Coenzyme reference
NAD+
Nicotinamide adenine dinucleotide · a central redox coenzyme and signalling substrate
Present in every living cell — it carries electrons through metabolism and is consumed as a substrate by enzymes that repair DNA and regulate ageing.
Formula
C21H27N7O14P2
Molecular weight
663.43 g/mol
Reduced form
NADH · 665.44 g/mol
Class
Dinucleotide coenzyme
How NAD+ is used
Two fundamentally different roles: recycled in redox reactions, consumed as a substrate in signalling.
Redox · recycled
Electron carrier
In redox reactions NAD+ cycles between NAD+ and NADH; the molecule is not destroyed.
- → Glycolysis (GAPDH step)
- → TCA cycle dehydrogenases
- → Oxidative phosphorylation, Complex I
- → Fatty acid oxidation
Signalling · consumed
Substrate cleavage
These enzymes cleave NAD+ and release nicotinamide, which must be salvaged back — turnover matters, not just pool size.
- ↯ Sirtuins (SIRT1–SIRT7) — deacetylation, releases nicotinamide
- ↯ PARPs (notably PARP1) — DNA damage response
- ↯ CD38 / CD157 — immune signalling; a major NAD+ consumer that rises with age
- ↯ SARM1 — axonal degeneration
Molecular architecture
NAD+ is a dinucleotide — two nucleotides bridged by a pyrophosphate. Click a segment to isolate it.
NAD+ (oxidised). Ready to accept a hydride ion at the nicotinamide ring. A related molecule, NADP+/NADPH, carries an extra phosphate on the adenosine ribose and is used for biosynthesis and antioxidant defence rather than energy production.
Composition breakdown
NAD+ contains 71 atoms across five structural components.
The business end — accepts and donates a hydride ion. This is where the redox chemistry happens, and it is the fragment released when NAD+ is cleaved by signalling enzymes.
Sugar backbone linking nicotinamide to the phosphate bridge.
Two phosphate groups joining the two halves of the molecule.
Sugar backbone on the adenosine half.
Recognition handle — how enzymes grip and orient the coenzyme.
Biosynthesis pathways
Three lanes converge on the cellular NAD+ pool. The salvage pathway supplies the majority of NAD+ in most tissues; NAMPT is the rate-limiting enzyme.
De novo pathway
- 01Tryptophan
- 02Kynurenine pathway
- 03Quinolinic acid
- 04NaMN
- 05NaAD
- 06NAD+
Preiss-Handler pathway
- 01Nicotinic acid (NA)
- 02NaMN
- 03NaAD
- 04NAD+
Salvage pathway
Dominant- 01Nicotinamide (NAM)
- 02NMN [via NAMPT · rate-limiting]
- 03NAD+ [via NMNAT]
Side entry: Nicotinamide riboside (NR) → NMN → NAD+ [via NRK].
Convergence
→ Cellular NAD+ pool ←
Decline and modulation
Reported declines in tissue NAD+ with age. Reported magnitudes vary substantially by tissue and by measurement method — treat this as a schematic trend, not measured values.
Nicotinamide riboside (NR)
Raises blood NAD+ in human trials; downstream clinical outcome data remains limited.
Nicotinamide mononucleotide (NMN)
Raises NAD+ in rodents; human trials exist but are small and short.
Niacin / nicotinic acid
Established vitamin B3, long clinical history, causes flushing at higher intakes.
Nicotinamide (NAM)
Established vitamin form.
Tryptophan
Dietary precursor via the de novo pathway; conversion is inefficient.
IV NAD+ infusion
Direct administration; poorly characterised pharmacology and no approved therapeutic indication.
Research & regulatory status
NAD+ itself is a normal metabolite.
Not a drug — every cell makes it. The regulatory questions concern supplementation and administration, not the molecule's existence.
Vitamin B3 forms are food substances.
Niacin and nicotinamide are established vitamins with defined intake recommendations.
NMN's US status is contested.
In 2022 the FDA took the position that NMN is excluded from the dietary supplement definition on the grounds that it had been authorised for investigation as a new drug — a position that has been disputed by industry. Verify current status.
IV NAD+ therapy is not approved.
Offered in clinics but holds no marketing authorisation for any indication in the US, UK or EU.
Much of the excitement around NAD+ rests on rodent longevity and metabolic work. Human trials consistently show precursors raise blood NAD+; they have been much less consistent in showing that this produces meaningful clinical benefit.