Oxalate oxidase (OXO)

Oxalate oxidase is a manganese-dependent enzyme, belonging to the cupin superfamily, that catalyzes the aerobic oxidation of oxalate into carbon dioxide and hydrogen peroxide (UniProt: P15290). While naturally occurring in plants like barley and wheat where it is known as germin, it is not expressed in humans. This enzyme has emerged as a critical therapeutic target for managing hyperoxaluria, a metabolic disorder characterized by high urinary oxalate levels that lead to recurrent kidney stones and progressive renal damage (PubMed: 27535324). Therapeutic applications involve the oral administration of the enzyme, which acts locally within the gastrointestinal tract to degrade oxalate before it can be absorbed into the systemic circulation. By reducing the intestinal absorption of oxalate, the enzyme effectively lowers the metabolic load on the kidneys and decreases the formation of calcium oxalate crystals. Clinical candidates such as reloxaliase (ALLN-177) have been developed to utilize this mechanism for treating both primary and enteric hyperoxaluria (ClinicalTrials.gov: NCT03456830). This approach offers a non-systemic intervention to prevent the long-term complications of systemic oxalosis.

Other names

GerminOxalate:oxygen oxidoreductase

Catalytic degradation of dietary and endogenous oxalate within the gastrointestinal lumen to prevent systemic absorption and subsequent renal excretion.