Hemoglobin Flashcards
Where is myoglobin found
found in muscle for oxygen storage
Single ferous _____- containng heme prosthetic group in protective hydrophobic pocket binds oxygen
Fe++
If oxidized to ferric (Fe+++)
it binds H20
what is myoglobins conformation stabilized by
hydrophobic interactions
Posterior 93 His (proximal) binds:
Fe++
Distal His provides ___ ____ for unfavorable interactions
steric hindrance (CO)
What is a heme
4 pyrrole ring structures linked by methene bridges= porphyrin ring
When you add specific side groups to a heme its called:
protophorphyrin IX
A heme is not considered a heme until you add
Fe++ = heme
Where is heme found
oxygen transporter, and storage proteins and cytochromes
Myoglobin has ____ alpha helical conformation
75% (8 regions)
Myoglobins saturation curve is ____ and is indicative of its function.
hyperbolic; store oxygen until its critically needed
Hematopoietic stem cell directed to erythroid lineage by the hormone
erythropoietin
Hemoglobin relies on ___ and ___ for energy
glucose and glycolysis
Small ___shape allows passage through capillaries
concave
Hemoglobin is found in ____ for ____ transport.
RBC’s; oxygen
Hemoglobin is a tetramer that has 2 ___chains and 2 ___chains. Thus Hb has a quaternary structure and exhibits _____
alpha; beta; cooperativity
What are the similarities between Mb and Hb
- Each has 8 alpha helical regions connected by beta turns.
- Heme prosthetic group
- Distal and proximal histidines
Hemoglobin is designed to deliver oxygen :
all the time; therefore it has a sigmoidal curve
Myoglobin delivers oxygen only when partial pressure of oxygen is:
low; only delivers when need; therefore the curve is hyperbolic
What is the embryonic Hb like
zeta and epsilon chains
What is fetal Hb like
Adult alpha and fetal Beta like (gamma) are expressed during the 2nd and 3rd trimesters.
What is the adult hemoglobin like
2 alpha 2 beta (after 3 months of birth)
Hb conformation and oxygen affinity are dependent on 4 environmental variables:
- pO2
- pCO2
- pH
- 2,3 bisphospho-glycerate concentration
What is the Bohr effect
High [H] (low pH), high pC02, and high [2,3 BPG] lower oxygen affinity and shift oxygen saturation curve to the RIGHT –> Enhances delivery of oxygen to metabolically active tissues where C02 and H+ are accumulating
High ____ levels such as those in lung capillaries favors oxygen binding and shifts oxygen saturation curve to the ____
pO2 ; left
What is CADET, face RIGHT
O2 saturation curve shift to the right and inc O2 delivery in response to increases in:
- CO2
- Acid
- 2, 3 BPG
- Exercise
- Temperature
Acidic conditions favor ___ ____ between chains to stabilize the deoxy or ___ form of hemoglobin. Oxygenation breaks these bonds, and converts the tetramer to the oxy or relaxed (R) form.
salt bridges; T.
___ serves as an acid sensor. Once protonated, it can participate in ionic bonds.
Histidine
When heme ____binds oxygen, the ___moves into the plane of the heme group and ulimately causes conformational shifts that break the ionic bonds (salt bridges) and destabilize the ___ form of Hb.
Fe ++; Fe++; deoxy
Salt bridge formation favors _____
deoxygenation (Oxygen release)
Salt bridge disruption favors ___
oxygenation (oxygen binding)
Not all CO2 binds to Hb; most is converted to :
bicarbonate ion by carbonic anhydrase
Lungs have a high ____ and drive ___on, whereas they have a low ____ and drive ___off
pO2; oxygen
pC02; CO2
Tissues have a high ____ and drive ____. Whereas they have a low _____ and drive ___ off
pCO2; CO2
pO2, O2
What is the chloride shift
Each time bicarbonate enters or leaves a RBC, Cl- is pumped in or out in the opposite direction to maintain charge neutrality.
BPG interacts with ____charges on ___chain amino termini and stabilizes deoxy Hb.
postive; beta
Where do we get 2, 3 BPG?
its a by product of glycolysis; bisphosphoglycerate synthase which is a bifunctional enzyme; feedback inhibited by its end product, 2, 3 BPG
When is there an increase of 2, 3 BPG
during alkalosis and hypoxia
As you increase altitude, pO2 drops which increases ____ to inc production of RBC’s and there is also an inc in ____
EPO, 2, 3 BPG
We’re almost ____saturated at sea level
100%
Salt bridges stabilize ___which delivers oxygen
deoxyhemoglobin
Anything decreases oxygen affinity shifts oxygen saturation curve to the:
right
Fetal hemoglobin (Hb F) has a higher Oxygen affinity than adult HbA and a slightly diff aa sequence in the region for BPG binding which ____the affinity for 2, 3 BPG which shifts the curve to the
lowers; LEFT
In Adult hemoglobin (HbA) BPG interacts with positive charges on ___chain amino termini
beta
In fetal hemoglobin (HbF), it acetylates the ___chain so it cant interact with 2,3 BPG and increases oxygen affinity
gamma
Abnormal hemoglobin refers to sickle cell hemoglobin; There is a glutamate to ____substitution on the beta chain
valine; which causes hyprophib “sticky spot” on Hb tetramer
deoxy HbS tetramers form ___ that precipate in the ___ which deforms cell membrane
fibers; RBC
Sickled RBC are fragile with short half life but this property accelerates destruction of ___infected RBS
malaria
What is Methemoglobin
an abnormal hemoglobin which occurs when iron in ferrous state (Fe ++) is oxidized to ferric state (Fe+++) and there is insuffucient methemoglobin reductase to reverse this.
Ferric state of iron (Fe+++) no longer binds ____ which causes ____
oxygen; cyanosis
Which drugs can induce HbM? Which drugs can reduce it back to the ferrous state (Fe++)
procaine; used in dentistry
reducing agents such as ascorbic acid or methylene blue
HbM can also be congenital due to substitution of proximal Histidine with _____
tyrosine; only heterozygotes survive
What is HbA1c (Glycosolated hemoglobin)
Used as a measure of diabetic control bc glucose in bloodstream will not enzymatically stick to proteins. Hb is in bloodstream so it becomes glycated. It gives the doctor a long term pic of how well their paitient has been controlling their blood glucose levels.
What is carbon monoxide Hb
Carbon monoxide binds more avidly to heme Fe++ than oxygen. Once bound, CO inc O2 affinity of remaining tetramer subunits so less O2 is delivered to tissues.
How do you treat CO poisoning
put in oxygen chamber with 100% O2 to force replacement. You can die if reach >60% COHb
What are the 5 hemoglobin variants
- HbF (fetal hb0
- HbM (Methemoglobin)
- HbS (Sickle cell hemoglobin)
- HbA1c (Glycosylated Hb)
- COHb (Carbon monoxide Hb)
