The cofactor BH4 is required for electron transfer in the eNOS catalytic cycle

The cofactor tetrahydrobiopterin (BH4) ensures endothelial nitric oxide synthase (eNOS) couples electron transfer to L-arginine oxidation (Berka et al. 2004). During catalysis, electrons derived from NADPH transfer to the flavins FAD and FMN in the reductase domain of eNOS and then on to the ferric heme in the oxygenase domain of eNOS. BH4 can donate an electron to intermediates in this electron transfer and is oxidised in the process, forming the BH3 radical. This radical can be reduced back to BH4 by iron, completing the cycle and forming ferrous iron again. Heme reduction enables O2 binding and L-arginine oxidation to occur within the oxygenase domain (Stuehr et al. 2009).

辅因子四氢生物蝶呤（BH4）确保内皮型一氧化氮合酶（eNOS）将电子转移与L-精氨酸氧化相耦合（Berka 等人，2004年）。在催化过程中，源自NADPH的电子转移到eNOS还原酶域中的黄素FAD和FMN上，随后转移到eNOS氧合酶域中的铁质血红素上。BH4能够向电子转移过程中的中间产物捐赠一个电子，并在这一过程中被氧化，形成BH3自由基。该自由基可被铁还原回BH4，从而完成循环并再次形成亚铁铁。血红素的还原作用使得氧分子与L-精氨酸的氧化反应得以在氧合酶域内进行（Stuehr 等人，2009年）。