What type of modification can lead to irreversible changes in enzyme activity?

Proteolytic cleavage is a process where enzymes are activated or inactivated through the cleavage of specific peptide bonds within the protein structure. This modification leads to irreversible changes in enzyme activity because, once these bonds are broken, the original enzyme structure cannot be restored. This mechanism is pivotal for many enzymes that require activation by removal of regulatory portions of the protein.

In contrast, other modifications such as phosphorylation can be reversible; they often involve the addition or removal of phosphate groups, which do not permanently change the structural integrity of the enzyme. Similarly, allosteric modulation is also reversible, where binding of an effector molecule alters enzyme activity without permanently changing the enzyme structure. Denaturation, while it can lead to loss of activity, is generally not a controlled modification intended for enzyme regulation, and can sometimes be reversible if the conditions are restored. Thus, proteolytic cleavage is the modification that results in irreversible changes to enzyme activity, making it the correct choice.