How can changes in pH cause an enzyme to lose its function?

Enzymes are proteins whose biological function depends on a specific three-dimensional structure, which is determined by their amino acid sequence. Changes in pH can cause an enzyme to lose its function through a process called denaturation.12

When an enzyme is exposed to pH levels outside of its optimum range, the altered acidity or basicity disrupts the weak noncovalent bonds—such as hydrogen bonds and hydrophobic interactions—that maintain the protein's native shape. This disruption causes the enzyme to unfold or lose its structural integrity. Because the enzyme's active site is a precise groove or pocket formed by this specific folding pattern, any deformation of the protein molecule prevents the substrate from binding correctly, thereby destroying the enzyme's catalytic ability.321

While some proteins can undergo renaturation if conditions are restored, the denaturation of many enzymes is irreversible, resulting in a permanent loss of biological activity. Consequently, most living systems utilize buffering mechanisms to maintain a constant pH and protect these essential catalysts.23