Hemoglobin Flashcards
What is a gene family
A gene family is a group of similar genes that arose from duplication of a single original gene
The expression patterns of the genes within one family can change throughout time (some genes may never be expressed) - nonexpressed genes are pseudogenes
Name the different globin subunits. describe their expression patterns
Human largely express three types of hemoglobin , a, b, y
Y (gamma) Hb is fetal hemoglobin and is present as far as 7-8 months after birth - after this period, Hbb is expressed
Summarize gas transport (CO2 and O2) and pH regulation in humans
O2 is carried by hemoglobin
CO2 is either carried in the blood while bound to hemoglobin OR is converted to carbonate (HCO3-) by carbonic anhydrase and carried in the extracellular fluid
Compare and contrast myoglobin and hemoglobin structure and function
Myoglobin is a monomeric protein that can carry 1 O2 molecule - it is largely found in the tissues - its function is NOT cooperative
Hemoglobin is a tetrameric protein that can carry 4 O2 molecules - its function is cooperative
Both myoglobin and hemoglobin contain Fe2+
Myoglobin demonstrates a higher affinity for O2 than hemoglobin
Why is cooperativity important in hemoglobin function
To maintain efficiency both when loading and offloading O2
binding 1 unit of O2 causes the other subunits to have higher affinity for O2
releasing 1 unit of O2 causes the other subunits to have a lower affinity for O2
Define the T and R states of hemoglobin
T state (low affinity, tissue) R state (high affinity, respiration)
Describe the mechanistic effect of O2 binding to hemoglobin
In its native state, hemoglobin is in a position where Fe2+ is being pulled away from the porphyrin ring by a His residue
The binding of O2 realigns Fe2+ with the porphyrin ring and causes the other subunits to shift to a conformation that favors the R state
Why is CO poisoning bad
CO has incredibly high affinity for the binding sites on hemoglobin
CO will irreversibly lock hemoglobin in its R state, making it impossible to deliver oxygen to the body
What are the allosteric regulators that cause hemoglobin to have a reduced affinity for O2? Where is this useful? What category of allosteric effectors are these?
2,3 DPG, CO2, and H+ - locations with these conditions are usually in need of free O2
Concentrations of these molecules tend to be high in the tissues where catabolism is taking place
Negative heterotropic (different binding molecules as sites affected) allosteric effector
What is the allosteric regulator that causes hemoglobin to have an increased affinity for O2? Where is this useful? What category of allosteric effector is this?
O2
This is useful in the lungs where O2 must bind to Hb to be transported elsewhere in the body
O2 is a positive homotropic (same binding molecule as sites affected) allosteric effector
O2
This is useful in the lungs where O2 must bind to Hb to be transported elsewhere in the body
O2 is a positive homotropic (same binding molecule as sites affected) allosteric effector
What is the Bohr effect (isohydric shift)? What is its cause?
The reciprocal relationship exhibited by O2 and H+ binding on hemoglobin
In deoxyHb, His (neutral) and Asp (negatively charged) are close together. This encourages His to become protonated (become positively charged)
In HbO2, His and Asp are moved apart. This favors neutral His and causes the proton (H+) to fall off
Conformational shifts caused by the binding of oxygen slightly alters the pKa of Histidine to be less favorable to H+ binding
What is the function of 2,3-DPG, how does it work, and what is its importance
Negative allosteric effector of O2, highly negatively charged, ionically binds six residues in Hb, causing conformational changes that lower Hb affinity for O2 (easier dissociation in the tissues)
Important for adaptation to different O2 environments, as O2 levels decrease, 2,3-DPG levels increase
Increases the cooperative characteristics of hemoglobin
How does temperature affect hemoglobin function
Higher temperatures cause O2 to more readily dissociate from Hb
What category of genetic disease is sickle cell anemia
Homozygous recessive with heterozygous symptoms
What is the cause/effect of sickle cell disease
Point mutation in the B-globin gene - substitution of valine6 (bad) for glutamate6 (good) resulting in HbS (sickle)
Valine (hydrophobic) ends up on the surface of the globin subunit, creating a sticky patch that polymerizes with other defective HbS’s, forming fibers - The hydrophobic Val lodges in a pocket formed by Leu and Phe (also hydrophobic)
These fibers reduce the deformability of RBC’s, leading to vaso-occlusive symptoms, anemia, etc
