Chapter 15- Hemoglobin Flashcards
_____ stores O2 in the muscles
Myoglobin (Mb)
_____ transports O2 in the blood
Hemoglobin (Hb)
How many units of O2 can Mb store? Hb?
Mb- 1
Hb- 4
Which group does the O2 bind to?
Heme group
How many heme groups does Mb contain? Hb?
Mb- 1
Hb- 4
Heme groups consist of:
- A porphyrin derivative (pyrrole rings linked by methane bridges)
- Centrally bound iron atom (Fe (II))
A heme group is called a ____ _____
prosthetic group
The iron atom in the heme group normally remains in the ____ oxidation state
Fe (II)
Color of deoxyHb? oxyHb?
Dark purplish
Brilliant red
Mb and Hb possess reversible action which means they can
bind O2 and release it.
Lower value of Kd means _____ affinity
higher
Lower value of Ka means _____ affinity
lower
Higher affinity means _____ binding
stronger
Mb-O2 dissociation follows a _____ curve
hyperbolic
Why do muscles need O2?
O2 is used by muscles to form ATP
When is Mb most saturated?
The oxygen concentrations are high (aka the muscle is resting)
O2 binding to Hb follows a _____ curve
sigmoidal
The sigmoidal curve of O2 binding in Hb is indicative of a ____ _____
cooperative process
Mb is ill-suited for the ______ of O2, which means its more suited as an ___ ______ ______
transport
O2 storage protein
How does Hb solve the problem of being able to bind and release O2?
A cooperative transition from low affinity to high-affinity state
Two conformations for Hb
T state- tensed
R state- relaxed
binding of O2 in Hb leads to ______ _____
conformational changes
Binding of O2 is a form of _______ ______
Allosteric Binding
What does allosteric binding mean in terms of O2 binding
The binding of a ligand to one site affects the binding properties of another site on the same protein
The conformational changes of binding sites of Hb make it easier for
O2 to bind
After first O2 binds, affinity _____ _______
Increases 100-fold
In deoxyhemoglobin, Fe 2+ is ____ spin
high
When O2 binds, Fe2+ is ____ spin
low
IF nH= 1
Binding is not cooperative
Mb has an n= ?
1
nH> 1 means
Positive cooperativity (Hb)
nH < 1
Negative cooperativity
What does negative cooperativity mean?
binding of one ligand impedes the binding of others.
What does nH correspond to?
the degree of cooperativity between binding sites
n of Hb=?
2.8
What is n?
the slope of the Hill plot
What is the upper limit of nH? what does it mean in terms of binding?
nH=n, all binding sites bind ligand simultaneously
The affinity of Hb changes as ____ changes
pO2
The hill plot of Hb is
curvilinear
At low pO2, Y~
0
At low pO2, Hb subunits compete ___ for O2 and the Hill plot has a slope of ___
independently, 1
At high pO2, Y~
1
At low pO2, how many O2 have bound to the Hb?
Most likely 0, few have bound 1
At high pO2, how many O2 have bound to the Hb?
at least 3/4 of binding sites are occupied
Which pO2 level has the maximum cooperativity?
intermediate pO2
The slope of the Hill plot at high pO2?
slope =1
The slope of the Hill plot at intermediate pO2?
slope ~3
the differential affinity of Hb for O2 in the lungs and peripheral tissues stems from ______ ____ which are ______ ______
effector molecules, allosteric effectors
Oxygen is a ____ and _____ allosteric effector
positive, homotropic
the other three allosteric effectors of O2
- CO2
- H+
- 2,3 BPG
CO2, H+, and 2,3 BPG are _____ and _____ allosteric effectors which means they promote the _____
Negative, Heterotropic, dissociation of O2
pH in the lungs=_____
pH in tissues = ______
7.6 in the lungs
7.2 in the tissues
The tissues possess a ___ pH and a ____ [CO2]
low, high
The affinity of Hb for O2 is ____ in the tissues which means O2 is ______
decreased, released
The lungs possess a ____ pH and a ____ [CO2]
high, low
The affinity for Hb for O2 is ____ in the lungs which means O2 _____
increased, Binds
Bohr Effect
The effect of pH and [CO2] on Hb binding
The H+ effect states
protonation of HIS146 is responsible for stabilizing the T state
The CO2 effect states
CO2 binds as a carbamate group to the N-term of each subunit which forms additional salt bridges stabilizing the T state
The CO2 effect leads to the production of ____
H+
BPG binds tightly to deoxyHb in a ____ ratio
1:1
BPG stabilizes the ______
T state
BPG inhibits O2 binding on ______ subunits of Hb
all 4
Without BPG little O2 would be _____
released by Hb
Synthesis of BPG increases when exceeding altitudes above _____
4,000m
Increased BPG causes a small difference in _____ and a large difference in _____
O2 binding in the lungs, O2 release in tissues
Newborn babies after birth will synthesize more ____ than ____ subunits
gamma, beta
Fetal Hb has _______ than maternal Hb
greater affinity
How can a fetus extract enough O2 from the mother’s blood?
Fetus synthesizes gamma subunits instead of beta which results in a tetramer with a lower affinity for BPG
Sickle cell anemia (HbS) is caused by a ______ which changed _____ to ____ in the beta chain
single mutation, Glu to Val
The mutation for HbS occurs on the _____ of Hb which creates a ________
surface, Hydrophobic spot
The hydrophobic spot on the HbS will form _____ which distorts RBC shape
Fibrils
How is sickle cell treated?
Hydroxyurea and CRISPR gene editing
How does hydroxyurea partially treat sickle cell anemia?
elevates the expression of fetal gamma subunit
Why is sickle cell anemia not observed until several months after birth?
That is when the fetal gamma subunit mutates into beta S subunit
