Some key cellular functions are regulated by enzymes that use NAD + not as a redox cofactor but as a substrate in a coupled reaction in which the availability of NAD + can be an indicator of the cell’s energy status.

A family of proteins called sirtuins regulate the activity of proteins in diverse cellular pathways by deacetylating the ε-amino group of an acetylated Lys residue. The deacetylation is coupled to NAD + hydrolysis, yielding O -acetyl-ADPribose and nicotinamide.

NAD + also plays an important role in cholera infections. Cholera toxin has an enzymatic activity that transfers ADP-ribose from NAD + to a G protein involved in regulating ion fluxes in the cells lining the gut. This ADP-ribosylation blocks water retention, causing the diarrhea and dehydration characteristic of cholera.

Both nicotinic acid and nicotinamide cure pellagra.