hemoglobin +hemoglobinopathies Flashcards
Hemoglobin Kempsey
locks hemoglobin in its high oxygen affinity. Reduces oxygen delivery to tissues. His92Tyr
Sickle Cell Disease
Glu6Val. Deoxygenated HBs pol
Heme function
Coordinate oxygen increasing solubility
Methemoglobin
Oxidized hemoglobin
Treat with CO2
Stopped by histidine E7
Dimerization between two methemoglobins and O
Artificial porfirins
Strerically hinder from dimerizing
No antigens
Myoglobin (structure)
Catalytic parts (oxygens) of heme on outside, important parts on inside=protects from rusting
p50
affinity of molecule for gas
- increase, forcing gas to interact with molecule
- pressue where half oxygen molecules bound
Smaller the p50 has higher the affinity
Myoglobin
Hyberbolic dissassoctation curve
Kept together by hydrophobic forces
F8 histidine
holds heme in place-binds iron in place
iron’s 6 bonds
4 to porphyrin rings N’s
1 to oxygen
1 to F8 histidine
E8 histidine
Saves us from CO2 poisoning
myoglobin vs hemoglobin p50
hyperbolic with lower p50
sigmoidal with higher p50
what holds both alpha chains together
Arg 141 with Asp 126 and Lys 127
What causes sinusoidal curve
coopertivity
Idealized hemoglobin vs -0 coopertivty
all or no coopertivity-looks very sinusoidal
looks like myoglobin
Hill coffecient
n=2.8 for hemo
=1 for myo
Coopertivity score
pressure in lungs vs prior
100 to 20
T vs R state favor
R state favored when 4 O’s
-T state 2 O’s pushes to R state
T state favored when no O’s on
-R state 2 O’s pushes to T state
Allostery direction
Inhibition or activation
T vs R state affinintity and why
Higher affinity for Oxygen in R
oxygen stabilizes R state
why is T state more stable
disulfide bridges-more favorable
increase pH which state is better
R state favored, His and Lys move apart due to loss of positive charge on His, can take more oxygen (to stabilize)
decrease pH which state better
T state favored-gives more O2-His146 and Lys 64 closer
Co2 binding
Acidifies blood at carbonic acid
Binds to Arg to transport-T state
Diamox
Acetazolamide inhibits carbonic anhydrase-causes buildup of carbonic acid decreases pH His and Lys closer Gives O2 more readily
NO binding
binds to Fe and Cys 93
Release at deoxygenation- Hb allowed to bind to endothelium-vasodilation and increased blood flow
BPG
extremely negative Only binds to T state Helps deliver oxygen Surronded by postive charges Increase at high altitudes Val, his, his, lys More ready to give up o2
BPG in Hbf and why
no bind
histidine 143 to serine
can’t stabilize T
keep oxygen
allosteric binders for T and R
T=low pH, BPG, CO2
R=high pH, O2
HbA, HbF, HbA2, HbA1c
a2b2, a2g2, a2d2, a2b2glucose
Smoking and Hb
CO2 binds to Hb so baby can’t get it
CO poisoning
Binds well on heme
UNLESS histidine E8 is close to it (bends CO bond)
then O2 would much rather bind cuz can make another bond
CO trx
A lot of O2, oversaturate
glycation to make HbA1c
interacts with bpg-lessens affinity
lock out bpg
Good way of testing for diabetes
Cytob5
Makes methemoglobin (+3) to +2 and can be useful again
cyanide poisoning
treat with methemblobin(bonds much easier to that than Hb)
Malaria
Sickleing triggers WBC to kill malaria plasmodium
Thalassemias
B-alpha aggregate into heinz bodies
A-HbH tetramers form with reduced solubility and lacks allosteric regulation in HbA
heme binding AA
His
CO binding AA
His
Bohr effect AA
His and Asp
NO binding AA
Cys
sickle cell AA
Val
Co2 binding AA
Arg and val
BPG bding AA
Val, his, his, Lys
quaternary structure
Arg, lys asp
Hba gly
Val
HbF vs HbA affinity for BPG
his
Ferrous or ferric
ferrous is the one that binds
p50 term
used to describe oxygen pressure at which Hb or Mb is 50% saturated
Greater p50 in regards to O2 affinity
lower
BPG and OxyHb
does not bind
no positive site
HPFH
Herditary persistence of fetal hemoglobin
