CB4 Flashcards
is the heme group part of the polypeptide chain
no
the heme group is ______ bound to the protein
tightly
the heme group is ______ for Hb activity
essential
iron is held in position by 4_____
nitogens
myogloblin I is an _____ resevoir within the heart and skeletal muscles
oxygen
5 structural components of myoglobin 1
structure of myoglobin II
label this schematic
the interior of myoglobin is hydrophobic except histidines __ and __
E7, F8
in deoxy-mb, the heme iron lies _____ angstrom out of the plane. in oxy-mb, the heme iron lies ___ angstrom out of the plane.
0.3, 0.1
mb has a ______ affinity for oxygen than Hb, but once Hb has gotten 3 oxygen atoms it has ______ amt of affinity for oxygen as Mb
larger, about the same
just read it. when oxygen binds to the heme group, that is what causes the His F8. The movement of His F8, on the Helix F, then causes the other elements of the structure to move. This is when the structure goes from nonplanar to planar. true or false
true
Mb is a _____ protein
storage
Mb binds O2 ______, and dissociates ______
avidly, slowly
Mb is/isn’t cooperative
isn’t
Mb has ______ polpeptide chain(s)
one
the 2 main functions of Hb is to transport ____ to tissues and transport ___ and ____ away from tissues
O2, CO2, protons
Hb has _____ polypeptide chain(s) and each chain has a heme group. this means that each Hb can bond ______ oxygens.
4, 4
the subunits on Hb are held together by ________ interactions
non-covalent
HbA is a _______ protein. (quarternary structure of 4 subunits)
tetrameric
the four subunits of HbA are ____
alpha2beta2
on HbA, an alpha chain is _____ aa’s long and a beta chain is ___ aa’s long
141, 146
HbA predominates in appx. ____% of adults, whereas a reduced number of adults express _____
85, HbA2
fill in the chart
_________ reflects the amt of oxygen gas dissolved in the blood
the PO2 (partial pressure of oxygen)
the saturation curve for O2 binding to Hb is _______, which is indicative of _________ binding
sigmoidal, co-operative
Hb dissociates at a _____ partial pressure than Mb. This allows delivery of O2 from _____ to _____.
higher, Hb, Mb
the fact that the O2 dissociation curve for Hb is sigmoidal means that the _______ are all working together.
protein subunits
Fill in the chart:
in fetuses, O2 flows from maternal _______ to fetal _________
deoxyhemoglobin
in Hb, the affinity of the 4th O2 bound is ________ greater than the 1st O2 bound
300x
T-form Hb has a _____ affinity for O2 compared to R-form Hb.
lower
globular proteins form ______ in water
colloids
explain t and r states in terms of dimers
At first, deoxy Hb has a low affinity for oxygen because it is in its T state. While it is in T-state, all the alpha and beta dimers are held tightly together through ionic bonds and hydrophobic interactions. once 1 O2 molecule gets in, the Hb tends to relax a little, and its affinity for more O2 molecules increases. It turns from tense to relaxed (R-state). Once all 4 of the O2 molecules are attached to the Hb, it turns from deoxy-Hb to oxy-Hb.
What are the 3 allosteric effects on Hb?
heme-heme interactions/cooperativity, the Bohr effect, and 2,3-BPG
Describe WHAT CAUSES the signmoidal curve of the oxygen dissociation graph of Hb.
when O2 binds to 1 heme group, specific structural changes occur. these changes are then transmitted to other heme groups within the Hb tetramer.
The O2 dissassociation curve for Hb shows us that Hb can carry O2 more efficiently from places of high O2 pressures to low O2 pressures. This effect is called ______ which allows Hb to deliver a high amt of O2 to tissues in relatively low Partial pressures of O2.
cooperativity
The Bohr effect is when the RELEASE of O2 from Hb is increased in the presence of _______ CO2 levels and ______ pH levels.
increased, low
The Bohr Effect:
A low pH and a high conc. of CO2 results in _____ O2 affinity for Hb. There is a shift to the _____ on the O2 dissociation curve. This stabilizes the ______ state.
decreases, right, T
2,3-BPG is the regulator for the binding of oxygen to ______
Hb
what would happen to the oxygen dissociation curve if CO2 levels where decreased and if the pH was increased? What state does it stabilize?
It would shift to the left, R state
2,3-BPG decreases oxygen affinity of Hb by binding to ________, but not ________. This binding stabilizes the _____ state.
deoxyHb, oxyHb, T
2,3-BPG forms _______ with positively charged aa’s on the ____ subunits in a central cavity. These salt bridges need to be ________ during oxygenation, so the cavity narrows and squeezes the 2,3-BPG out.
salt bridges, beta, broken
Hb from which 2,3-BPG has been removed has a ______ oxygen affinity.
high
what is P50 when Deoxy-Hb + 2,3-BPG is present? what is P50 when Deoxy-Hb is alone?
26 torr, 1 torr
in the absense of 2,3-BPG, oxygen affinity is ____
high
2,3-BPG shifts the O2 dissociation curve to the ____
right
at low [O2], 2,3-BPG = more or less O2 DELIVERY to tissues
more, because 2,3-BPG increases the RELEASE of O2
for people who have hypoxia, are at high altitudes, or chronic anemia, 2,3-BPG increases or decreases
increases
what does CADET, face Right mean?
CO2, Acid, 2,3-D(B)PG, Exercise, and Temperature are all physiological states that inc. tissue requirement for oxygen, which means that it pushes the oxygen dissociation curve to the Right
__% of erythrocytes are destroyed per day
1
anaemia is a decrease in ___ concentration below the reference range for the age and sex. Give the ranges and respective sexes.
Hb,
- 5 – 16.0 g/dL (female)
- 5 – 17.5 g/dL (male)
Inherited haemolytic anaemia, also called _________, is where the body has a ______ deficiency.
sickle cell anaemia, GP6D
Sickle-cell anemia is caused by a point mutation in the _____-globin chain of hemoglobin. It replaces the amino acid _______with the less polar amino acid ______ at the sixth position of the β chain.
beta, glutamate, valine
The valine in sickle cell anemia is exposed on the surface which forms a ____ patch in low O2 conditions
sticky
Effects of sickle cell anemia:
- there are ________ interactions between HbS subunits.
- It leads to the stacking of ______ into long fibers at _____ O2 levels.
- Fibers distort the erythrocyte into _______ cells.
- Capillaries experiences _______.
- Tissues get ______, which causes pain and cell death near blockage.
- Sickling gives rise to ________, ______, _____, or _______
- hydrophobic, 2. HbS and low, 3. sickle, 4. blockage, 5. anoxia, 6. dehydration, cold, hypoxia, infection
what is the process of fiber growth in erythrocytes when someone has sickle cell anemia?
nucleation, growth, and alignment
What are the 4 main clinical consequences of sickle cell anemia?
bone pain, chronic anemia, organ damage, cerebrovascular accidents
What 2 things could be required for the diagnosis of sickle cell anemia?
protein analysis or DNA analysis
What are some of the options for treatment of sickle cell anemia? (6)
Treat the symptoms, hydration, analgesics, aggressive antibiotics, blood transfusion, and hydrxyurea (which raises HbF levels)
Hydroxyurea is traditionally a(n) ________ drug
anticancer
hydroxyurea changes _________ expression levels
gene
hydroxyurea ________ HbF levels
increases
Usually, HbF is/isn’t expressed in adults
isn’t
HbF levels can be measured in the patient’s ______
blood
G6PD deficiency is the most common enzyme abnormality, affecting ________ people globally.
over 200 million
A G6PD deficiency is most prevalent in the ______, _____, _____, and ____
Mediterranean, middle east, tropical africa, and asia
G6PD is an ______, ___-linked gene
inherited, X
There are more than _____ mutations of G6PD, but only some mutations can cause ______.
400, symptoms
NADPH minimizes the damaging effects of ________.
Reactive Oxygen Species (ROS)
ROS are produced as a by-product of ______ metabolism. ex. ______
aerobic, Hydrogen peroxide (H2O2)
ROS impose ________ on cells by attacking DNA, proteins, and lipids.
oxidative stress
oxidative stress can lead to ____-
cell death
______and ______ convert ROS into o2 and h2o
SOD and catalase
________ detoxifies H2O2 using __________ (2G-SH), which is converted to the oxidized form (_-_-_-_)
glutathione peroxidase, glutathione, G-S-S-G
Know this diagram:
The presence of Heinz bodies represents _______ to hemoglobin and is classically observed in _______ deficiency.
oxidative damage, G6PD
Mechanism of G6PD deficiency: ROS damage to membranes = _____ cleared more rapidly
erythrocytes
Factors increasing _________ lead to hemolytic anemia
oxidative stress
Oxidant drugs (3)
antibiotics, antimalarials, antipyretics
what is favism
ingestion of fava bean
the most common precipitating factor of a G6PD deficiency is an _______. this induces a _________.
infection, inflammatory response
During an inflammatory response, free radicals are generated. What are free radicals?
free radicals are a molecular trigger that starts inflammation.
neonatal _____ is also a precipitating factor of a G6PD deficiency.
jaundice
the 2 possible symptoms of neonatal jaundice is impaired ______ of heme or an increased production of _______
catabolism, billirubin
