Allosteric Regulation of Energy Metabolism Flashcards
What are ligands
Other molecules proteins bind to, can be substrates, hormones or compounds that regulate protein activity
What do most enzymes exhibit
Hyperbolic kinetics
What is hyperbolic kinetics
the rate of enzyme activity increases as the ligand concentration increases until it reaches saturation
What do allosteric molecules typically exhibit
Sigmoidal kinetics
What is sigmoidal kinetics
At low concentrations of substrate there is a gradual and slow increase in rate of enzyme activity, it then rapidly increases until max is reached due to the presence of allosteric effectors
What are the characteristics of proteins showing sigmoidal/cooperative kinetics
Composed of two or more sub-units.
The sub-units can exist in two different shapes.
Describe co-operative binding/co-operativity
When the first [substrate] molecule binds to its binding site on one of the sub-units, it increases the affinity of the second sub-unit for the second [substrate] molecule, so that the second molecule binds more easily to its binding site.
It gives rise to the sigmoidal curve
What are allosteric proteins
Proteins that show co-operativity and sigmoidal kinetics with regard to their substrate as
the enzyme subunits are also able to bind additional molecules (ligands) that are not their substrates e.g. effectors
What do effectors do
Binding of effector influences affinity of the protein sub-units for the ligand
Positive effectors increase affinity
Negative effectors decrease affinity
How do negative effectors work
Binding of the negative effector to its ligand binding site prevents the enzyme’s active site from becoming accessible to the substrate
How do positive effectors work
Binding of the positive effector to its ligand binding site makes the enzyme’s active site more accessible to the substrate
How do negative effectors impact the sigmoidal curve
The velocity against Substrate graph shifts from
left to right in presence of -ve effector and the slope is shallower in presence of -ve effector as a larger change in substrate for the same change in velocity is needed
(Until saturation, lower v for same S than when no effector)
How do positive effectors impact the sigmoidal curve
The velocity against Substrate graph shifts from right to left in presence of +ve effector and The slope is steeper in presence of +ve effector. A smaller change in substrate is needed for the same change in velocity. (Until saturation, higher v for same S than when no effector)
What two models are used to describe allosteric effects
Concerted model and sequential model
What is the converted/ Monad Wyam Changeux model
Sub-units of an enzyme can exist in only two forms: Tense (T) and Relaxed (R)
Cannot have mixed molecules (either R or T)
T form has low affinity for the substrate
R form has high affinity for substrate
when the substrate binds to T form it causes all sub-units to convert to R form because the R form has higher affinity for substrate than T form, enzyme activity increases rapidly after each enzyme molecule has bound one substrate molecule
What is the sequential model/ Koshland model
Sub-units can exist in two forms (T and R)
Can have mixed molecules
T has low affinity for the substrate
R has high affinity for substrate
when substrate binds to T form it causes the sub-unit to which it binds to convert to R form and makes it easier for substrate to bind to the other sub-units (sequential conversion from T to R) because the affinity for substrate increases once one sub-unit has converted to R form, activity increases rapidly after protein has bound one substrate molecule
What are the similarities between the concerted and sequential models
In both models:
Positive effectors stabilise the high affinity (R) form of the sub-units
Negative effectors stabilise the low affinity (T) form of the subunits
What happens to a compound if it’s concentration increase the cell increases
Will act as an effector of an allosteric enzyme
What happens to a compound as its concentration decreases in the cell
It’s effect as an effector of an allosteric enzyme decreases
What is the net effect of allosteric regulation of glycolysis in a cell with high energy stores
If a cell has high energy stores it will:
Store energy in the form of ATP then…
Store energy in the form of glycogen or lipid (synthesise fatty acids then TAG)
What is the net effect of allosteric regulation of glycolysis in a cell with low energy stores
If a cell needs energy it will:
Release energy generating nutrients from stores
These will go through the energy generating pathways to yield ATP
What is AMP a positive effector of in glycogenolysis
Glycogen phosphorylase
What is AMP a positive effector of in glycolysis
Hexokinase, phsophofructokinase (PFK), pyruvate kinase
What is AMP and NAD a positive effector for in the TCA cycle
Pyruvate debase and citrate synthase
What is ADP a positive effector of in the TCA cycle
Isocitrate deHase
What is ATP a negative effector for in glycogenolysis
Glycogen phosphorylase
What is ATP a negative effector for in glycolysis
Hexokinase (HK)
Phosphofructokinase (PFK)
Pyruvate kinase (PK)
What is NADH a negative effector for in the TCA cycle
Pyruvate deHase and Isocitrate deHase
What is ATP a negative effector for in the TCA cycle
Citrate synthase
