superoxide dismutase

Superoxide dismutase converts superoxide anion, a highly reactive ROS byproduct of oxidative phosphorylation and the respiratory burst of neutrophils/macrophages, into hydrogen peroxide and molecular oxygen: 2 O2•− + 2H+ → H2O2 + O2. Hydrogen peroxide is subsequently neutralized by catalase (to water and oxygen) or glutathione peroxidase (using reduced glutathione), preventing accumulation of toxic ROS that would otherwise generate hydroxyl radicals via the Fenton reaction and cause lipid peroxidation, protein oxidation, and DNA damage.

There are three main isoforms in humans: Cu/Zn-SOD (SOD1), found in the cytoplasm; Mn-SOD (SOD2), located in mitochondria; and extracellular SOD (SOD3), which is Cu/Zn-dependent and secreted into the extracellular matrix and plasma.

Clinical significance: Mutations in SOD1 are a well-known cause of familial amyotrophic lateral sclerosis (ALS), accounting for ~20% of familial cases, thought to arise from a toxic gain-of-function (protein aggregation) rather than loss of antioxidant activity. SOD is also part of the oxidative burst pathway in phagocytes (along with NADPH oxidase, myeloperoxidase), important in innate immunity; deficiencies in downstream enzymes (e.g., myeloperoxidase deficiency) or NADPH oxidase (chronic granulomatous disease) are tested board topics related to this pathway. SOD activity and oxidative stress are also implicated in aging, atherosclerosis, ischemia-reperfusion injury, and neurodegenerative diseases (Parkinson's, Alzheimer's).

Board relevance: Know the reaction catalyzed by SOD, its role in the ROS detoxification pathway (superoxide → hydrogen peroxide → water), its mitochondrial vs cytoplasmic isoforms, and its link to familial ALS (SOD1 mutations).