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41 Cards in this Set

  • Front
  • Back
In which state do hemoglobin bind oxygen, T or R state?
R state
What do the following cause a shift to, R or T state? (a) Hb binding H+, (b) Hb binding CO2, (c) high [3-BPG]
(a) Hb binding H+: T state, (b) Hb binding CO2: T state, (c) high [3-BPG] R state
What is the Bohr effect with respect to O2 binding to Hb?
It is the effect that protons (or pH) has on Hb binding O2 (or the effect that pH has on the slope of the O2 satruation curve)
What effect does pH have on T or R state? (hint: think of pH as influencing the slope of the saturation curve, where low pH has a steeper curve.)
Low pH favors T state, high pH favors R state
What is P50 mean in terms of PO2 (oxygen partial pressure)?
P50 means the oxygen partial pressure at 50% saturation.
What effect does lowering the pH have on P50?
It increases the P50, thus at lower pH there will 50% saturation at higher PO2... in other words heme will release O2 at low pH
Given that at lower pH there will 50% saturation at higher PO2, at low pH will Hb favor binding or releasing O2?
releasing O2, thus at low pH the T state is favored
What effect does increasing P50 value have on O2 binding?
Increasing the P50 value means less O2 binding at a given pO2
will high pH favor Hb binding of O2 at lower [O2]
Yes, high pH means that the Hb is going to be more likely to bind O2 at low [O2]
What effect does an increase in P50 have on Hb binding to O2?
increasing the P50 means that Hb will bind less O2 at higher partial pressure.
What does high [CO2] have on the P50 value?
High [CO2] increase the P50 value, thus high [CO2] concentration means less O2 binding by Hb
What is carbamate formed by?
the binding of CO2 to Hb
Does carbamate favor the T or the R state?
the T state
In which direction does [CO2] shift the saturation curve?
to the right, thus there is less Hb O2 binding when [CO2] is high.
What effect does a high [2,3-BPG] have on P50?
P50 increases as [2,3-BPG] increases… thus they are proportional.
So, what effect does high [2,3-BPG] have on Hb binding oxygen?
high [2,3-BPG] inhibits O2 binding to Hb
How does having plenty of 2,3-BPG in RBCs support the function of RBCs in the transport of oxygen?
If not for 2,3-BPG, Hb would only be able to release oxygen at very low pO2 (or Hb would behave more like Mb if not for 2,3-BPG)
Can [2,3-BPG] effect P50 and in doing so regulate O2 binding to Hb in RBCs?
yes
Which of the following favor the T and which favor the R state of Hb? (a) High [H+], (b) High [2,3-BPG], (c) High [CO2], (d) low temperature
(a) High [H+]: T, (b) High [2,3-BPG]: T, (c) High [CO2]: T, (d) low temperature: R… thus environmental changes in all these, or an increase in all these results in the release of O2 from Hb.
Does gamma-Hb have a greater or lesser affinity for 2,3-BPG? What effect does this have on the binding of O2 to gamma-Hb (in the fetus) versus ∂-Hb in mom?
(a) Gamma-Hb has greater 2,3-BPG affinity, (b) Gamma-Hb behaves more like muscle and binds O2 at lower O2 concentration, thus O2 will move across the placenta toward the fetus… so gamma-Hb has a lower P50 value than ∂-Hb.
Which has a lower P50 value, gamma-Hb or ∂-Hb?
Gamma-Hb
Which of mom's Hb has a lower P50, a smoking or non-smoking? What effect does this have on the fetus?
(a) Smoking Mom has a lower P50, which means it binds O2 better, (b) the fetus of the smoking mom will have less O2 flow across the placenta (something called the diffusive gradient)
What type of diffusive gradient do we want between the mother and the fetus? What happens to the diffusive gradient in mothers that smoke?
Large… small
In what state does the heme bind more oxygen, when the iron is in the ferrous state (Fe2+) or ferric state (Fe3+)?
Fe2+ ferrous state binds oxygen
What does ferro-Hb (HbA) mean and what does ferri-Hb (met-heme) indicate in terms of the reduced state of the iron?
(a) HbA (ferro): Fe2+ or oxygen binding is better. (b) met-hem: Fe3+ or oxygen binding is less than HbA,
what is the amino acid difference between HbA and met-heme?
(a) HbA: has a histidine in the ß-chain, (b) met-heme has a tyrosine in the ß-chain.
Is it normal for Fe to become oxidized from Fe2+ to Fe3+?
yes
(a) Which enzyme and (b) reducing equivalents play a role in returning the iron in Hb back to its reduced state of Fe2+? (c) show the flow of electrons.
cytochrome B5 reductase, NADH and cytochrome B3 (electrons go from NADH -> cytochrome B5 -> Hb)
What would a deficiency in cytochrome B5 cause?
Hemoglobin would remain in the met-Hb state… patient would be cyanotic due to ineffect oxygen transport of RBCs
What is the benefit of going from a ferrous state to a ferris state?
reduces the amount of reactive oxygen species (ROS) in the cell, less cell damage.
Why does would a person with a deficiency in G6P, that had an oxidative stress situation, where ROS where being produced, be likely to become cyanotic?
NADPH is oxidized by G6P as part of the pathway associated with glutathione, also G6P is reduced and enters the PPP, then to glycolysis to produce NADH which is need as a reducing agent in the cytochrome B5/HbA pathway.
What effect does NO have on microvasulature?
dilation
Where does the NO come from in the dilation of microvasulature?
It comes from NO-Hb
Where does NO bind on Hb?
it comes from -Sh of ß-Cys-93
Would deoxy state (T), favor NO binding?
No… oxy state (R) would favor binding of NO... in other words, you want NO bound when O2 is plentiful (R-state) and released when oxygen is scarece (T-state)
What is the positive consequence for release of NO under low [O2]?
Low [O2] -> NO is released -> vasodilation
In RBCs, what is the use for the NADH produced in glycolysis? What advantage does this give the RBC in terms of glycolysis?
(a) cytochrome B5 is reduced, met-Hb is reduced, (b) restores NADH to NAD+
What percentage of CO2 is transported as carbamino-Hb? How readily is the CO2 released from this form?
(a)Ten percent, (b) the reaction is readily reversible, so no enzyme is required.
What effect does increased [CO2] have on blood pH? What effect does this change in pH have on Hb affinity for oxygen?
(a) High [CO2] lowers blood pH, (b) low blood pH causes a lessened affinity of Hb for O2.
In what form is most CO2 transported?
bicarbonate (HCO3)
In isohydric transport of CO2, (a) what happens to CO2 upon entering an RBC in the tissues? (hint: H2O + CO2)… (b) What happens in the lungs?
(a) In the presence of carbonic anhydrase, H2O +CO2 -> H2CO3… then H2CO3 + HbO2 -> HCO3 + H+Hb + O2… the H+ causes the dissociation of O2, which then diffuses to the tissues, HCO3 exits the cell and transported in the plasma to the lungs. (b) This process is reversed int the lungs, because O2 diffuses into the cell. HCO3 diffuses into the RBC and collects the dissociated H+, due to a concentration gradient.