However, in the presence of pathologic conditions like atherosclerosis and diabetes, the NOS function is altered, and the enzyme catalyzes the reduction of O2 to superoxide (O2−), a phenomenon that is generally referred to as “NOS uncoupling” [30,31,32,33,34,35,36,37,38,39,40,41], and has been linked to a limited bioavailability of tetrahydrobiopterin (BH4, also known as sapropterin) [42,43,44,45,46,47]. This evidence concerns the gene NOS1 and atherosclerosis.