Hemoglobin Flashcards
Myoglobin
a-helical protein with 8 helices and one heme prosthetic group
Hemoglobin
Tetrameric protein with quaternary structure a2ß2
-each a-cahin and ß-chain is bound to a prosthetic heme group
T state of hemoglobin
low affinity for O2
R state of hemoglobin
high affinity for O2
-more O2 bound–> equilibrium favors R state
DeoxyHb
Coordinated by 5 nitrogen atoms
- four from pyrroles
- one from the proximal histidine side chain
Where does O2 bind
distal heme pocket
OxyHb
Fe is hexacoordinate
-five Nitrogens and one Oxygen atom
O2 bond btwn the Fe(II) and histidine E7–> distal histidine
Hemoglobin location and number of O2 binding sites
Contains 4 heme groups
binds 8 atoms of oxygen–> 4 O2 molecules
Myoglobin location and number of O2 binding sites
intracellular transport and temporary storage of O2 needed for aerobic metabolism or muscle
What molecules bind as the 6th ligand and prevent O2 from binding
CO NO H2S cyanide azide sulfide
Mb P50
Much lower then Hb–> higher affinity for O2
Hb P50
cooperative interaction btwn the O2 binding
- high affinity R state
- low affinity T-state
Negative effectors
Stabilize T state
Hb releases O2–> muscles
Positive effectors
Stabilize R state
Hb binds O2–> lungs
[CO2]
In active tissue- low pH–> stabilize T state- carbonic anhydrase increases O2 release
In lungs- CO2 low- protons consumed- high pH–> stabilizes R state- increasing affinity for O2
Carbamylation of Hgb
stabilizes T state–> unloading in capillaries
[BPG]
DeoxyHb bound to BPG displays reduced affinity for O2–> O2 dissociation curve to right
Stabilizes the T state–> binds symmetrically btwn two ß chains in T state
Binding site does not exist in R state
Allows for more O2 release in the capillaries
HbF
beta replaced by gamma
has higher affinity for O2 than maternal Hb
Has lower affinity for BPG
HbS
Glu–> Val @ position 6 of ß-chain
When deoxy–> polymerize into chains
HbC
Glu 6 of ß-chain mutated to lys
Does NOT polymerize like HbS
HbH
ß4 composition
low delivery of O2 to tissues
-binds O2 tightly
HbBarts
Gamma4
High O2 affinity
-poor O2 delivery
a-thalassemia
defect in production of a-chains
-assembly of ß4 or gamma4
HbH in adults
HbBarts in fetus
ß-thalassemia
defect in production of ß-chain
Methemoglobinemia
Heme iron has been oxidized to the ferric state–> does NOT bind O2
cyanosis
Normal blood MET form- maintained by cytochrome b5 reductase
Caused by
- mutations in Hb that stabilize the oxidized form
- defect in the enzyme CYB5R- normally reduces MetHb back to HgB
- Chemical agents such as sodium nitrite
