Models of Allosteric Regulation

The regulation of allosteric enzymes is based on the idea that their subunits exist in two interchangeable
conformational states: relaxed (R) or tense (T).

In the R state, the subunit is active and has a higher ligand-binding affinity than in the T state. To date,
two models can be used to explain the molecular and kinetics of allosteric enzymes:[3, 4]

1. Symmetry Model

Also known as the Manod-Wyman-Changeux Concerted Model, the symmetry model is applied to
allosteric enzymes comprising dimers, each with catalytic sites.[1,3]

This model assumes that the two subunits exist in the same state, and the enzyme is present in the
equilibrium of R and T. Since the ligand or substrate of an allosteric enzyme binds preferentially to the R
state, the equilibrium shifts towards the R state as the substrate concentration increases.

The conformational change in one subunit is in concert with the other, maintaining the symmetry of the
enzyme. In other words, the enzyme in the symmetry model exists in either RR or TT and not in the RT
state.[3, 4]

2. Sequential Model

Unlike the other model, the sequential model does not assume that the enzyme exists in R and T
equilibrium, nor does it dictate that subunits of an allosteric enzyme must always exist in the same
conformational state.

In this model, the ligand-binding or substrate-binding induces a conformational change of the subunit
from T to R state to accommodate the binding. The conformational change of one subunit reshapes its
interface to the neighboring subunit, which consequently, alters the binding affinity of the neighboring
subunit.
As the concentration of the ligand or substrate increases, more subunits undergo a conformational
change to ‘fit’ with the ligand or substrate, which subsequently modifies the affinity of the other
subunits in the process.[1,3, 4]