prosthetic group

Meaning: A prosthetic group is a non-polypeptide component bound tightly, usually permanently, to its protein by covalent bonds or very strong noncovalent interactions. It may be an organic molecule (heme, FAD, FMN, biotin) or a metal ion or cluster (Zn²⁺ in carbonic anhydrase, iron-sulfur clusters). The protein without it is the apoprotein (apoenzyme); the protein with it is the holoprotein (holoenzyme). The group supplies chemistry that amino acid side chains lack, such as binding O₂ (heme) or carrying electrons (FAD).

On the MCAT: Expect questions that ask you to name the prosthetic group of a protein (heme in hemoglobin, myoglobin and cytochromes) or to tell apo from holo forms. A passage may describe dialysis of an enzyme. If activity is lost after dialysis, the cofactor was loosely bound and dissociable (a coenzyme such as NAD⁺). If activity is kept, the cofactor was tightly bound, which fits a prosthetic group. Removing the group from an enzyme that needs it should abolish or sharply reduce activity.

Common confusion: Students use prosthetic group and coenzyme as if they were the same thing, or they think a prosthetic group is a protein subunit. It is not made of amino acids. Some textbooks treat prosthetic groups as a tightly bound subtype of cofactor or coenzyme, so the tightness of binding is the feature that settles which term applies.