What is allosteric regulation?

Question

I've found multiple definitions for allosteric regulation and struggling to understand which one is correct. My text book says:

'Another way of regulating enzyme activity is through allosteric regulation. This is where an inhibitor binds to a different part of the enzyme, called an effector site, which changes the shape of the enzyme. This binding can occur at any time. Product can only be formed (and released) if the inhibitor, I is not bound to the enzyme, E. Assume that binding of the enzyme to the substrate or the inhibitor is independent of one another so that the inhibitor, I, can bind to both the free enzyme, E and the enzyme-substrate complex, C1, and the substrate, S, can bind to both the free enzyme and the enzyme-inhibitor'

What I'm struggling with is if the inhibitor changes shape of the enzyme then how can the substrate still bind to the enzyme-inhibitor complex? Or does it just change the enzyme so that no reaction can occur and the substrate can still bind to it?

Thanks

Answer 1

This question really boils down to semantics, and the definition can be clarified by discussing enzyme regulation in general. The 3 main ways that enzymes can be inhibited are through the following mechanisms: competitive inhibition, non-competitive inhibition, and uncompetitive inhibition. In competitive inhibition, the inhibitor binds directly to the active site and blocks the substrate from binding (so they are "competing" for the active site, hence "competitive inhibition"). Non-competitive and uncompetitive both involve the inhibitor binding to a separate regulatory site on the enzyme that is different from the active site (the second sentence of your book's definition of allosteric regulation). However, we have to differentiate between the two, and a nice, concise delineation can be found here. This page states:

While uncompetitive inhibition requires that an enzyme-substrate complex must be formed, non-competitive inhibition can occur with or without the substrate present.

Therefore, your book's definition is more in-line with non-competitive inhibition. I'd encourage you to look at this page for a more thorough read, and because they have a nice simple illustration that might help put it in perspective.

Here's a more abbreviated answer:

Inhibitors may change the active site to prevent substrate binding, but that's not the only mechanism of inhibition. Specifically, non-competitive inhibitors may limit the ability of the enzyme to carry out its action without changing the shape of the substrate binding site (see this figure).

Final thought If you actually look at the etymology of the word "allosteric," its word roots come from the Greek allos that means "other or another" and from the Greek stereos that just means "solid or object." So in actual etymological terms, it's a more general term that should apply to both uncompetitive and non-competitive inhibitors because both bind at some other or allosteric site on the enzyme. However, the way your book defines it is more like the definition of a non-competitive inhibitor.