<P> Vitamin precursors of NAD were first identified in 1938, when Conrad Elvehjem showed that liver has an "anti-black tongue" activity in the form of nicotinamide . Then, in 1939, he provided the first strong evidence that niacin is used to synthesize NAD . In the early 1940s, Arthur Kornberg was the first to detect an enzyme in the biosynthetic pathway . In 1949, the American biochemists Morris Friedkin and Albert L. Lehninger proved that NADH linked metabolic pathways such as the citric acid cycle with the synthesis of ATP in oxidative phosphorylation . In 1958, Jack Preiss and Philip Handler discovered the intermediates and enzymes involved in the biosynthesis of NAD; salvage synthesis from nicotinic acid is termed the Preiss - Handler pathway . In 2004, Charles Brenner and co-workers uncovered the nicotinamide riboside kinase pathway to NAD . </P> <P> The non-redox roles of NAD (P) were discovered later . The first to be identified was the use of NAD as the ADP - ribose donor in ADP - ribosylation reactions, observed in the early 1960s . Studies in the 1980s and 1990s revealed the activities of NAD and NADP metabolites in cell signaling--such as the action of cyclic ADP - ribose, which was discovered in 1987 . The metabolism of NAD remained an area of intense research into the 21st century, with interest heightened after the discovery of the NAD - dependent protein deacetylases called sirtuins in 2000, by Shin - ichiro Imai and coworkers at the Massachusetts Institute of Technology . </P>

Where is most nadh oxidized to nad+