Copper and copper-dependent enzymes (Cu)

Copper is an essential trace element that serves as a critical catalytic and structural cofactor for a diverse array of enzymes, collectively known as cuproenzymes, which are involved in vital biological processes such as cellular respiration, antioxidant defense, and connective tissue formation [1.1.1, 1.4.4]. Key copper-dependent enzymes include cytochrome c oxidase for mitochondrial energy production, superoxide dismutase 1 (SOD1) for reactive oxygen species scavenging, and lysyl oxidase (LOX) for collagen cross-linking [1.1.1, 1.4.2]. Dysregulation of copper homeostasis is central to genetic disorders like Wilson's disease, characterized by toxic copper accumulation, and Menkes disease, which involves systemic copper deficiency [1.1.1, 1.5.4]. Furthermore, copper plays a significant role in cancer progression, where it promotes angiogenesis, tumor growth, and metastasis [1.1.1, 1.2.3]. Therapeutic strategies targeting this system include copper chelators like penicillamine and trientine to remove excess metal, as well as zinc salts to block intestinal absorption [1.1.4, 1.3.3]. More recently, copper ionophores such as elesclomol and disulfiram have been investigated for their ability to induce cuproptosis, a novel form of regulated cell death, in malignant cells [1.2.1, 1.3.5]. However, modulating copper levels requires careful monitoring to avoid secondary copper deficiency, which can manifest as severe anemia, neutropenia, or neurological impairment [1.3.1, 1.5.4].

Other names

CuproenzymesCopper-binding proteinsCopper ionsCopper metabolism system

Therapeutic intervention involves the use of chelators to sequester and excrete excess copper, ionophores to transport copper into cells and induce cuproptosis, and inhibitors to block the activity of specific cuproenzymes like lysyl oxidase. Additionally, zinc salts are used to induce metallothionein in the gut, which sequesters copper and prevents its absorption.