Lecture 9 & 10 - Hemoglobin I & II Flashcards
Two components necessary for Hb production
Vit. B6 and Iron
Two things necessary for DNA synthesis
Vit. B12 and Folic acid
Lack organelles, biconcave (utilizing spectrin), anucleated.
Mature red blood cells
Explain why the biconcave shape is important for RBCs
Through spectrin, the plasma membrane of RBCs have a high ability to deform. This is important because the diameter of capillaries are often smaller that the diameter of RBCs.
Transferrin f(x)
“Salvage” iron from damaged/lysed blood cells
F(x) of haptiglobin
Salvage Hb and excrete in bilirubin (prevents free heme from causing oxidative stress to the body)
Each hemoglobin chain is comprised of ____ alpha-domains.
8
Acts to bind oxygen in the Hb molecule
Proximal (or “E7”) Histidine
Binds to Iron in Hb molecule
Distal (or “F8”) Histidine
Vast majority of adult hemoglobin
Hemoglobin-Alpha
Small % of adult hemoglobin
Hb-A2
Structure of Hb-A
2 alpha subunits; 2 beta subunits
Structure of Hb-A2
2 alpha subunits; 2 delta subunits
Structure of fetal hemoglobin (Hb-F)
2 alpha subunits; 2 gamma subunits
Number of Fe2+ per Hb subunit.
1 (total of 4 in the complete Hb molecule)
Domains of Hb that form the “pocket” for Fe
EFG
What oxidative state does iron take in Hb?
Fe2+
Binds to oxygen and results in a “barrier” to formation of carboxy-Hb
Distal histidine (E7)
The Bohr Effect promotes oxygen release in tissues by what mechanism?
Allosteric effect of incr. [H+] and incr. [CO2]
Binding of oxygen to Hb is under _____ control.
allosteric
This type of control deals with a molecule binding other than at an enzyme/protein active site to change a conformation.
What is “allosteric?”
Iron exists in the ____ state to prevent generation of free radicals.
2+
What is meant by “Hemoglobin is cooperative?”
The binding of one molecule to a Hb subunit causes a conformational in the other subunits.
Compare/contrast Hb and Mb
What molecules inhibit oxygen binding to Fe2+?
Hydrogen ions 2,3-BPG CO2
What is the mechanism behind the offloading of oxygen as a result of increased hydrogen ion []? (In regard to O2-Hb dissociation curve)
Increased [H+] results in a right shift of the oxygen-Hb dissociation curve; this is due to oxygen having less affinity for Hb in acidic environments (actively metabolizing tissue)
What is the mechanism behind the right shift of the oxygen-Hb dissociation curve in increased [CO2] levels?
Increased CO2 levels are found in actively metabolizing tissues. As a result, increased CO2 produces a rightward shift of Oxygen-Hb curve, which means that the oxygen dissociates (“offloads”) freely from Hb in high [CO2]
This molecule maintains the Hb in the T-state, preventing any binding of Oxygen to Hb
2,3-BPG (allows more oxygen offloading)
3 molecules producing a right shift of the oxygen-Hb dissociation curve
Increased: H+ CO2 2,3-BPG
