Chapter 9 - Hemoglobin
Terms in this set (17)
Hemoglobin vs Myoglobin
- allosteric protein in RBC
-cooperactivity in O2 binding and release
-enzyme like but not an enzyme - carries O2 from lungs and tissues
-also binds O2 but in a muscle cell
-stores O2 for release to mitochondria
How does cooperativity enhance O2 delivery by hemoglobin?
-In lungs hemoglobin becomes saturated with O2 such that 98% of O2 binding sites are occupied
-When it moves to tissues saturation level drops to 32% therefore 98-32=62% of potential O2 binding sites release O2 in tissues
-releases only part of O2 that is carried bc allosteric regulators released at tissues can further enhance O2 release
What is the Heme part of Hemoglobin and myoglobin?
It is the O2 binding molecul-protoporphyrin molecule with Fe2+
-hydrophobic except for 2 proportionate groups
Fe2+ Binding characteristics within Heme
Fe2+ has 6 attachments - 4 attached to heme ring - prosthetic gr., 1 attached to Hi of 'globulin' protein - promixal histadine, 1 left for O2 to bind
-There is also a His above the O2 binding site - prevents oxidation of Fe2+ to Fe3+, will bind to O2 to stabalize, limits acess to Fe2+
What is the difference between Deoxy and oxyhemoglobulin?
Deoxy - Iron ion lies slightly outside plane of phorphyrin - too lard to fit
Oxy - fits into the plane because of electron rearrangement of the iron
What are the properties of Globins?
-Increase solubility of heme - hydrophobic pocket for heme thats less prone to oxidation
-Protein arrangement - hydrophobes on side - hydrophiles on outside
-Myoglobin - single globin - single heme
-Hemoglobin - tetremer of globin subunits - 4 hemes
T and R state of Deoxy and Oxyhemoglobin
- similar to T state of aloosteric enzymes
-aplha/beta dimers linked extensively
-R state occurs upon O2 binding - ion changes and proximal His moves with iron
-Other subunits influenced and shift to R state- O2 binds more easily to other site
Structural transition at the iron ion
-directly transmitted to other subunits resulting in substantial changes in Quaternary structure that correspond to T - R state transition
-The rearrangement of the dimer interface provides pathway for communication between subunits therefore presence of O2 immediately communicated to others so subunits change from T to R together
What is the relationship between Protons and Carbon Dioxide
-H+ and CO2 are signals of muscle metabolism - O2 supply and demand
-H+ and pH (Bhor effect) - carbonic anhydrase converts CO2 and H2O to HCO3 and H+ - His pronated and stabilizes T state
-CO2 - additional effect of binding to Hb - binds terminal amine groups to form carbonates - stabilizes T state
What are the heterotropic effectors that enhance O2 release?
H+ and CO2
-hemoglobin responds to CO2 with decrease in O2 affinity therefore facilitating release of O2 in tissues with high CO2 concentration
-CO2 stabalizes deoxyhemolobin by reacting with terminal amino groups - carbonmate groups neg charged
What is the chemical basis of the Bhor effect?
In deoxyhem 3 AA residues form salt bridges that stabalize the T quaternary strucutre
-formation of a slat bridge depends on added porton on His-beta-146.
proximity of neg charge on Asp-beta-94 in deoxyhem favours pronation of this His
Heterotrophic regulation of hemeglobin
Heterotrophic regulation of hemeglobin by hydrogen ions and CO2 further increase O2 transporting efficiency of allosteric protein
What are the characteristics of 2-3-Bisphosphoglyerate (2,3-BPG)?
- neg charged allosteric regulator molecule
-binds to pocket that exists only when hemoglobin is in T state
-stabilizes T state of hemoglobin which facilitates release of O2
-binds to hemoglobin and decreases O2 affinity so 66% of O2 is released instead of smaller 8% - binds in pocket in T form in center of tetradimer hemo - interaction facilitated by ionic bonds between neg charges of BPG and pos ones from beta chain
Why does fetal Hemoglobin have less affinity for 2,3-DBP?
fetal hemoglobin as a2ya instead of a2b2 - with the y unit having Ser residue rather tehn His so 2.3-BPG does not bind as tightly = less T state = increased affinity for 02
What is Sickle cell Anemia?
-mutation in Beta unit results in hemoglobin S (HBS) - valine interact with eachother when HbS deoxygenated - results in 'sticky' ells that are also fragile
-hemoglobin aggrevates - clots
-erythrocytes rupture - anemia
- The AA alteration decreases solubility of deoxygenated but no oxygenated form of HbS therefore sickling results with high concentration of deoxy form of HbS
-large fibrous aggregates form from Hb that have bound together - deform cell
What is the difference between Hetero and Homo zygote?
Homo - 50% sickled
-symptomatic and possibly fatal
Hetero - 1% sickled
What are the characteristics of Malaria?
-Protozioan - spread by mosquitos - replicates in erythrocytes - anemia, fever, coma and death
-Prevalent in equaterial regions
-HbS containing erthyrocytes: rupture upon infection therefore provide resistence to Malaria - Heterozygotes get protection without sickle cell symptoms - selective pressure for HbS gene to persist in these populations