holoenzymes

A holoenzyme is the active form of an enzyme, consisting of an apoenzyme (the protein component) together with one or more cofactors required for catalytic activity. The term contrasts with apoenzyme, which is inactive by itself. Cofactors can be inorganic metal ions (such as Mg2+, Zn2+, or Fe2+), organic molecules called coenzymes, or tightly bound non-protein groups known as prosthetic groups. When the cofactor remains tightly bound to the enzyme, the complex is often called a holoenzyme; when the cofactor is absent, a partially active or inactive form is an apoenzyme.

Coenzymes are usually loosely bound organic molecules that donate or accept chemical groups during catalysis (e.g., NAD+, FAD, coenzyme A). Prosthetic groups are cofactors that stay bound throughout catalysis, often covalently or tightly associated (e.g., the zinc in carbonic anhydrase, the heme in cytochrome c oxidase).

In bacteria, RNA polymerase holoenzyme consists of the core enzyme plus the sigma factor, enabling promoter recognition. Other holoenzymes include carbonic anhydrase with zinc prosthetic group; pyruvate dehydrogenase complex as a multi-enzyme holoenzyme requiring several cofactors (TPP, lipoamide, FAD, NAD+, CoA). In general, holoenzymes may be single proteins or multi-subunit assemblies.

Holoenzyme formation can be regulated by cellular conditions, availability of cofactors, and post-translational modifications. Deficiencies in cofactors can reduce enzyme activity and contribute to metabolic disorders.