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Flashcards in Hemoglobin Lectures Deck (24):


Fe 2+ is the cofactor
Carries oxygen in blood


Proteins that protect heme from auto-oxidation

Heme is the O2-binding molecule common to myoglobin and hemoglobin
Porphyrin molecule to which an iron atom is coordinated
Once sequestered inside a hydrophobic pocket created by folded globin polypeptide, heme encounters a protective environment that minimizes oxidation of iron in presence of oxygen or interacting with other hemes to oxidize



Partial pressure of oxygen at which half of the protein sites are saturated
Large p50=weaker affinity=wants to let go of the oxygen easier


Measuring oxygen binding

Measure ratio of oxygenated:deoxy blood at 660nm and 940nm (because these exhibit biggest changes in absorbance) to figure out saturation of oxygen in blood
When you oxygenate hemoglobin, there is a change in color/absorbance pattern and that's what you're measuring



Singular chain protein 153 aa
Contains a heme in center
Hyperbolic oxygen dissociation curve
In cytosol of muscle cells
Binds o2 diffused from blood to muscle
Alpha helix E and F hold heme in place, H controls gasses that can bind to heme
Core is all hydrophobic residues



4 subunits, 2 alpha 2 beta
Different globin gene encodes each type of subunit
One heme is located within a hydrophobic pocket in each subunit of Hb. So you've 4 total heme groups


Hb and Mb

Almost no redundancy in code, but when you superimpose 3D structures they look incredibly similar

O2 transport, in RBCs, high amount of O2 bound at PO2 in lungs, low amount in tissues, quaternary structure (tetramer), sigmoidal binding curve (cooperative binding of multiple subunits), 4 heme groups (one/subunit)

O2 storage, in skeletal muscle, high amount of O2 in lungs, high in muscle too, monomer, 1 heme, hyperbolic curve


Forces that hold hemoglobin together

Intra-subunit salt bridges
DKR ionic interactions
Aren't held rigidly in place because you need the subunits to flex and move


Cooperatively and kinetics

First binding has low affinity (energy of substrate-energy of protein) and affinity increases as substrate binds. So binding increases subsequent affinity


Sigmoidal curve of hemoglobin

Is because of cooperativity and multiple O2 binding, NOT a shift in p50. We only look at 2 states: bound and free, but in reality there are many intermediate micro states between bound and free.
Also, affinity is independent of oxygen/hemoglobin concentration. Affinity is an intrinsic property


Hill constant of hemoglobin

In reality: 2.8
Hill constant tells you how well the different subunits talk to each other
N=1, you get a hyperbolic curve (like the one for Mb)
N=4, you get a perfect sigmoidal curve (as for perfect, theoretical Hb)


Enhancing oxygen delivery

Sigmoidal curve allows you to pick up more and deliver more than hyperbolic curve. Hemoglobin doesn't leak oxygen, it delivers in hypoxic environments. Change in saturations is twice as high in Hb as compared to Mb. Much more Hb is saturated at P=100 in lungs b/c of cooperativity


Models of cooperativity

In acidic environment, T state is highly favored. In basic env, R state is highly favored. AB subunits slide past each other and rotate, narrowing b pockets as oxygen binds. Perpendicular in T state to parallel in R state. Hb goes through very small, electronic changes but it increases affinity.


Allosteric Effector

Molecule that exhibits changes in protein function by binding in proteins at sites that are spatially distinct from active site.



Good for treating altitude sickness
Releases bicarbonates in blood so Hb delivery is better


NO binding

Both cooperative and allosteric. Cooperative bc it binds to oxy on active site. Allosteric bc it can also bind to a cys away from as. Getting off with oxygen binds to vascular endothelium and causes vasodilation and increased blood flow



Has lower affinity for 2,3 BPG than HbA. Increased R state and increased oxygen carrying capacity and decreased p50



Has 250x affinity for heme as compared to oxygen. Treated with 100% oxygen or hyperbaric oxygen. CO poisoning produces cherry red discoloration of organs/skin. But His keeps oxygen rather than CO bc of binding interactions



Good test for blood glucose levels. Glycosylating sugars if sugars are too high in the blood.


Treatments for Sickle

Hydroxyurea, butyrate stimulate production of HbF
Bone marrow and stem cell implants are also an option


Alpha thalessimia

1 gene: silent
2: trait
3: disease
4:hydrops fetalis and death bc no alpha chains
B4 tetramers form (HbH) and have reduced solubility and lacks allosteric regulation


B thalassemia

Heinz bodies: alpha chains aggregating and precipitating
Not affected until after birth
Major: healthy until age 2 and then anemia
Bone marrow replacement can cure



Genetic disorder of Hb synthesis
Gene is missing
Gene present but expression is impaired
MRNA produced but encodes defective Hb
Major: homozygous defect
Minor: heterozygous defect



Can be due to drugs or mutations; running issues of anemia
Higher than normal oxidized hemoglobin
Amyl nitrate can be used to treat cyanide poisoning by oxidizing Hb which readily binds cyanide, producing cyanohemoglobin which keeps cyanide out of blood (and out of binding to cytochrome C oxidase) and then you get rid of cn