Iron- and copper-dependent enzymes

Iron- and copper-dependent enzymes are a broad class of metalloproteins that utilize iron (Fe2+/Fe3+) or copper (Cu2+/Cu+) ions as essential cofactors to catalyze a wide range of biochemical reactions (Andreini et al., 2008). These enzymes play pivotal roles in fundamental biological processes such as cellular respiration, DNA synthesis, oxygen transport, and the neutralization of reactive oxygen species (Festa & Thiele, 2011). For instance, iron-dependent prolyl hydroxylases regulate the cellular response to hypoxia, while copper-dependent lysyl oxidases are required for the structural integrity of the extracellular matrix (Kagan & Li, 2003). Dysregulation of these enzymes or the homeostasis of their metal cofactors is implicated in various pathologies, including cancer, neurodegenerative diseases like Alzheimer's, and chronic inflammatory conditions (Bush, 2003). Therapeutic strategies targeting this group include small-molecule inhibitors that bind to the enzyme's active site or chelating agents that sequester the metal cofactors (Hentze et al., 2004). However, the broad distribution and essential nature of these metals across many physiological systems present significant challenges for achieving drug selectivity and minimizing systemic toxicity (Kim et al., 2008).

Other names

MetalloenzymesFe/Cu-dependent enzymesIron-dependent enzymesCopper-dependent enzymesMetal-dependent oxidoreductases

Inhibition of catalytic activity via active site binding or metal cofactor chelation (Kim et al., 2008).