cofactorfree

Cofactorfree is a term used in biochemistry and enzymology to describe enzymes, reactions, or catalytic systems that do not require external cofactors—such as metal ions, nucleotides, or organic prosthetic groups—to achieve catalysis. It is commonly used to distinguish reactions that rely solely on the protein’s active-site residues from those that depend on bound or transient cofactors.

In cofactor-free catalysis, the active site typically uses amino acid side chains—such as serine, histidine, aspartate, or cysteine—to perform acid-base chemistry, covalent catalysis, or stabilization of transition states. The reaction mechanism relies on the intrinsic properties of the enzyme rather than an external cofactor. Cofactor-free catalysis is often discussed alongside apoenzymes (protein components that require cofactors to be active) and holoenzymes (complete, cofactor-bound enzymes).

Examples and scope: Many serine proteases (for instance, some members of the serine protease family) operate without metal ions or organic cofactors and rely on catalytic residues to mediate peptide bond cleavage. Other enzymes, such as certain ribonucleases and glycosidases, can function without additional cofactors under appropriate conditions. By contrast, a large portion of metabolic enzymes depends on cofactors like metal ions (e.g., Mg2+, Zn2+) or organic carriers (e.g., NAD+, FAD, coenzyme A) for activity or regulation.

Applications and implications: The concept is relevant in enzyme engineering and industrial biocatalysis, where designing cofactor-free variants can simplify production, reduce costs, and improve stability in cofactor-deficient environments. It also aids in understanding fundamental catalytic strategies employed by proteins and in comparing different enzymatic mechanisms.

See also: Apoenzyme, Holoenzyme, Cofactor.