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8/23 Protein Structure 4; Hemoglobin
Jourd'Heuil4 Theme1
21
Biology
Graduate
08/23/2011

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Term
Hemoglobin is found in?
Definition
Protein in RBC binds O2 from Lungs and transport to tissue
Term
Myoglobin is found in?
Definition
Muscle selves, stores reserve supply of oxygen in time of increase activity
Term
Partial Pressure, arterial and venous
Definition
Concentration of O2, in mm Hg
Arterial 90 mm HG
Venous 40 mm HG
Term
P50
Definition
the PO2 where 50% of the protein is saturated, lower PO2 shows higher affinity
Term
Myglobin dissociation curve
Definition
Hyperbolic affinity too high for venous function
Term
Hemoglobin Curve
Definition
Pure Hemoglobin is similar to Myoglobin
Hemoglobin with BPG is sigmoidal

Curve is result of co-operative behaviour, oxygen binding inreases affinity for future binding
Term
R state
Definition
Oxy state, high binding affinity
Term
T state
Definition
Low binding affinity (release of one O2 decreases by as much as 100x)
Term
How does binging of O2 cause increased affinity in other subunits?
Definition
1) Oxygen changes the position of Iron in porphyrin, binding causes change to R state. Binding oxygen causes iron atom to shrink in size. Attached histine pulls F-helix of beta subunit. Beta2 subunit causes change in alpha1 subunit via electrostatitc interactions. Symmetry of molecule insures that change happen in other half too.
Term
Heme group
Definition
Site of O2 binding; Fe2 is ferrous binds O2 FERROCIOUSLY BINDS o2
Term
Methmoglobin Reductase
Definition

Reduces ferric(+2) hemoglobin to ferrous (+3) hemoflobin, overwhelming the function of or underfunctioning methmoglobin causes related anemia Treat with reducing molecule like methylene blue

(ferrous binds O2)

Term
2.3 BPG
Definition
Biphosphoglycerate, helps stabilize t state by binding to positive residues of the beta subunits (sits in pocket between the two subunits)
Term
F8 v E7
Definition
Distal v Proximal. Distal E7 stabilizes O2 and iron bonding. Proximal F8 causes change in F-helix
Term
CO
Definition
200x more affinity for hemoglobin than O2. Locks into R state. Wont release O2.
Term
Increased in BPG caused by?
Definition
High Altitude
Airway obstruction
Congestive heart failure
Term
Fetal Hemoglobin
Definition
HbF (A2/G2) has low BPG affinity so higher O2 affinity, allows it to snatch up the moms O2 better. Gamma subunits have serines instead of positive His residues.
Term
Low pH
Definition
Co2 and Hydrogen cause a rightward shift, stimulate O2 release via bohr effect
Term
Bohr effect happens because
Definition
salt bridges between His 146 and Asp 94 residues occurs when H is protonated, stabilizing the T-state. Increased H (low pH) stabilizes T state by causing salt bridge formation
Term
CO2
Definition
Donates Protons (right shift)
Co2 reacts with N-terminal to create caramino group which stabilizes t-state by creating e-static ineraction betwen ab dimers.
Term
Sickle Cell
Definition

Change of A6 from glutamic acid to valine in beta hemoglobin. Referred to as HbS causes aggregation of Hemoglobin S intofribril due to hydrophobic pocket. Eventually leads to hemolysis.

Chromosome 11

Term
Thalassemias
Definition
Abnormal Hemoglobin synthesis. Alpha thalasemias have to do with deficiency in a globin subunit and B for beta subunit. High frequency among people near the mediterranean.
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