Allostery Flashcards
What is the homotrophic and heterotrophic effect
What happens when a positive modulate binds to the regulatory site of an allosteric enzyme
What is feedback inhibition
What does ATCase do
How is ATCase activity controlled
How is carbamoyl phosphate synthesised
Why does ATCase activity need to be controlled and what is the effect of increasing [CTP] on its activity
What is ATCase made up of
What is PALA
What is the active site of ATCase made up of
What happens when PALA binds to ATCase
What happens when CTP binds to ATCase
When are the R and T states of ATCase favoured
What is cooperatively
Draw the model for cooperatively
How do allosteric regulators modulate T to R equilibrium
What is the characteristics of the symmetry or MWC model
Conformational Equilibrium: The MWC model proposes that allosteric proteins exist in two distinct conformational states: the tense (T) state and the relaxed (R) state. These states differ in their affinity for ligands and their catalytic or signaling activity.
Symmetry: The model assumes that all subunits within the multimeric protein are structurally identical and undergo concerted conformational changes. In other words, when one subunit transitions from the T state to the R state, all other subunits in the protein undergo a similar conformational change simultaneously.
Ligand Binding: Ligand binding to one subunit of the protein stabilizes the R state and shifts the conformational equilibrium of the entire protein toward the R state. Conversely, ligand dissociation favors the T state.
Cooperativity: The MWC model explains cooperativity in ligand binding by postulating that ligand binding induces conformational changes that are communicated among subunits within the protein. This communication results in cooperative binding behavior, where the binding of one ligand molecule increases the affinity of neighboring subunits for ligand binding.
Equilibrium between T and R States: The equilibrium between the T and R states is governed by the conformational stability of each state and the free energy difference between them. Ligand binding alters this equilibrium by shifting the balance toward the R state (for activators) or the T state (for inhibitors).
Absence of Intermediate States: According to the MWC model, there are only two conformational states (T and R), and no intermediate states exist between them. This simplifies the model and makes it easier to analyze and understand.
Application to Allosteric Proteins: The MWC model is widely used to describe the behavior of allosteric proteins, including enzymes, receptors, and transporters, where ligand binding induces conformational changes and affects the protein’s activity or function.
What is the k system
What is the V system
What is the sequential model
Explain the symmetry model
Explain the relationship between the ligand binding to the receptor
What are the characteristics of allosteric enzymes
Why do allosteric enzymes display sigmoidal plots and what is positive cooperativity of allosteric enzymes
What does deoxygenated myoglobin look like
What is haem doming
What are the resonance structures of bound oxygen to iron
How is ligand binding to a single independent site quantified
What is the graphical representation of ligand binding ho a single independent site
What is the quaternary structure of haemoglobin
Show graphically how binding of oxygen to haemoglobin shows cooperativity and explain
Each hemoglobin molecule can bind up to four oxygen molecules. Hemoglobin exhibits what we call cooperative binding, as oxygen binding increases the affinity of hemoglobin for more oxygen. Increased affinity is caused by a conformational change, or a structural change in the hemoglobin molecule
Explain what state haemoglobin/ myoglobin would be in when oxygen is bound and show this graphically
When high fractional saturation of oxygen= R state = high affinity for oxygen
T state= low affinity for oxygen
These two states are in equilibrium
A shift to the left indicates increased hemoglobin affinity for oxygen and an increased reluctance to release oxygen and vice versa
How is the hill coefficient calculated
0- fraction of saturation
Explain the hill plot for myoglobin and haemoglobin
For myoglobin, which only has one subunit, the slope must be 1; for hemoglobin, the Hill coefficient is 2.8 in the high affinity state (R state), indicating a minimum of three interacting subunits, although there are four subunits in a molecule of hemoglobin.
A plot of log (Y/1-Y) vs log L is called a Hill plot, where n is the Hill coefficient. This equation is of the form: y = mx + b which is a straight line with slope n and y intercept of - log Kd.
n= hill coefficient so slope/gradient gives the hill coefficient
How does haem convert to the R state when oxygen binds
Draw a graph to represent the release of oxygen at different pressures
What promotes oxygen release from Hb
What does 2, 3 - BPG do
by binding to hemoglobin, 2,3-BPG decreases hemoglobins affinity for oxygen, thereby shifting the entire oxygen-binding curve to the right side. This is what allows the hemoglobin to act as an effective oxygen carrier in the body, unloading about 66% of oxygen to exercising tissue.
What is the role of fetal haemoglobin
What is the Bohr effect
The Bohr effect describes the change in affinity for oxygen haemoglobin has as a result of an increased partial pressure of CO2. It occurs due to the reaction between CO2 and H20, catalysed by carbonic anhydrase, to form carbonic acid. The carbonic acid then dissociates (breaks down) into Bicarbonate and H+ ions.
How does increasing co2 levels and decreasing pH promote oxygen release
it is the association of protons (H+ ions) with the amino acids in hemoglobin that cause a conformational change in protein folding, ultimately reducing the affinity of the binding sites for oxygen molecules.
This confirmation change results in a shift to the T form of Hb
How does sickle cell anaemia occur
