(11) Erythrocyte Biochemistry Flashcards
Structure of Hemoglobin:
Tetramer:
2 alpha globin chains
2 beta globin chains
What portion of the hemoglobin has iron atom and carries O2?
Heme
What are the three types of embryonic heme?
Hb Gower 1
Hb Gower 2
Hb Gower Portland
When are embryonic Hb depleted?
after 8 weeks
What hemoglobin type increases in fetal state?
Alpha and gamma
What happens upon birth with hemoglobin?
Increase: Beta, delta
Decrease: gamma
What is the composition of fetal hemoglobin?
Alpha2 GAMMA 2
***Treatment of sickle cell anemia
What is the new approach?
Upregulate HbF
With use of HYDROXYUREA to induce HbF
What is the importance of histidine in hemoglobin?
F8 histidine=Proximal histidine which is bound to HEME
E7 histidine=Distal histidine, binds to iron b/w the heme
Describe the conformational change that occurs with O2 binding
O2 changes the position of iron in the plane of heme
-Pulls down the proximal F8 histidine of Hb and changes the interaction with associated globin chain
Oxygen Dissociation Curves:
Hyperbolic curve for ______
myoglobin
Oxygen Dissociation Curves:
Sigmoidal curve for _______
hemoglobin
Oxygen Dissociation Curves:
What is the pO2 (torr) value measuring?
Percent Oxygen binding
Describe positive cooperativity binding with Hb and O2:
Binding of one molecule of O2 to one heme facilitates the binding of an O2 to another heme
Oxygen Dissociation Curve: Modulation by pH (BOHR EFFECT)
Drop of pH from 7.4 to 7.2
Causes a release of O2
*pH of actively respiring tissues is lower
Oxygen Dissociation Curve: Modulation by pH (BOHR EFFECT)
What is the percent change for myoglobin vs hemoglobin in tissues vs lungs?
Myoglobin: 7%
Hemoglobin: 66%
Modulation by 2,3-BPG
What happens with more 2,3-BPG?
Reduces affinity of O2 to allow to give up in tissues
Modulation by exercise:
Drop in pO2 from 40 to 20 torr in __________ tissues corresponds to the steepest part of the oxygen binding curve
exercising
Modulation by exercise:
Hb is very effective in providing oxygen to _______ tissues
exercising
HbF ________ bind well to 2,3-BPG
does NOT
What organ plays a key role in regulating the iron cycle?
LIVER
Distribution of Iron in Humans:
What percentage of iron is in storage form? What are the forms iron is stored in?
27%
Ferritin- H20 Soluble
Hemosiderin - H20 insoluble
Hereditary Hemochromatosis:
Clinical definition?
-TOO MUCH IRON
Organ dysfunction due to iron overload;
15g of total body iron
What is hepcidin?
Regulator of iron homeostasis:
Binding of hepcidin to ferroportin causes internalization of ferroportin
Ferroportin destroyed by proteolysis
RBC production is dependent on _______ and _______
Vitamin B12, Folate
Deficiency of vitamin B12 and folate can cause a severe anemia called:
Megaloblastic anemia
How does megaloblastic anemia occur?
Due to diminished synthesis of DNA in developing RBC in bone marrow
Megaloblastic macrocytic anemia is characterized by:
LARGE erythrocytes
