Superoxide generation from nitric oxide synthases.
Besides nitric oxide (NO), NO synthases (NOS) also produce superoxide ((*)O(2)()), a primary reactive oxygen species involved in both cell injury and signaling. Neuronal NOS was first found to produce (*)O(2)(-) in vitro. Subsequent studies revealed (*)O(2)(-) generation as a common property of all NOS isoforms. Although NOS was originally shown to produce (*)O(2)(-) under defined conditions such as substrate or cofactor depletion, recent enzymatic studies found that the reduction of oxygen to (*)O(2)(-) is an obligatory step in NO synthesis. Tetrahydrobiopterin appears to play a key role in preventing (*)O(2)(-) release from the NOS oxygenase domain. On the other hand, the NOS reductase domain is also capable of producing significant amounts of (*)O(2)(-). Increasing evidence demonstrates that (*)O(2)(-) generation is involved in both physiological and pathological actions of NOS.
Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Molecular and Cellular Biochemistry, The Ohio State University Medical Center, Columbus, Ohio 43210, USA. yong.xia@osumc.edu
Yong
Y
Xia
D000818:Animals; D002384:Catalysis; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D019001:Nitric Oxide Synthase