Allosteric effectors
Allosteric enzymes differ from other enzymes in that the plot of v as a function of [S], obtained
when studying the kinetics of the reactions catalyzed by allosteric enzymes, does not give a
branch of an equilateral hyperbola corresponding to the Michaelis-Menten equation (see fig.
1), but a sigmoid curve (S-shaped) (see fig. 1). We have already come across such a curve while
studying the hemoglobin ↔ oxyhemoglobin interconversion. In the case of allosteric enzymes
it also reflects a cooperative effect, i.e. the fact that the binding of the first substrate molecule
facilitates the binding of the second. Allosteric enzymes have an oligomeric quaternary
structure resulting from the assembly of a variable number of protomers joined by non-
covalent bonds which were studied in the previous chapter (see page 28). These oligomeric
structures bear a close resemblance with that of hemoglobin.
In addition to the catalytic site where the substrate binds, these enzymes have one or several
allosteric sites, which can be located on a different polypep- tide chain, and where allosteric
effectors (activators or inhibitors) having no structural analogy with the substrate, can bind.
FIG. 2-12. Kinetics of a reaction - catalyzed by an allosteric enzyme.
A. Allosteric activators
When an allosteric activator binds to the allosteric site, there results a slight modification of
the conformation of the enzyme - called allosteric transition- (reversible), which causes a
change of conformation of the active (catalytic) site. This site acquires a conformation more
favourable to the binding of the substrate; the affinity of the enzyme for the substrate increases
′
(𝐾𝑚 <𝐾𝑚 ). Even the shape of the curve can change from the sigmoid form to the hyperbolic
form (see fig. 1). As shown by figure 2, one can represent schematically, the allosteric transition
caused by the binding of the activator and its effects on the active site.
FIG. 2. Allosteric transition caused by an allosteric activator and allosteric inhibitors
B. Allosteric inhibitors
When an allosteric inhibitor binds to the allosteric site, an allosteric transition (also reversible)
takes place causing a change in the active site which now takes a conformation less favourable
to the binding of the substrate (see fig. 2). If v is plotted as a function of [S], the curve is again
′
a sigmoid but a decrease of the affinity of the enzyme for the substrate is observed (𝐾𝑚 > 𝐾𝑚 ).
In fact, this is only one of the various possible mechanisms because there are Active site having
bound the substrate several types of inhibitions.
Activation or inhibition by covalent modification
The activity of numerous enzymes is controlled, not by the formation of complexes between
enzymes and regulatory molecules, but by covalent modifications of the enzyme. Of such
modifications the best known is the phosphorylation/dephosphorylation of hydroxylated amino
acids; this modification, catalyzed in one direction by a kinase, and in the other by a
phosphatase, plays a very important role in numerous mechanisms, like transmission of nerve
impulse or metabolism of glycogen.
