NAD+ / NADP+ are the major cellular hydride acceptors — used by hundreds of dehydrogenases plus sirtuins (NAD+-consuming deacetylases) plus PARPs (NAD+-consuming DNA repair). Sources: (1) De novo from tryptophan via the kynurenine pathway (see tryptophan_metabolism) — quinolinic acid → NAD+ via QPRT. (2) Preformed from dietary niacin (nicotinic acid / nicotinamide / nicotinamide riboside) via the Preiss-Handler pathway. ~60 mg dietary tryptophan = 1 mg niacin equivalent. Pellagra (niacin deficiency) presents as the 4 D's: dermatitis, diarrhea, dementia, death — historically endemic in corn-dependent populations because corn niacin is bound and bioavailability is low. NAD+ supplementation (NR, NMN, NAD+ precursors) is heavily promoted for longevity but rigorous evidence remains thin.
Organ Systems
endocrine
nervous
Pathway Steps
tryptophan → quinolinic-acid — via kynurenine pathway (TDO/IDO → KMO → 3-OH-anthranilate → QA). The de-novo route makes NAD from tryptophan via the kynurenine pathway (TDO/IDO-initiated); ~60 mg tryptophan substitutes for ~1 mg niacin. Its intermediate quinolinic acid is also an NMDA-receptor excitotoxin, linking NAD synthesis to neuroinflammation.
quinolinic-acid → nicotinic-acid-mononucleotide — via QPRT (quinolinate phosphoribosyltransferase). Quinolinate phosphoribosyltransferase (QPRT) channels quinolinic acid into the NAD pool. B6 and riboflavin deficiencies upstream in the kynurenine pathway impair de-novo NAD synthesis and can precipitate pellagra despite adequate tryptophan.
nicotinic-acid → nicotinamide-adenine-dinucleotide — via Preiss-Handler pathway (NaPRT + NMNAT + glutamine-dependent NAD synthetase). The Preiss–Handler salvage builds NAD from dietary niacin via NaPRT → NMNAT → NAD synthetase. Pharmacologic nicotinic acid (but not nicotinamide) also lowers lipids and causes flushing via GPR109A — a role distinct from its vitamin function.
nr → nicotinamide-adenine-dinucleotide — via NRK (nicotinamide riboside kinase) + NMNAT — the NR-supplementation entry point. Nicotinamide riboside is salvaged via NRK → NMNAT (and NMN similarly) — the basis of NR/NMN “NAD-boosting” supplements that target the age-related decline in NAD⁺ and sirtuin activity.