title: Reciprocal regulation of cellular nitric oxide formation by nitric oxide synthase and nitrite reductases.
abstract: Our mini-review focuses on dual regulation of cellular nitric oxide (NO) signaling pathways by traditionally characterized enzymatic formation from L-arginine via the actions of NO synthases (NOS) and by enzymatic reduction of available cellular nitrite pools by a diverse class of cytosolic and mitochondrial nitrite reductases. Nitrite is a major metabolic product of NO and is found in all cell and tissue types that utilize NO signaling processes. Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping enzyme responsible for cellular uric acid formation via enzymatic conversion of hypoxanthine and xanthine. It has become apparent that XOR possesses multi-functional enzymatic activities outside the realm of xanthine metabolism and a small but significant literature also established a compelling functional association between administered sodium nitrite, XOR activation, and pharmacologically characterized NO transductive effects in positive cardiovascular function enhanced pulmonary perfusion, and protection against ischemia/reperfusion injury and hypoxic damage and oxidative stress. Similar positive vascular and cellular effects were observed to be functionally associated with mitochondrial aldehyde dehydrogenase and cytochrome c/cytochrome c oxidase. The profound implications of a reciprocal regulatory mechanism responsible for cytosolic and mitochondrial NO production are discussed below.
authors.affiliation: Neuroscience Research Institute, State University of New York - College at Old Westbury, Old Westbury, NY 11568-0210, USA. gstefano@sunynri.org
authors.forename: George B
authors.initials: GB
authors.lastname: Stefano
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kream
mesh_terms: D000444:Aldehyde Dehydrogenase; D001120:Arginine; D003600:Cytosol / Q000378:metabolism*; D003576:Electron Transport Complex IV; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D055414:Myocardial Perfusion Imaging / Q000379:methods; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009572:Nitrite Reductases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014968:Xanthine Dehydrogenase / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D014968:Xanthine Dehydrogenase; D000444:Aldehyde Dehydrogenase; D009572:Nitrite Reductases; D003576:Electron Transport Complex IV