Copper-dependent enzymes

Copper-dependent enzymes, also known as cuproenzymes, are a diverse group of proteins that utilize copper ions as essential cofactors to catalyze critical biochemical reactions, particularly those involving oxygen and electron transfer (Lutsenko, 2010, NIH). Key members of this class include cytochrome c oxidase for mitochondrial respiration, superoxide dismutase 1 (SOD1) for antioxidant defense, and lysyl oxidase (LOX) for the cross-linking of collagen and elastin in the extracellular matrix (UniProt). Dysregulation of copper homeostasis or genetic mutations in these enzymes lead to severe pathologies, including Wilson disease (copper overload), Menkes disease (copper deficiency), and various cancers where copper promotes angiogenesis and metastasis (StatPearls). Therapeutic strategies targeting this class include chelating agents like penicillamine to remove excess copper and novel ionophores like elesclomol that induce a copper-dependent form of regulated cell death known as cuproptosis in cancer cells (Tsvetkov et al., 2022, Science). Because copper is a fundamental trace element, pharmacological modulation must be carefully managed to avoid systemic deficiency, which can manifest as hematological disorders or irreversible neurological damage.

Other names

CuproenzymesCopper-containing enzymesCopper metalloenzymes

Copper chelation to reduce systemic or local copper levels; Copper ionophore-mediated transport to induce cuproptosis; Direct inhibition of specific cuproenzyme catalytic sites.