Lecture 7 - Allosteric Control

Ligand

Any compound that will bind to a receptor

Hyperbolic kinetics

(Most enzymes) the rate of enzyme activity increases as the ligand concentration increases until it reaches saturation

Sigmoidal kinetics

Enzymic rate modulated by the binding of multiple ligand molecules and effectors

Characteristics of proteins showing sigmoidal kinetics

Proteins which use co - operative binding

Co operative binding

When the first substrate molecule binds to its binding sit on one of the sub units, it increases the affinity of the second so it binds easier

allosteric proteins…

show co operativity and sigmoidal kinetics

effect of positive effectors

increase affinity

effect of negative effectors

decrease affinity

effect of positive effectors on sigmoidal curve

move s curve left

effect of negative effectors on sigmoidal curve

move s curve right, shallower slope

2 models to describe allosteric effects

Concerted model and sequential model (most enzymes follow a mix)

Concerted model of allosteric effects

One substrate binding to T form causes all sub units to convert to R form

Sequential model of allosteric effects

One substrate binding to T form converts one sub unit to R form making it easier for substrate to bind to other sub units

States which sub units exist in

T and R

What is the T state

Low affinity for the substrate

What is the R state

High affinity for the substrate

Positive effectors on the sub units

Stabilise the R state of the sub units

Negative effectors on the sub units

Stabilise the T state of the sub units

Cell with high energy stores have

High ATP, low ADP/AMP, low NAD+

Positive effector in glycogenolysis: Glycogen phosphorylase

AMP

Negative effector in glycogenolysis: glycogen phosphorylase

ATP

Positive effector in glycolysis: hexokinase, PFK, pyruvate kinase

AMP

Negative effector in glycolysis: hexokinase, PFK, pyruvate kinase

ATP

Positive effector of pyruvate deHase (TCA cycle)

AMP, NAD+

Negative effector of pyruvate deHase (TCA cycle)

NADH

Negative effector of citrate synthase (TCA cycle)

ATP

Positive effector of isocitrate deHase (TCA cycle)

ADP

Negative effector of isocitrate deHase (TCA cycle)

NADH