Oxygen Transport Flashcards
What are the functions of the proximal and distal histamines on a heme group?
Proximal - coordinates with Fe2++
Distal - oriented such that it forces an angled bond with O2 and prevents strong bonding with CO
What is the makeup of a heme group?
Iron (Fe2++) and porphyrin complex
Describe the structure of myoglobin
Single polypeptide that folds into a compact tertiary structure
Mostly nonpolar core that protects heme from H2O
Mostly polar surface
Describe the quaternary structure of hemoglobin
Made up of 4 subunits
Alpha and beta subunits held together via hydrophobic effect (nonpolar amino acids) to form a dimer
Two alpha-beta dimers held together via ionic and H bonds
What are a few factors that affect the ability of Hb to bind oxygen?
[O2] - positive effect at high pO2
pH - negative effect at low pH
[CO2] - negative effect at high pCO2
2,3-BPG - negative effect
Contrast T-form and R-form Hb
T-form (deoxy) - many weak ionic bonds between alpha-beta dimers, low O2 binding ability
R-form (oxy) - fewer weak ionic bonds between dimers, looser formation, higher O2 binding ability
What is positive cooperativity ?
When a T-form Hb subunit binds an oxygen molecule, the other 3 subunits are induced into R-form conformation
Describe the Bohr effect and the influence of low pH on Hb binding ability
Oxygenation of Hb results in proton disassociation
High [H+] (low pH) causes restoration of ionic bonds (T-form) and oxygen release
Helpful for O2 delivery to working tissues
How does Hb “sense” and transport CO2?
CO2 covalently binds to N-terminus of heme protein to form carbamylhemoglobin
Negative charge interacts with positive residue and promotes ionic bonding, stabilizing T-form and releasing O2
What is the function of 2,3-BPG in oxygen transport?
Participates in ionic bonding between beta subunits, stabilizes the T-form
If in hypoxic conditions (high altitude, exhaustion, etc.), BPG concentration increases and enhances oxygen delivery
Describe mutations that can result in decreased Hb solubility
Mutations that create points of polymerization or aggregation, causes distorted RBC shape and more readily-destroyed RBC’s
Mutations that change protein conformation such that the nonpolar core faces outward, causing Hb precipitation (Heinz bodies)
Describe a mutation that could increase Hb affinity for oxygen
Altered alpha-beta contacts or decreased BPG will increase R-form/T-form ratio
What is polycythemia? What could this condition be compensating for?
Increased RBC and Hb count
Could be compensating for increased Hb affinity for oxygen and, consequently, decreased oxygen delivery
How could a mutation decrease Hb affinity for oxygen? What is a possible consequence? Does this affect oxygen delivery?
Mutation that favors T-form stabilization or R-form destabilization
Could lead to cyanosis (deoxy blood)
Oxygen delivery will be okay as O2 disassociation isn’t disrupted
What sort of heme mutation could allow for oxidation of that heme?
Mutation in His that allows H2O to oxidize Fe2++
