Fig. (2) NOS isoforms and reactive oxygen species (ROS) production through electron flowing. A) NOS enzyme schematic structure with main cofactors. B) Normal electron flowing in NOS enzyme: electron from flavin derived cofactors goes to Heme domain together with, but faster than, the electron transfer from BH4; however, before the next catalytic cycle can proceed, the BH4 has to be reduced. These oxidations lead to limitation of ROS production. C: electron flowing through NOS enzyme in hypertension: there is a disruption in BH4 oxidation, leading to NOS uncoupling, reduced no production and, consequently, increased ROS.