Hemo and myo Flashcards
Heme proteins
-a group of specialized proteins that contain heme as a tightly bound prosthetic
Prosthetic group
coenzyme that is permanently associated with the enzyme or other protein and returned to its original form
Myoglobin and hemoglobin
heme is used to reversibly bind oxygen
Structure of heme
- heme is most prevalent porphyrin in humans
- uses iron held in the center of the heme molecule by bonds to the four mitrogens of the porphyrin ring
- the heme iron can form two additional bonds (6 total)
- (in heme and myo, one bond is with the R group of a histidine residue and one bond is to bind oxygen.
Myoglobin structure and function
- in heart and skeletal muscle
- oxygen reservoir
- oxygen carrier that increases rate of transportation within muscle cell
- single polypeptide
- alpha helix stretches
- -one histidine binds to iron and one histidine stabilizes binding of oxygen
Where is hemoglobin found and what is its function?
EXCLUSIVELY IN RED BLOOD CELLS
- transport oxygen from the lungs to the capillaries
Hemoglobin A structure
- -major adult hemoglobin
- 4 polypeptide chains, two alpha chains, two beta chains, all connected by noncovalent interactions
Hemoglobin transportation
- can transport 4 molecules of oxygen from lungs to peripheral tissues
- can transport CO2 and H+ from the peripheral tissues back to the lungs
- oxygen binding properties are regulated by interactions with allosteic effectors
Quaternary structure of hemoglobin
- tetramer can be envisioned as two identical dimers (alpha-beta) and each dimer is held together by hydrophobic interactions.
- dimers are attached by weak ionic and hydrogen bonds and the amount of polar bonding between the two dimers depends on whether or not oxygen is bound
forms of hemoglobin
T form(taut/tense): deoxygenated form of hemoglobin when no oxygen is bound and is the LOW OXYGEN AFFINITY FORM
R form(relaxed form): binding of oxygen to hemoglobin causes a break in some of the polar bonds between the dimers and is the HIGH OXYGEN AFFINITY FORM.
How many oxygen molecules can myoglobin and hemoglobin bind to?
Myoglobin can only bind to 1 oxygen
hemoglobin can bind to 4 oxygen
Degree of saturation with oxygen
- y axis
- varies between 0%(all sites are empty) and 100%(all sites are full)
Partial pressure of oxygen
- x axis
- P50 is partial pressure of oxygen to achieve half saturation of the binding sites.
- lower than P50 means high affinity
- higher than P50 means low affinity
Myoglobin curve
- hyperbolic shape
- very low P50
- very high oxygen affinity
- designed to bind oxygen at low partial pressure in muscle and release in response to oxygen demand
- high affinity in PO2 for peripheral tissues because it does not want to let go
Hemoglobin curve
- sigmoidal shape
- cooperative binding
- steep slope in the range that accounts for peripheral tissues so that the hemoglobin is more likely to respond to small changes in pressure and release O there
Heme-Heme interactions
- -binding of oxygen changes the structure of hemoglobin so that affinity increases for the others
- allows hemoglobin to deliver oxygen o tissues in response to small changes in partial pressure.
- interactions of dimers and subunits based on binding to oxygen
Bohr effect
- hemoglobin has less affinity for oxygen at lower pH.
- shifts curve to the right
- higher likelihood of complete unloading
CO2 bohr effect
- High levels of CO2 and lactic acid result in large amounts of carbonic acid
- large pH gradient between muscles and lungs to increase efficiency of hemoglobin as oxygen transporter.
- shifts graph to the right
Mechanism of Bohr effect
- Deoxygenated hemoglobin has a higher affinity for protons than oxygenated hemoglobin
- protonated version has stronger ionic interactions
- more stable T form
- lower affinity for Oxygen
2,3 BPG
- only binds to deoxygenated hemoglobin
- stabilizes T form
- decreases affinity for oxygen
- bind in pocket between beta globin chains in deoxyhemoglobin
- positive amino acids bind to negative 23BPG
- stabilize T form
- when oxygen is bound, 23BPG is expelled
- increased altitudes means more bpg and more efficient unloading
- 23BPG is necessary for life to make sure affinity is not too high and O cant unload
-lost when blood is in storage
CO2 binding effect
- usually bicarbonate ion form
- bound to N terminal amino group to form CARBAMINOHEMOGLOBIN
- stabilizes T form
- right shit in graph (less oxygen affinity)
- released in lungs
CO binding effect
- hemoglobin has much higher affinity for CO than O
- competes with O for spots
- high affinity for oxygen, less slots for O, very little oxygen transport
- shift graph to the LEFT
Fetal hemoglobin
- two alpha chains and two gamma chains
- gamma chains lack positively charged amino acids so dont bind with 23 BPG
- higher affinity for oxygen
- able to absorb oxygen from mom over placenta
Hemoglobin A1C
- formed by HbA by glycolation
- depends on concentration of glucose
- diabetics will have higher levels of HA1C
Sickle cell anemia characteristics
- hemoglobin S
- most common inherited blood disorder
- symptoms not seen until fetal hemoglobin is replaced with hemoglobin S
- increased susceptibility to infection
- cells have shorter life span
- glutamate is replaced by valine (more positive) so migrates slower under electrophoresis
Sickle cell anemia mechanisms stuff
- valine creates protrusion on the beta-globin that should fit into its site
- in T form, hemoglobin polymerizes and stiffens to distort the cell
- distorted cells interrupt the flow of blood and case anoxia
- high altitude, decreased pH, 23BPG increases sickling
HbSC
- one copy of HbS and one copy of HbC.
- variable symptoms
- some sickling but less paint
- HbC has mutation of LYS instead of GLU
