Hemoglobin Flashcards
_____is a specialized protein designed to transport oxygen
(O2) from the lungs, a region of high O2 concentration, to peripheral
tissues where oxygen tension is low.
Metabolism in the peripheral
tissues generates _______that are transported back to the
lungs, in part, by hemoglobin
Hemoglobin
CO2 and H+
O2 has _____solubility in plasma (the non-cellular part of blood).
As a consequence, >98% of the O2 that reaches tissues is carried in
___________
very low
red blood cells (RBCs) bound to Hemoglobin.
RBCs contain ______which catalyzes the rapid reversible hydration of CO2 to carbonic acid (H2CO3).
H2CO3 then rapidly and spontaneously
dissociates to bicarbonate (HCO3-) and a H+.
carbonic
anhydrase
_____and, _____especially
are soluble in plasma and RBC cytosol and most of the CO2 made in
tissues returns to the lungs as those species.
About _____of the CO2 made is carried bound to Hb
CO2
HCO3-
14%
What is the structure of hemoglobin?
Hemoglobin is a heterotetrameric protein having the subunit composition (αβ)2. The α and β subunits have similar sequences and tertiary structures.
Both subunits in hemoglobin are evolutionarily related to____, a monomeric protein abundant in muscle that is
designed to store O2.
myoglobin
In hemoglobin what binds O2?
contain a heme prosthethic group that is responsible for binding O2.
What is the form of Fe that can bind O2?
Fe2+ is the ferrous form of iron that is capable of binding O2;
What is the form of Fe that cannot bind O2 and what is it called?
Fe3+ is the ferric form of iron that CANNOT bind O2 and is present in an INACTIVE form of hemoglobin called methemoglobin (metHb)
Describe hemoglobin’s binding curve
what about myoglobin?
Hemoglobin shows sigmoidal cooperative binding of oxygen that is a direct result of its more complex subunit structure.
Myoglobin gives a normal binding curve which is hyperbolic in shape.
the partial pressure of oxygen yielding 50%
saturation of binding is termed ______ this value is analogous to Km for the binding of substrates to enzymes.
the P50;
Why is cooperative binding so important in hemoglobin?
The cooperative binding of oxygen by hemoglobin is critical for its
efficiency in loading oxygen in the lungs and unloading oxygen in the peripheral tissues.
the______
of Hb allows it to release a
much larger fraction of its O2
load at the pO2 levels found in
the blood of working and
even resting muscle
cooperativity
Hemoglobin exhibits sequential cooperativity for oxygen binding. Thus, the binding of oxygen to one subunit induces a ______ that is partially transmitted to adjacent subunits.
conformational change
The transmission of the partial conformational change induces an
increased affinity for oxygen by these adjacent subunits.
R=
T=
R=relaxed=high affinity;
T=taut=low affinity
Why is high amounts of CO a problem for O2 transport?
Carbon monoxide (CO) has ~250-fold higher affinity
for Hb than does O2. When bound to the heme group
of one subunit, it causes all four subunits to “lock” in
the R conformation, thereby limiting oxygen release
in peripheral tissues
How Does O2 Binding Change the Conformation of a Hb Subunit?
Without O2 bound, the heme Fe2+ is pulled away from the plane of the porphyrin ring by a His residue of the Hb polypeptide chain
When O2 binds, it pulls the Fe2+ back into the plane of the ring and that moves the His residue and its whole section of the polypeptide chain. That in turn causes the Hb subunits to shift relative to one another to an arrangement that favors the R-conformation.
An ______ or____ is a molecule that can bind to a protein and induce aconformational change that alters the affinity for substrate (or ligand such as oxygen) at some other site.
allosteric regulator
effector
(H+), CO2, and 2,3-diphosphoglycerate (DPG) ALL can bind to Hb and
reduce its
affinity for O2
–causes LEFT shift
If O2 is high, then the equilibrium is driven to the____ and H+ and
CO2 and DPG will dissociate from Hb as O2 binds
right