Metalloenzymes

Metalloenzymes are enzymes whose catalytic activity depends on a metal ion or metal-containing cofactor. The metal is typically coordinated in the active site by amino acid ligands and may be tightly bound as part of the enzyme’s structure or act as a reusable cofactor. Common metals involved include zinc, iron, copper, manganese, nickel, cobalt, and, in some systems, molybdenum or magnesium. Metalloenzymes encompass a large and diverse set of enzymes and are essential for many metabolic processes, including hydrolysis, redox reactions, and group transfer.

Examples and categories of metalloenzymes span a wide range. Zinc-dependent hydrolases such as carbonic anhydrase and several disaccharidases use Zn2+ to polarize substrates and activate water. Supramolecular systems include copper- and zinc-containing superoxide dismutases, which catalyze the dismutation of superoxide. Iron-centered enzymes include heme enzymes like catalase and cytochromes, as well as non-heme iron enzymes that perform oxygen activation and various oxidations. Iron-sulfur cluster enzymes participate in electron transfer and catalytic redox chemistry. Nickel-containing enzymes such as urease and some hydrogenases perform acid-base or redox reactions. Manganese and molybdenum enzymes also play key roles in oxidation–reduction and oxygen transfer chemistry.

Mechanistically, metals often function as Lewis acids to activate substrates, stabilize negative charges, or generate reactive intermediates such as metal-oxo species. Redox-active metal centers enable electron transfer and catalytic cycles that would be difficult with organic cofactors alone. The activity of metalloenzymes is influenced by metal availability and homeostasis; chelating agents can inactivate them, and metal dysregulation is linked to disease. Metalloenzymes are important in physiology, medicine, and industry, and many pharmacological targets focus on their metal-dependent mechanisms.