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doi: 10.1016/j.fct.2017.07.050 10

The GCH1/BH4/DHFR axis operates independently of GPX4: guanosine triphosphate cyclohydrolase 1 (GCH1) catalyzes the rate-limiting step in the de novo synthesis of tetrahydrobiopterin (BH4) from GTP, producing BH4 as a potent radical-trapping antioxidant (RTA) that directly neutralizes lipid peroxyl radicals (LOO) and prevents membrane lipid peroxidation ( 2 ) a lipophilic radical-trapping antioxidant that detoxifies lipid peroxides where GPX4 access is limited