Scientific Reference
NAD+ (Nicotinamide Adenine Dinucleotide)
NAD+, or nicotinamide adenine dinucleotide, is present in every living cell and has been studied since it was found in yeast extracts over a hundred years ago, which makes it one of the oldest subjects in enzymology rather than a recent arrival. Structurally it is two nucleotides joined at their phosphates, one carrying adenine and the other nicotinamide, a form of vitamin B3; it is a coenzyme and contains no peptide. Mammalian cells can build it from tryptophan or nicotinic acid but mostly do not, relying instead on a salvage route that recycles nicotinamide at a rate set by the enzyme NAMPT. The current literature, largely rodent and cell culture, is less concerned with its metabolic role than with its signalling functions and with how its concentration shifts with age and metabolic state. What exogenous NAD+ does in humans remains thinly evidenced.
Mechanism of Action
The molecule does two unrelated jobs. The first is redox: it takes up a hydride ion to become NADH, and the NAD+/NADH couple ferries electrons from glycolysis and from mitochondrial dehydrogenases to complex I of the respiratory chain. The second is as a consumable substrate, and three enzyme families spend it — the sirtuins, which strip acetyl and other acyl groups off proteins; the PARPs, switched on by breaks in DNA strands; and CD38 and its relatives, which build signalling molecules such as cyclic ADP-ribose. A practical caveat attaches to anything given from outside: NAD+ in the extracellular space is generally understood to be cleaved by cell-surface enzymes into smaller precursors before uptake, so where exogenous NAD+ actually ends up is itself an open question.
Molecular Information
- Type: Coenzyme (dinucleotide)