holoenzyme

A holoenzyme is an active enzyme composed of a protein moiety, the apoenzyme, and non-protein components such as cofactors or prosthetic groups. The non-protein part can be a metal ion, an organic molecule known as a coenzyme, or a tightly bound prosthetic group that remains associated with the enzyme.

Apoenzymes require these non-protein components to achieve catalytic activity. Cofactors may be inorganic ions (such as Mg2+ or Zn2+) or organic molecules derived from vitamins (such as NAD+, FAD, biotin, or coenzyme A). When the non-protein component is bound loosely, it can dissociate during catalysis, whereas prosthetic groups remain tightly bound, forming a holoenzyme.

Examples include the bacterial RNA polymerase holoenzyme, which comprises the core enzyme plus a sigma factor to enable promoter recognition and transcription initiation. The pyruvate dehydrogenase complex is a multi-subunit holoenzyme that relies on several cofactors, including lipoate and thiamine pyrophosphate. Carbonic anhydrase uses a tightly bound zinc ion as a prosthetic group to catalyze the hydration of CO2.

Role and significance: Holoenzymes allow integration of protein structure with required chemical cofactors, enabling regulated and efficient catalysis. Deficiencies in vitamins or metal ions can impair holoenzyme function, impacting metabolism, gene expression, and overall cellular physiology.