Theoretical studies of the second step of the nitric oxide synthase reaction: Electron tunneling prevents uncoupling

The full coupling of the second step of Nitric Oxide Synthase reaction is achieved by tunneling of the cofactor tetrahydrobiopterin electron to the protonated Compound II singlet (Cpd II-P), which raises the side reaction barrier. In the absence of this electron tunneling, uncoupling leading to toxic species becomes equally possible.154