consequence
but a similar change in Hb initiates a series of conformational changes that are transmitted to adjacent subunits: very consequential
Mb, an
oxygen-storage protein, has a greater affinity for oxygen at all oxygen pressures
Hb becomes saturated with
O2 in the lungs, where the partial pressure of pO2 is high about 100 torr
in capillaries pO2 is
low, about 40 torr, and oxygen is released from Hb
the binding of O2 to Hb
is cooperative, binding of oxygen to the first subunit is tough, but it makes binding to the other subunits more favorable: cooperatively
oxygen binding pulls the
Fe2+ into the heme plane
as fe2+ moves,
it drags His F8 and the F helix with it
this change is transmitted to the subunit interfaces, where the conformation changes leads to the
rupture of salt bridges between polypeptide subunits
changes occur at the
4th level, leading to conformational change
Hb must be able to
release oxygen in capillaries
bohr effect
explains the connection between CO2, H+ and conversion oxy-Hb(R) to deoxy-Hb(T)
thus as pH decreases
dissociation of O2 from hemoglobin is enhanced
binding of protons,
H+ diminishes oxygen binding on Hb
as the tissue-capillary interface, CO2 hydration
and glycolysis produces extra H+, promoting addition disassociation of O2 where it is needed most [tissues]
at the lung-artery interface, the reverse reaction,
bicarbonate dehydration [required for CO2 exhalation] consumes extra H+, promoting CO2 release and O2 binding
2,3 -BPG
an allosteric effector of hemoglobin
the sigmoid binding curve, which reflects high sensitivity for O2 binding and release,
is only observed in the presence of 2,3 BPG
since 2,3 BPG binds at a site distant from the F2+ where oxygen binds, it is called an
allosteric effector
in the absence of 2,3 BPG
oxygen binding to Hb would have a hyperbolic curve like Mb
where does 2,3-BPG bind?
- “inside”
- one molecule binds, in the central cavity formed by the four subunits
what is special about 2,3 BPG?
negative charges interact with 8 positive charges in the cavity
fetal Hb(Hb F)
has lower affinity for 2,3-BPG and higher affinity for oxygen, so it can take oxygen from mothers Adult Hb (Hb A)
the ionic binding 2,3 BPG to the two
B subunits of Hb
gas exchange takes place across the
placenta
fetal Hb(Hb F) differs from adult Hb
- with y chains in place of B chains and this an a2y2 structure
Why does fetal Hb (Hb F) bind O2 more tightly than Adult Hb (Hb A)?
- Fetal γ-chains have Ser instead of His at position 143 and thus lack two of the positive charges that stabilize BPG binding.
- As a result, Hb F has a higher affinity for O2
sickle-cell anemia patients
have abnormally shaped red blood cells
the cause is a single amino acid substitution in the
B chains of hb Glucoses at position 6 of the B-chains is replaced by val
as a result, Hb S molecules
aggregate into long, chainlike polymeric structures that poke the erythrocyte membrane into a sickle shape
the polymerization of Hb S molecules arises because
val replaces glu on the surface of B chains
these can insert into
hydrophobic pockets in neighboring deoxy Hb S molecules
