L8- Oxygen Transporters Flashcards
What prosthetic group do myoglobin and hemoglobin have in common?
Both proteins contain a heme prosthetic group.
What is the difference between a prosthetic group and a coenzyme?
A prosthetic group is firmly attached to a protein and usually cannot be removed during protein purification. A coenzyme is an organic molecule that is less firmly attached.
What is the oxidation number of the heme iron found in oxygenated myoglobin? What is the oxidation number of the heme iron found in deoxygenated myoglobin?
Iron is in its ferrous state (Fe2+) irrespective of oxygen binding in both myoglobin and hemoglobin.
What amino acid residue in hemoglobin binds iron?
Histidine (F8). Movement of this residue helps the protein sense whether or not O2 is bound to the heme group.
Carbon monoxide binds to isolated heme molecules much more tightly than oxygen. How is the CO binding affinity of hemoglobin attenuated?
The ferrous iron in isolated heme binds CO at a 180 degree angle. Histidine E7 in the active site of heme prevents optimal CO binding by forcing the binding geometry to be 120 degrees, which is the optimal binding orientation of oxygen.
What triggers myoglobin to undergo a conformational change when it binds oxygen?
When it binds to oxygen, the oxygenated ferrous ion moves into the plane of the porphyrin ring, pulling along some of the protein with it. This is mediated by histidine F8.
Describe the shape of the myoglobin oxygen dissociation curve. What does it suggest with regards to the protein’s kinetics?
Hyperbolic. This suggests that simple equilibrium processes are involved in binding and release.
Describe the shape of the hemoglobin oxygen dissociation curve. What does it suggest with regards to the protein’s kinetics?
Sigmoidal. A binding curve with this shape indicates cooperativity among multiple binding sites.
What is the role of myoglobin in muscle?
It delivers the oxygen required for metabolism in actively exercising muscle.
What is the role of hemoglobin?
It transports oxygen between the lungs and tissues.
How many oxygen molecules do myoglobin and hemoglobin bind to, respectively?
Myoglobin binds to one oxygen molecule whereas hemoglobin binds up to four oxygen molecules.
Myoglobin vs. hemoglobin: which one is an allosteric protein?
Hemoglobin is an allosteric protein. Myoglobin, which binds only a single molecule of O2, is not.
What is meant by the statement ‘the binding of oxygen to hemoglobin is cooperative’?
It means that binding of oxygen to one site influences the oxygen affinity of the remaining sites on Hb.
What does the Hill coefficient measure? What are its possible values and what do these values indicate?
It measures the sigmoidal character of a protein’s binding curve and indicates the degree of the protein’s cooperativity. A Hill coefficient of 1 means no sigmoidal character and no cooperativity. A Hill coefficient greater than 1 means positive cooperativity. Hill coefficients can also be less than one. In this case, binding one ligand inhibits binding of a second.
What is the Hill coefficient of myoglobin?
1 (one).
The cooperativity of oxygen in hemoglobin suggests that the heme groups communicate with each other. However, they are too far apart to do so directly. How is it that one heme group may affect the oxygen binding affinity of another heme group?
Heme groups communicate with one another through conformational changes that are transmitted across the hemoglobin subunit interfaces.
Oxyhemoglobin is said to be in which conformational state?
The relaxed state. (It has oxygen so it is relaxed.)
Deoxyhemoglobin is said to be in which conformational state?
The taut state.
Which hemoglobin conformational state has the greatest affinity for oxygen?
The relaxed state.
How do high CO2 and rising H+ levels (low pH) affect hemoglobin’s affinity for oxygen? What is this effect called?
Both CO2 and low pH promote the release of oxygen by lowering the oxygen affinity of hemoglobin. This is known as the Bohr effect.
Describe the physical movement that occurs between the subunits of hemoglobin when an oxygen molecule binds to a heme group.
When oxygen binds to a ferrous iron, one pair of alpha-beta subunits rotates by 15 degrees relative to the other pair of alpha-beta subunits in the hemoglobin heterotetramer.
Where on hemoglobin does carbon dioxide bind?
Carbon dioxide binds to the N-terminal amino groups of the alpha subunits. Note that this is different from carbon monoxide, which binds to the oxygen binding site.
Describe the mechanism by which the binding of carbon dioxide to hemoglobin reduces oxygen affinity.
Carbon dioxide reacts reversibly with an N-terminal amino group (in an alpha subunit) to form a carbamate. The carbamate groups form ionic bonds that stabilize the taut (deoxy) state of Hb, thereby lowering the oxygen affinity of hemoglobin.
Because they reduce the oxygen affinity of hemoglobin without binding directly to the site of oxygen binding, both carbon dioxide and protons are called ______________ effectors.
Negative allosteric.
