Hemoglobin and Myoglobin Flashcards
Hemeprotein
proteins with heme as tightly bound prosthetic group
Prosthetic Group
coenzyme permanently associated with enzyme or protein
Cytochromes
heme group serves as electron carrier that can be oxidized and reduced
in ETC
Catalase
heme is part of active site of enzyme that catalyzes breakdown of hydrogen peroxide
in peroxisomes
Heme use in Myoglobin and Hemoglobin
heme used to reversibly bind oxygen
Heme Structure
iron in center of porphyrin ring
makes 6 bonds- 4 to iron, 1 to R group of histidine of globin, 1 to oxygen
Myoglobin
in heart and skeletal m
O reservoir; carrier that increases transport rate w/in muscle cells
Hemoglobin
Red Blood Cells
transports 4 O2 mol from lungs to capillaries of tissues
transports CO2 and H from tissues to lungs
T Form
deoxy form when no O bound
low O affinity
R Form
O binding causes break of some polar bonds of T form
high O affinity
O binding myoglobin vs hemoglobin
1 O to Myoglobin
4 O to Hemoglobin
Myoglobin has higher affinity
Bohr Effect
Decreases O affinity at lower pH
shifts curve to right
stabilizes T form
2,3 BPG
stabilizes T form
decreases O affinity
shifts curve right
CO2 Binding
stabilizes T form
less O affinity
shifts curve right
CO Binding
hemoglobin has higher affinity for CO than O; binds more closely
higher O affinity
R form
Shifts curve left
Fetal Hemoglobin
HbF
lower affinity for 2,3 BPG (missing some + aa in beta chains of 2,3 BPG)
higher O affinity
shifts curve left
Stabilizes R form
What are the proton sources that decrease pH so the Bohr effect can take place?
acids made by tissues (lactic acid)
high levels of CO2 at peripheral tissues (carbonic acids and bicarbonate)
pH gradient between lungs and tissues
CO2 releasing carbonic acids and bicarbonate from tissues makes a higher pH in lungs and lower at tissues
hemoglobin becomes more efficient oxygen transporter
Mechanism of the Bohr Effect
Deoxyhemoglobin has a higher affinity for protons than oxyhemoglobin (histidine R groups have higher pKa when not O bound)
become protonated = charged R group
charged group form stronger ionic interactions- lower O affininity
Where does 2,3-BPG effect take place?
high concentrations of RBC
binds only to deoxyhemoglobin- decreases O affinity
Mechanism of 2,3- BPG
binds in pocket between 2 beta globin chains in deoxyhemoglobin chains contain (+) aa that bind (-) 2,3- BPG O binding = BPG removed
Response of 2,3- BPG to anemia/ chronic hypoxia
2,3-BPG levels rise
increases ability to unload O in tissues
Role of 2,3- BPG in transfused blood
needed for normal transport
w/o O can not be unloaded efficiently
BPG lost when blood is stored; O binds too tightly in transfused patients until BPG levels return to normal
Transporting forms of CO2
Normal- bicarbonate ion
Or- carbamate bound to N terminal aa of hemoglobin which forms carbaminohemoglobin
Where does CO2 dissociate from hemoglobin?
Lungs
Affect of CO binding to hemoglobin
tight binding (200x higher affinity) No O can unload at peripheral tissues
Effects of fetal hemoglobin
higher O affinity
able to absorb O from maternal circulation across placenta
Hemoglobin A2
minor hemoglobin with unknown function
Sickle Cell Anemia
Hemoglobin S disease
Glutamate replaced by valine (more +)
RBC lifespan about 20 days
T form stiffens and distorts cell
can interrupt flow through capillaries- anoxia- can kill tissue
Hemoglobin C Disease
Lysine substituted for glutamate
homozygotes have mild chronic hemolytic anemia
Hemoglobin SC Disease
genetics- 1 HbS and 1 HbC
some sickling and crises
