Figure 4.

NOS enzyme productive and futile cycling during catalysis. The reduction of ferric enzyme (kr) is the rate‐limiting step for the NO biosynthetic reactions (central linear portion). This electron transfer is needed to reduce the ferric haem before each catalytic step (kr, kr′) and also to reduce the BH4 radical between the Arg and NOHA oxidation reactions (kr′). The kcat1 and kcat2 are the conversion rates of the NOS haem‐dioxy species (Fe^IIO₂) to products in the L‐Arg and NOHA reactions respectively. The ferric haem‐NO product complex (Fe^IIINO) can either release NO according to rate kd as part of a productive cycle or be reduced by the reductase domain according to rate kr ′′′ to a ferrous haem–NO complex (Fe^IINO), which reacts with O₂ according to rate kox in an NO dioxygenase reaction as part of a futile cycle, to generate nitrate and the ferric enzyme.