Vitamin B3 (Niacin, Nicotinamid): the pathway in the body

Vitamin B3 (Niacin, Nicotinamid) is part of the pathway “NAD⁺”. This page shows the whole pathway; the station of Vitamin B3 (Niacin, Nicotinamid) is highlighted.

Where this laboratory value sits: Nicotinic acid — a form of vitamin B3. Nicotinic acid is one of the forms of vitamin B3 from food. The enzyme NAPRT attaches it to the sugar building block PRPP, forming the same NaMN that stands at the end of the kynurenine pathway. It spares the long route from tryptophan. Source 7, 2

In brief

NAD⁺ (nicotinamide adenine dinucleotide) is a coenzyme that the body forms from tryptophan or from forms of vitamin B3. It transfers hydrogen in many metabolic reactions and serves enzymes such as sirtuins and PARP as a substrate. In doing so it is split.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Tryptophan → Quinolinic acid Kynurenine pathway · Haem iron, Vitamin B6 Quinolinic acid forms over several steps of the kynurenine pathway. The first step opens the ring of tryptophan; the enzyme for this carries haem iron, and a later step needs vitamin B6. At the NMDA receptor it also has an excitatory effect. Source 3↕ both, depending on amount Quinolinic acid is the building block that QPRT carries on towards NAD⁺. At the NMDA receptor of nerve cells it also has an excitatory effect; which side prevails depends on how quickly QPRT removes it. observed in studies Source 3
   ⚖ When the balance tips

   too much — If quinolinic acid builds up because QPRT cannot keep pace, more of it remains at the NMDA receptor; in cell culture and animal models this strains the nerve cells.

   too little — If little quinolinic acid forms, the route from tryptophan contributes hardly anything to NAD⁺; the supply then comes from nicotinic acid, nicotinamide and recycling.

   observed in studies · Source 3

2. Quinolinic acid → NaMN QPRT Both routes meet here: QPRT attaches quinolinic acid to the sugar building block PRPP and splits off carbon dioxide, NAPRT does the same with nicotinic acid. Nicotinic acid mononucleotide (NaMN) is formed. From here both routes share the same steps. Source 2, 7↑ supplies NaMN is the meeting point of two routes: quinolinic acid from tryptophan and nicotinic acid from food flow in here. From here on they share the same steps up to NAD⁺. established physiology Source 2, 7
   ⚖ When the balance tips

   too much — If much NaMN forms, the NMNAT enzymes and NAD synthetase that follow set the pace, not the supply of precursors.

   too little — If little NaMN forms, this route contributes less to NAD⁺, and the supply relies more on recycling via NAMPT.

   established physiology · Source 2, 7

3. Nicotinic acid → NaMN NAPRT Both routes meet here: QPRT attaches quinolinic acid to the sugar building block PRPP and splits off carbon dioxide, NAPRT does the same with nicotinic acid. Nicotinic acid mononucleotide (NaMN) is formed. From here both routes share the same steps. Source 2, 7↑ supplies NaMN is the meeting point of two routes: quinolinic acid from tryptophan and nicotinic acid from food flow in here. From here on they share the same steps up to NAD⁺. established physiology Source 2, 7
   ⚖ When the balance tips

   too much — If much NaMN forms, the NMNAT enzymes and NAD synthetase that follow set the pace, not the supply of precursors.

   too little — If little NaMN forms, this route contributes less to NAD⁺, and the supply relies more on recycling via NAMPT.

   established physiology · Source 2, 7

4. NaMN → NaAD NMNAT1-3 · ATP Enzymes of the NMNAT family attach an adenine unit from ATP to NaMN. They work in the nucleus, the cytoplasm and the mitochondrion. Each part of the cell thus forms its own pool. Source 2↑ supplies NaAD is the precursor that lacks only the amide group. Because the NMNAT enzymes sit in the nucleus, the cytoplasm and the mitochondrion, each part of the cell can form its own NAD⁺ pool. established physiology Source 2
   ⚖ When the balance tips

   too much — If much NaAD is present, NAD synthetase sets the limit; it needs glutamine and ATP for each conversion.

   too little — If little NaAD forms, for example because little ATP is available, NAD synthetase receives less material, and less NAD⁺ forms by this route.

   established physiology · Source 2

5. NaAD → NAD⁺ NAD synthetase · ATP NAD synthetase swaps the acid group for an amide group from glutamine. NAD⁺ is then complete. It serves as a hydrogen carrier and is split by sirtuins, PARP and CD38. Source 2↑ supplies Finished NAD⁺ has two tasks: it transfers hydrogen in energy metabolism and serves sirtuins, PARP and CD38 as a substrate, which split it in the process. Both tasks draw on the same pool. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — NAD⁺ does not accumulate without limit: part of it is converted to NADP⁺, part is continuously split by sirtuins, PARP and CD38, and plenty of NAD⁺ slows the enzyme NAMPT.

   too little — If little NAD⁺ is available, energy metabolism and the splitting enzymes draw on the same molecules; sirtuins then work more slowly, because they bind NAD⁺ less tightly than PARP.

   established physiology · Source 1, 2

6. NMN → NAD⁺ NMNAT1-3 · ATP NAD synthetase swaps the acid group for an amide group from glutamine. NAD⁺ is then complete. It serves as a hydrogen carrier and is split by sirtuins, PARP and CD38. Source 2↑ supplies Finished NAD⁺ has two tasks: it transfers hydrogen in energy metabolism and serves sirtuins, PARP and CD38 as a substrate, which split it in the process. Both tasks draw on the same pool. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — NAD⁺ does not accumulate without limit: part of it is converted to NADP⁺, part is continuously split by sirtuins, PARP and CD38, and plenty of NAD⁺ slows the enzyme NAMPT.

   too little — If little NAD⁺ is available, energy metabolism and the splitting enzymes draw on the same molecules; sirtuins then work more slowly, because they bind NAD⁺ less tightly than PARP.

   established physiology · Source 1, 2

7. NAD⁺ in metabolism → NADH Dehydrogenases In glycolysis, fatty acid breakdown and the citric acid cycle, dehydrogenases remove hydrogen from nutrients and transfer it to NAD⁺. This produces NADH. NADH carries the electrons to the respiratory chain. Source 1↑ supplies NADH is the loaded carrier: it brings electrons from glycolysis, fatty acid breakdown and the citric acid cycle to the respiratory chain, where ATP is formed from them. Only once it has handed them over is NAD⁺ available again. established physiology Source 1
   ⚖ When the balance tips

   too much — If NADH builds up, for example when the respiratory chain cannot keep pace, the dehydrogenases slow down because they are missing NAD⁺ as an acceptor.

   too little — If little NADH forms, fewer electrons reach complex I, and less ATP is made in the respiratory chain.

   established physiology · Source 1

8. NADH → Respiratory chain Complex I NADH passes its electrons to complex I of the respiratory chain. This produces ATP, and NAD⁺ becomes available again. It thus keeps the ratio of NAD⁺ to NADH in balance. Source 1↑ supplies The respiratory chain returns NAD⁺ and gains energy in the process: complex I removes the electrons from NADH and pumps protons, whose gradient drives ATP synthase. established physiology Source 1
   ⚖ When the balance tips

   too much — If the respiratory chain works briskly, NADH is quickly converted back to NAD⁺, and the ratio shifts towards the unloaded form.

   too little — If the respiratory chain works more slowly, more NADH stays loaded, NAD⁺ becomes scarcer, and the dehydrogenases upstream slow down.

   established physiology · Source 1

9. NAD⁺ in metabolism → Nicotinamide Sirtuins, PARP, CD38 Sirtuins, PARP and CD38 really split NAD⁺: sirtuins remove acetyl groups from proteins, PARP works at DNA breaks, CD38 breaks NAD⁺ down. Nicotinamide is left each time; it also comes from food. NAMPT recovers it. Source 1, 2↓ depletes Here NAD⁺ is used up, not just reloaded: sirtuins, PARP and CD38 split it and release nicotinamide. The harder they work, the more NAD⁺ has to be remade via NAMPT. established physiology Source 1, 2
   ⚖ When the balance tips

   too much — If PARP or CD38 work hard, for example with many DNA breaks or in immune cells, NAD⁺ is split faster than NAMPT can remake it, and the pool falls.

   too little — If the splitting enzymes are not very active, more NAD⁺ is retained; at the same time sirtuins remove fewer acetyl groups from proteins, and PARP marks DNA breaks less often.

   established physiology · Source 2, 1

10. NAD⁺ in metabolism → NADP⁺ NAD kinase · ATP NAD kinase attaches a phosphate group to NAD⁺. NADP⁺ and its loaded form NADPH are kept separately and serve to build fats and to handle reactive oxygen species. NADPH also regenerates glutathione. Source 4↑ supplies NAD kinase is the only source of new NADP⁺. As NADPH it supplies the electrons for building fats and for regenerating glutathione, which traps reactive oxygen species. established physiology Source 4
    ⚖ When the balance tips

    too much — If much NAD⁺ is converted to NADP⁺, this share is no longer available to energy metabolism.

    too little — If NAD kinase is not very active, less NADP⁺ forms; fewer electrons are then available for building fats and regenerating glutathione.

    established physiology · Source 4

11. Nicotinamide → NMN NAMPT · PRPP The short route: the enzyme NAMPT attaches nicotinamide to PRPP, forming NMN. Most of the NAD⁺ supply comes from this recycling route. NAMPT is the slowest step. Source 1, 2↑ supplies Via NMN the cell recovers the nicotinamide that is left over each time NAD⁺ is split. This cycle carries most of the supply; NAMPT is its slowest step. established physiology Source 1, 2
    ⚖ When the balance tips

    too much — If plenty of NAD⁺ is present, it slows NAMPT; the cell then makes less NMN than it could.

    too little — If NAMPT works more slowly, less NMN forms, and less nicotinamide from split NAD⁺ is recovered; if splitting continues, the NAD⁺ pool falls.

    established physiology · Source 1, 2

Further stations

• Tryptophan — Amino acid from food Tryptophan is an amino acid from dietary protein. A small part of it enters the kynurenine pathway, at the end of which lies a building block for NAD⁺. The same pool also serves protein synthesis and serotonin formation. Source 3↑ supplies Tryptophan supplies a building block for NAD⁺ via the long kynurenine pathway. The same pool also serves protein synthesis and serotonin formation; if one route is used more, less remains for the others. established physiology Source 3
  ⚖ When the balance tips

  too much — If more tryptophan arrives, more of it runs via the enzyme TDO in the liver into the kynurenine pathway; TDO is itself stimulated by its substrate.

  too little — If little tryptophan arrives, the long route contributes hardly anything to NAD⁺; the supply then depends on nicotinic acid, nicotinamide and recycling.

  established physiology · Source 3, 7

• NAD⁺ in metabolism — Hydrogen carrier In many reactions NAD⁺ accepts hydrogen and releases it again elsewhere. It is not used up in the process but shuttles between two forms. The ratio of NAD⁺ to NADH determines how briskly dehydrogenases work. Source 1↑ supplies The ratio of NAD⁺ to NADH determines how easily dehydrogenases can remove hydrogen: if much NAD⁺ is present, glycolysis and the citric acid cycle run briskly. The respiratory chain keeps this ratio in balance. established physiology Source 1
  ⚖ When the balance tips

  too much — If there is much NAD⁺ and little NADH, the dehydrogenases find plenty of acceptors for hydrogen; the pace is then set by nutrient supply and demand for ATP.

  too little — If there is little NAD⁺ relative to NADH, the dehydrogenases slow down; in glycolysis more pyruvate is then converted to lactate, which recovers NAD⁺.

  established physiology · Source 1

• Nicotinic acid — a form of vitamin B3 Nicotinic acid is one of the forms of vitamin B3 from food. The enzyme NAPRT attaches it to the sugar building block PRPP, forming the same NaMN that stands at the end of the kynurenine pathway. It spares the long route from tryptophan. Source 7, 2↑ supplies Nicotinic acid supplies NAD⁺ by its own route via NAPRT, independently of recycling via NAMPT. It spares the body the long route from tryptophan. established physiology Source 7, 2
  ⚖ When the balance tips

  too much — If much nicotinic acid arrives, it widens the blood vessels of the skin via its own receptor; this produces the well-known flush.

  too little — If little nicotinic acid arrives, NAD⁺ comes more from nicotinamide, from recycling and from tryptophan.

  established physiology · Source 7

Cofactors in this pathway

• Niacin (vitamin B3) — Nicotinic acid and nicotinamide are precursors from which the cell builds NAD⁺; they spare the long tryptophan route Source 1, 2
• Tryptophan — Starting material of the kynurenine pathway, which ends in quinolinic acid for NAD⁺; the route to NAD⁺ has many steps Source 3In the ORY catalogue as a laboratory value: Tryptophan
• Vitamin B6 — As pyridoxal phosphate, cofactor of a step in the kynurenine pathway; with little of it, the route stalls Source 3In the ORY catalogue as a laboratory value: Vitamin B6
• Iron — As haem iron, cofactor of the enzyme that opens the tryptophan ring; this starts the long route Source 3In the ORY catalogue as a laboratory value: Eisen
• Glutamine — Provides NAD synthetase with the amide group; this completes NAD⁺ Source 2In the ORY catalogue as a laboratory value: Glutamin
• Magnesium — Forms the complex with ATP that NMNAT and NAD kinase act on; without it neither step runs Source 5, 2In the ORY catalogue as a laboratory value: Magnesium
• PRPP — Supplies NAPRT, NAMPT and QPRT with the sugar-phosphate part of the molecule and is needed by all three routes Source 2

What acts on this pathway

• Inflammatory signals — Interferon-γ, TNF and bacterial LPS make many cells form more of the enzyme IDO. More tryptophan then runs into the kynurenine pathway, at whose end this route begins. Source 6, 3

Sources

1. Covarrubias AJ, Perrone R et al. NAD(+) metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 2021 · PubMed 33353981
2. Chini CCS, Zeidler JD et al. Evolving concepts in NAD(+) metabolism. Cell Metab 2021 · PubMed 33930322
3. Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res 2017 · PubMed 28469468
4. Oka SI, Titus AS et al. Molecular properties and regulation of NAD(+) kinase (NADK). Redox Biol 2023 · PubMed 36512915
5. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev 2015 · PubMed 25540137
6. Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 2013 · PubMed 23103127
7. Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr 2008 · PubMed 18429699

Whole pathway: NAD⁺

Related pathways

• Kynurenine pathway — tryptophan
• Protein fermentation in the colon — tryptophan
• Lactate and pyruvate — respiratory chain
• Serotonin and melatonin — tryptophan
• Dopamine, noradrenaline, adrenaline — Vitamin B6, Eisen

As of 2026-10-01. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending. Extended on 1 October 2026 with the route from nicotinic acid and the inflammation axis; two drawing faults fixed along the way.
Legal notice Privacy policy All biomarkers