CH4 | Allosteric Interactions (PT2) Flashcards
What are allosteric modulators?
Specific molecules that bind reversibly to a protein at a site separate from the binding site, altering the protein’s activity and conformation.
What is an allosteric protein?
A protein with an “other site” (allosteric site), distinct from its active site, where allosteric modulators bind to induce a change.
What are the two possible roles of allosteric modulators? What is the role of each؟
Inhibitors: they can inhibit or decrease the activity of an enzyme by binding to it and stabilizing a conformation that is less favorable to bind to a substrate molecule.
Activators: they can also activate, or enhance the activity of an enzyme by binding to it and stabilizing the active conformation of the protein that readily binds to a substrate molecule.
Can allosteric modulators and ligands bind at the same site on a protein?
No, allosteric modulators bind at a site separate from the ligand binding site.
What is homotropic allostery?
Homotropic allostery occurs when the normal ligand and the allosteric modulator are the same molecule.
What is heterotropic allostery?
Heterotropic allostery occurs when the allosteric modulator is a different molecule than the normal ligand.
Can a protein experience both homotropic and heterotropic allosteric interactions? Why?
Yes, some proteins have two or more modulators, allowing for both homotropic and heterotropic interactions to occur. This depends on whether a modulator is identical to or different than a ligand.
What factors affect hemoglobin’s ability to reversibly bind oxygen?
Hemoglobin’s oxygen-binding is affected by four main factors:
- pO₂ (via heme-heme interactions),
- pH of the environment,
- pCO₂,
- and (2,3-BPG) levels.
Why are pO₂, pH, pCO₂, and 2,3-BPG called allosteric effectors of hemoglobin?
They are called allosteric effectors because their binding at one site of the hemoglobin molecule impacts the binding of oxygen to heme groups at other locations on the molecule.
What mediates the allosteric effects that result in cooperativity in hemoglobin?
Allosteric effects leading to cooperativity are mediated by conformational changes transmitted between subunits of the hemoglobin molecule.
What are three key characteristics of a sigmoid binding curve?
A sigmoid binding curve is diagnostic of cooperative binding, permits a sensitive response to changes in ligand concentration, and is essential for the function of many multi-subunit proteins like hemoglobin.
Besides oxygen, what other molecules or ions can hemoglobin (Hb) transport?
Hb can transport carbon dioxide (CO₂), protons (H⁺), 2,3-bisphosphoglycerate (2,3-BPG), carbon monoxide (CO), and nitric oxide (NO).
How is CO₂ binding to hemoglobin (Hb) related to oxygen binding?
CO₂ binding to Hb is inversely related to oxygen binding. This means that when CO₂ levels are high, Hb’s affinity for oxygen decreases, and vice-versa.
How does carbon dioxide (CO₂) bind to hemoglobin, and what does it form?
CO₂ binds as a carbamate group to the α-amino group at the amino-terminal end of each globin chain, forming carbaminohemoglobin.
What factors influence the binding of oxygen to hemoglobin
The binding of oxygen to hemoglobin is significantly influenced by pH and the concentration of CO₂ ([CO₂]).
What are the effects of CO₂ directly binding to hemoglobin?
Direct CO₂ binding stabilizes the T-form (deoxy) of hemoglobin, decreases its affinity for oxygen, and shifts the oxygen dissociation curve to the right.
How does the formation of carbamate indirectly induce the Bohr effect?
The formation of carbamate releases a proton (H⁺) into the solution. This increase in H⁺ concentration lowers the pH, thus indirectly inducing the Bohr effect.
What is the Bohr effect, briefly?
The Bohr effect is a phenomenon where increased CO2 levels and decreased pH in the blood reduce hemoglobin’s affinity for oxygen, thereby facilitating oxygen release to tissues.
Why is carbonic anhydrase important for CO₂ transport in the blood?
CO₂ has poor solubility in aqueous solutions. Carbonic anhydrase increases CO₂’s solubility, allowing for its efficient transport.
Why is the interconversion of CO₂ and bicarbonate important?
The interconversion of CO₂ and bicarbonate is crucial for regulating oxygen binding and release in the blood.
Why should O₂ and CO₂ be carried by hemoglobin in the blood?
O₂ and CO₂ are poorly soluble in aqueous solutions and can form bubbles, potentially blocking circulation. Hemoglobin helps transport them safely and prevents these complications.
Describe the relationship between CO₂ and O₂ levels and hemoglobin’s affinity for each in peripheral tissues.
In peripheral tissues, where CO₂ is high and O₂ is low, hemoglobin (Hb) has a high affinity for CO₂ (loading) and a low affinity for O₂ (unloading).
Describe the relationship between CO₂ and O₂ levels and hemoglobin’s affinity for each in the lungs.
In the lungs, where CO₂ is low and O₂ is high, Hb has a low affinity for CO₂ (unloading) and a high affinity for O₂ (loading).
What is the approximate oxygen saturation of hemoglobin in arterial blood?
In arterial blood (passing from the lungs to the peripheral tissues), hemoglobin is about 96% saturated with oxygen.
