B4-024 Myoglobin and Hemoglobin in Medicine Flashcards
what is myoglobins quaternary structure?
monomer
what is hemoglobins quaternary structure?
tetramer
myoglobin and hemoglobin moonlight in the conversion of
nitric oxide to nitrate
prosthetic group shared by both
heme
why does the heme prosthetic group need to be bound to proteins?
2 reasons
- free heme binds CO more tightly than O2
- O2 oxidizes the iron in free heme
the observed binding curve of hemoglobin is sigmoidal, indicating
cooperativity and multiple binding sites
RBCs have a high concentration of […] allowing for the binding of many hemoglobin molecules
BPG
excess BPG shifts the equilibrium to
deoxyHb
excess O2 shifts the equilibirum to
OxyHb
BPG preferentially binds to
deoxyHb
the Bohr effect
as pH decreases O2 affinity lowers
excess H+ and CO2 signal tissues need more oxygen
H+ ions […] O2 binding
weaken
Co2 […] O2 affinity
lowers
CO2 binds covalently and reversibly at
N terminal amines
without BPG, what happens to Hb curve?
cooperativity is lost
BPG is upregulated with
hypoxia
BPG is lost during the
shelf life of blood
how does increased BPG affect the binding curve?
shifts right
- decreased affinity
- allows oxygen to release more readily to tissues
BPG does not bind well to fetal hemoglobin, What’s the benefit of this?
- increased affinity for O2
- easier for fetus to get oxygen
how do high altitudes alter binding affinity?
decreased
curve shifts to right
some OTC topical anesthetics oxidize
Fe2+ to Fe3+
cannot bind oxygen, maybe cause of SIDS
effects of metheoglobinemia on binding curve?
cannot reach saturation
- limits oxygen able to carry
- doesn’t affect midpoint
antidote for methemoglobinemia
methylene blue
CO has an [….] affinity for heme
extremely high
substoichiometric effects of CO on Hb
1 CO molecule takes up 1 binding site and increases affinity for O2
- can’t carry as much O2
- can’t release O2
loss of a Hb subunit, results in aggregation of abnormal proteins and anemia
thalassemia
How does Hb Kansas affect the binding curve?
- decreased cooperativity
- decreased affinity
- shifts midpoint right
this hemoglobinopathy results in an unstable protein that dissociates, reducing the amount of Hb available for transport
Hb Kansas
mutation causing Hb Kansas
beta Asn102Thr
free Hb can cause extreme vasocontriction via
consumption of NO converting it to nitrate
dimerization of free Hb causes
kidney damage
oxidation of free heme causes
increased ROS
- synthetic Hb from cross-linked human Hb
- trialed in trauma setting
- raised ethical concerns
polyheme
- synthetic Hb made from cow Hb
- KUMC used this successfully to treat Jehova’s witness
hemopure
normal adult Hb is composed of
2 alpha
2 beta subunits
oxygenated Hb has a […] affinity for O2
high
deoxygenated Hb has a […] affinity for O2
low
promotes release/unloading
the protein component of Hb acts as a buffer for
H+ ions
myoglobin has a […] affinity for oxygen than Hb
higher
myoglobin is composed of
a single polypeptide chain with one heme group
Hb substitutes need to reduce the […] that leads to a blood pressure spike
NO di-oxygenation reaction
decrease affinity for NO, increase Kd for NO
the relationship between Kd and affinity is
inverse
reduced affinity shifts the curve
right
increased affinity shifts the curve
left
BPG allosterically […] the affinity of Hb for O2
lowers
proton binding […] the affinity and [….] pH
lowers
lowers
what causes methemoglobinemia?
nitrates
oxidize the Hb iron to Fe3+
a left shifted O2 binding curve indicates
increased affinity
allosteric mechanisms for lowering O2 binding affinity
2
- Bohr effect
- CO2 toxicity
BPG preferentially binds the
deoxy Hb
allows more oxygen to tissues
