Multiple manganese-dependent enzymes

Multiple manganese-dependent enzymes represent a broad functional class of proteins that require manganese ions (Mn2+) as an indispensable cofactor for their biological activity. This group includes critical enzymes such as manganese superoxide dismutase (MnSOD or SOD2), which is the primary antioxidant enzyme protecting mitochondria from superoxide radicals (UniProt: P04179), and arginase, which is essential for the detoxification of ammonia in the urea cycle (UniProt: P05089). Other significant members include glutamine synthetase, which regulates nitrogen metabolism and glutamate levels in the brain, and pyruvate carboxylase, a key enzyme in gluconeogenesis (PubMed: 25603545). Because manganese is essential for the function of these diverse enzymes, its homeostasis is tightly regulated; however, chronic overexposure can lead to a condition called manganism, characterized by neurodegeneration in the basal ganglia and motor symptoms similar to Parkinson's disease (NIH: PMC4340611). Pharmacologically, manganese compounds are used as nutritional supplements or diagnostic contrast agents like mangafodipir, which also exhibits SOD-mimetic activity to provide cytoprotection against oxidative stress (DrugBank: DB00686). This target entry is considered 'incorrect' as a single therapeutic target because it refers to a heterogeneous collection of enzymes rather than a specific molecular entity.

Other names

Manganese-dependent enzymesMn-dependent enzymesManganese-activated enzymesManganese metalloenzymes

Manganese ions (Mn2+) serve as essential catalytic or structural cofactors; drugs may act as manganese supplements to restore enzyme activity, as chelators to remove excess manganese, or as manganese-complex mimetics (e.g., SOD mimetics) to perform enzymatic functions.