Uncoupling of the eNOS enzyme resulting in the net production of superoxide instead of the protective endothelial nitric oxide (eNO). This image depicts the eNOS enzyme reaction and resultant production of the protective antioxidant, anti-inflammatory gas product eNO. Oxygen reacts with the eNOS enzyme in which the tetrahydrobiopertin (BH4) cofactor has coupled nicotinamide dinucleotide phosphate reduced (NAD(P)H) enzyme with L-arginine to be converted to nitric oxide (NO) and L-citrulline. When eNOS uncoupling occurs the NAD(P)H enzyme reacts with O2 and the endothelial cell becomes a net producer of superoxide (O2•) instead of the protective endothelial NO. This figure demonstrates the additional redox stress placed upon the arterial vessel wall and capillaries in patients with MS, PD, and overt T2DM.