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Why can a protein enzyme lose its activity when its cofactor is removed?

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A multi-panel diagram illustrates how a substrate binds to an enzyme's active site through induced fit, leading to product formation, and shows how non-substrates and allosteric regulators can alter enzyme activity by binding to different sites on the enzyme. — Enzyme In the induced-fit theory of enzyme-substrate binding, a substrate approaches the surface of an enzyme (step 1 in box A, B, C) and causes a change in the enzyme shape that results in the correct alignment of the catalytic groups (triangles A and B; circles C and D represent substrate-binding groups on the enzyme that are essential for catalytic activity). The catalytic groups react with the substrate to form products (step 2). The products then separate from the enzyme, freeing it to repeat the sequence (step 3). Boxes D and E represent examples of molecules that are too large or too small for proper catalytic alignment. Boxes F and G demonstrate binding of an inhibitor molecule (I and I′) to an allosteric site, thereby preventing interaction of the enzyme with the substrate. Box H illustrates binding of an allosteric activator (X), a nonsubstrate molecule capable of reacting with the enzyme.

A protein enzyme often loses its catalytic activity when its cofactor is removed because the complete, functional enzyme—known as a holoenzyme—requires the nonprotein cofactor to perform its biological function. Without the cofactor, the remaining protein component, called the apoenzyme, is typically inactive.1

Cofactors are essential for several reasons:

Direct Participation: They often participate directly in biochemical reactions by assisting in the transfer of electrons, atoms, or functional groups between molecules.1
Substrate Binding: They help facilitate the binding of substrates to the enzyme’s active site, ensuring the reaction can occur.1
Structural Support: Some cofactors contribute to the overall three-dimensional shape of the enzyme, providing necessary structural stability.1

Because these components are integral to the enzyme's mechanism and structure, their removal prevents the enzyme from effectively catalyzing its specific reaction.1