Fig. 7

NADH oxidation by complex I. The loose- and tight-binding sites for the nicotinamide nucleotide are shown as red sphere, the redox state of the Fe–S cluster N1a and the FMN is indicated, as well as the position of the C = O group of the peptide bond between E95^F and S96^F. NADH binds to the tight position of the empty binding site pushing the C = O group towards N1a. Hydride transfer leads to formation of NAD⁺ in the tight position and of FMNH₂. Electron transfer (ET) from FMNH₂ to the substrate quinone via the chain of Fe–S clusters leads to the re-oxidation of FMN and the flip of the peptide bond squeezing the NAD⁺ into the loose position from which it easily dissociates to enable binding of the next NADH. In case that the electrons cannot escape from the complex, e.g., in the presence of a mostly reduced quinone pool, electrons from FMNH₂ are kept inside the complex leading to a reduction of N1a²¹. Reduction of N1a prevents the flip of the C = O group resulting in NAD⁺ bound to the tight position from which it cannot dissociate. This prevents further binding of NADH. Re-oxidation of the quinone pool leads to the oxidation of N1a enabling the release of NAD⁺