The catalytic activity of many enzymes depends on the presence of components called cofactors. Cofactors generally are either metal ions or small (relative to the enzymes) organic molecules called coenzymes.

Metal ions may assist in stabilizing the active conformation of the enzyme, or may play more specific roles in binding substrates and catalyzing reactions. Coenzymes fall into two groups:

• Metabolite coenzymes, most of which are derived from nucleotides

• Vitamin-derived coenzymes, which are synthesized from required dietary precursors.

These species are too numerous for us to consider all of them, so we will simply look at a few examples.

Metalloenzymes based on iron, zinc, copper, and cobalt are widespread, and a few enzymes have been found that contain nickel.

• Perhaps the largest group are those containing zinc, over 300 examples of which are known.

• An example: carbonic anhydrase catalyzes hydration of carbon dioxide to bicarbonate.
  • A zinc at the active site binds a water molecule, which is deprotonated by a nearby carboxylate.

  • The resulting hydroxyl then attacks the CO₂.

  Human Carbonic Anhydrase (2cab)

• The blue sphere in the middle of the structure is the zinc atom, Zn⁺⁺.

Of the metabolic coenzymes, the most widely used is adenosine triphosphate, ATP, which undergoes four types of reaction:

Line Structure of ATP	ATP in a Jmol Window

Notice that several different fragments of the ATP are transferred in these reactions: a phosphoryl, an AMP unit, and an adenosyl unit.