Erythrocyte Biochemistry Flashcards
65% of Hb is synthesized before the nucleus is extruded; the remaining 35% is made where?
In the reticulocyte
Hemoglobin is a multi-subunit protein (tetramer) made up of 2 ___________ chains and 2 ___________ chains
There is one heme per subunit which contains a _______ atom. It carries oxygen and is _______________ (hydrophobic or hydrophilic?)
Alpha globin; beta globin
Fe2+/ferrous; hydrophobic
Embryonic hemoglobin contains what various types of globin chains?
Zeta
Epsilon
Alpha
Gamma
[Hb Gower 1, Hb Gower 2, Hb Portland]
Fetal hemoglobin contains what type of globin chains?
HbF (alpha2gamma2)
The majority of adult hemoglobin is alpha2beta2, what is the remainder at approx 3%?
Alpha2delta2
Hbs is present in Sickle Cell Anemia, due to what genetic mutation?
Missense mutation at amino acid position 6 in beta-globin
Glutamic acid –> valine
This causes polymerization of hemoglobin –> sickle shaped RBCs impede circulation –> hemolytic anemia
In terms of oxygen dissociation curves, the Mb curve is _____________ and the Hb curve is ___________
The binding of oxygen is _____________ (reversible or irreversible?)
Hyperbolic; sigmoid
Reversible
The oxygen dissociation curve is primarily influenced by what 3 factors?
2,3-BPG, H+, and CO2
Hb binds O2 in a cooperative fashion, meaning what?
As one O2 binds to one heme, it facilitates the binding of an O2 to another heme
Conformational change in one globin subunit induces a conformational change in another subunit
What effect does increased 2,3-BPG have on the oxygen dissociation curve?
2,3-BPG reduces oxygen affinity, so Hb gives up more O2 to tissues
The pH of actively respiring cells is __________, what effect does this have on the oxygen dissociation curve?
Lower; affinity for Hb for oxygen decreases as the pH decreases, favoring the release of oxygen to tissues
A fetus needs Hb that has a higher affinity for O2 than the mother’s Hb (HbF = a2y2). What accounts for the fact that oxygen will flow from mother to fetus?
HbF does not bind well to 2,3-BPG, therefore it has a higher affinity for O2
_________ readily exchanges electrons; thus it is an ideal catalyst for biological redox reactions
Fe
________ is ferrous iron
_________ is ferric iron
Fe2+
Fe3+
Iron plays a role in _______ in the mitochondria
ETC
Most iron is in ___________, and total body iron is 3-5 g
RBCs
Iron is stored in ___________ (liver) and is regulated by modulating absorption
Ferritin
Dietary iron is typically in __________ form
Ferric (Fe3+)
Ferric iron is reduced to Fe2+ by ____________, then transported into the enterocyte by _________ on the apical surface.
Fe2+is transferred to the basolateral side of the enterocyte and is transported outside the cell to the blood and circulation by ___________, which requires a _______________ to perform this transport.
Fe2+ is then changed to Fe3+ so ___________ can carry it to the bone marrow.
Iron content in the body is regulated by modulating absorption - via __________
Dcytb (duodenal cytochrome b); DMT1
Ferroportin; ferroxidase (hephaestin)
Transferrin
Hepcidin
Transferrin binds iron with __________ affinity and carries it to tissues in a non-toxic form, where it is needed including the bone marrow undergoing _____________
High; erythropoeisis
Transferrin Receptor (TfR) - Mediated Endocytosis
Transfer of iron to ______________ (where heme is made) involves the endosome docking on the mitochondria tranferring iron directly - not through a cytoplasmic transport protein.
______ transports iron out of the endosome
Fe3+ is then reduced to Fe2+ by ______________
Mitochondria
DMT1
ferrireductase
What is the primary cause of hypochromic microcytic anemia?
Iron deficiency
What types of physiologic conditions might cause an iron deficiency?
Insufficient dietary iron
Menstruation
Aspirin abuse
GI tract ulcers
What autosomal recessive condition is defined by organ dysfunction due to iron overload: cirrhosis, arthritis, endocrinopathy, skin pigmentation, cardiomyopathy, and usually manifests in the 6th decade?
Hereditary hemochromatosis
