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.