CuZnSOD

CuZnSOD, or copper-zinc superoxide dismutase, denotes a family of metalloenzymes that catalyze the dismutation of superoxide radicals. In humans, the term commonly refers to two major forms: the cytosolic SOD1 and the extracellular SOD3, both metal-dependent enzymes that protect cells and tissues from oxidative stress.

Each subunit binds one copper ion and one zinc ion and functions as a homodimer. The copper center participates in redox cycling between Cu2+ and Cu+, enabling rapid turnover of superoxide, while zinc plays a structural role that stabilizes the catalytically competent fold. The active site is coordinated by histidine residues and nearby ligands; in SOD1 a conserved disulfide bond further contributes to stability. Copper insertion is assisted by the copper chaperone CCS, and proper maturation is essential for activity.

CuZnSOD catalyzes the reaction: 2 O2- + 2 H+ -> O2 + H2O2. By converting superoxide to hydrogen peroxide and oxygen, it limits oxidative damage and modulates signaling pathways that rely on reactive oxygen species. Cytosolic SOD1 is found throughout the cell, while extracellular SOD3 is secreted and associated with extracellular fluids and matrix components.

Genetically, SOD1 encodes the cytosolic enzyme and is located on chromosome 21 in humans. Mutations in SOD1 cause familial amyotrophic lateral sclerosis, typically through misfolding and aggregation rather than loss of normal activity. CuZnSOD thus plays a central role in innate antioxidant defense and cellular redox homeostasis.