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.
Xia
Yong
Y
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
D000818:Animals; D002384:Catalysis; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D019001:Nitric Oxide Synthase