Nitrate Reductase Activity of Mitochondrial Aldehyde Dehydrogenase (ALDH-2) as a Redox Sensor for Cardiovascular Oxidative Stress

In 2002, mitochondrial aldehyde dehydrogenase (ALDH-2) was identified as an organic nitrate bioactivating enzyme. This so-called nitrate reductase activity denitrates nitroglycerin (glycerol trinitrate) to its 1,2-glycerol dinitrate metabolite and nitrite. This reaction relies on reduced thiols at the active site of the enzyme and on the presence of reduced dithiols as the electron source. During bioconversion of nitroglycerin, and also in the presence of reactive oxygen and nitrogen species, the active site thiols of ALDH-2 are oxidized and the enzyme looses its activity. We, therefore, speculated that ALDH-2 activity could be a useful marker for cardiovascular oxidative stress. Indeed, this hypothesis was supported by a number of studies, indicating that ALDH-2 activity is impaired in experimental animal models of increased oxidative stress and may be used for detection of an imbalance of mitochondrial and cellular redox state.