Oxygen Transporters Flashcards
what is myoglobin? what is the iron surrounded by?
the oxygen transporter of muscle
-4 nitrogens
describe the pocket that heme is tucked away in and why this is helpful
- non polar pocket, sequestered from water
- helps maintain the iron in a +2 state (nonoxidized)
why does oxygen bind more tightly to heme in myoglobin than carbon monoxide?
- steric hinderance
- O2 binds at a 120 degree angle which is preferred, CO binds perpendicularly
what happens to the myoglobin protein when O2 binds? what consequence does this have?
it changes shape (not very much)
-this has little to no consequence because REMEMBER myoglobin is monomer!! (no cooperative binding)
what general shape is myoglobin?
heical
what color is:
- oxygenated myoglobin
- oxidized myoglobin
- deoxygenated
- red
- brown
- blue
what are the roles of the two histidines found in myoglobin?
-one binds the oxygen, the other forms a ligand to the iron which moves when oxygen binds
what constitutes the subunits of Hb?
2 alpha and 2 beta
what is the shape of Hb?
globular
how many heme prosthetic groups does Hb have?
4 heme groups
what does the hill plot show and what does an n>1, =1, and <1 mean?
- this is a chart that shows if there is cooperative binding in a protein
- n>1 = yes, positive coop
- n=0= no cooperativity
- n<1 negative coop
in what range of oxygen pressures does myoglobin work and hemoglobin?
- myoglobin works in low O2 pressures such as muscle
- Hb works best in moderate O2 pressures throughout the body (works over a wider range)
Does the T or the R state of Hb bind oxygen more readily?
R (relaxed?), once one oxygen is bound, Hb moves into the R conformation
-the alpha will change the beta that it is tightly associated with and vice versa
why does the T form exist?
it is more stable in this conformation when not bound to oxygen
why is the T state of Hb more stable?
has more H bonds and electrostatic interactions
-more H bonds between the two ab dimers, specifically
How does CO2 effect the binding of Hb to O?
reduces the affinity for O2, allowing Hb to drop off O2 in tissues that have CO2 accumulating
what does H+ do to the affinity of Hb to O2?
reduces the affinity, allowing Hb to drop off O2 to tissues that have lactic acid accumulated
what is the haldane effect?
deoxygenated blood has a greater capacity to carry CO2 and vice versa
by what mechanism does H+ effect Hb?
it is a negative allosteric regulator ( does not bind to heme itself)
where does CO2 associate with Hb? what is the result of this binding?
the N terminal a-amino groups
-the carbamate stabilizes the deoxy form of Hb relative to the oxy, making CO2 a negative allosteric regulator
does CO2 bind heme?
no
how does BPG interact with on Hb?
binds to the beta subunit in a positively charged cavity
what affect does BPG have on Hb?
lowers its affinity for oxygen
when does BPG rise in the body?
in low oxygen environments (altitude)
what is the fetal form of Hb composed of?
a2gama2
what binds oxygen with a higher affinity, HbA or HbF?
-why?
HbF
-HbF has fewer positive charges in its corresponding pocket than HbA and HbF binds BPG less well
what do the two histidine residues on Hb do?
one forms a ligand to the iron, the other reduces CO binding
what are the three negative allosteric regulators of Hb?
CO2, H+, and BPG
what creates the sickle chape of sickle cell RBC’s?
insoluble HbS
what is the change in amino acid in SS disease and where does this have an effect?
glutamate to a valine on the exterior of the beta subunit
how can sickle cell be diagnosed?
electrophoresis of Hb
-glutame (WT) is negatively charged and valine is neutral
sickling in SC patients is worse in high or low oxygen conditions?
-low, this is due to a hydrohpobic knob being present on the beta subunits of HbS which fits into the hydrophobic hole of alpha subunits of deoxy alpha subunits (this alpha hole is present in WT Hb as well, but not the beta knob)
what were the four treatments of SC discussed in class and their mechanisms?
- antibiotics: prevent secondary infection
- hydroxyurea: stimulates production of HbF which is normal
- BM transplant: replace HbS with HbA
- Gene therapy: works in mice, clinical trials underway
what is methemoglobin?
oxidized form of Hb (Fe3+) and cannot carry oxygen.
what is the clinical presentation of methemoglobin?
shortness of breath, cyanosis, mental status changes
how is methemoglobin diagnosed?
absorption spectrum of the blood
the ingestion of what can promote the formation of HbM?
nitrates and nitrites
what can help treat HbM?
reducing agents (vitamin C and methylene blue)
what is a thalasemia?
an imbalance in the synthesis of the alpha and beta subunits of hemoglobin
what ethnicity are thalasemias common in?
mediterranean, some south asian
what is the treatment for thalassemias?
blood transfusion
a mutation in what subunit of Hb causes SC?
beta
