NAD+ biosynthetic pathways (Homo sapiens)

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1, 2De novo biosynthesis pathwayDietPreiss-Handler pathwayNAD-consumingenzymesNicotinamideTDO2NMNAT1QPRTNicotinamide mononucleotideIDO1CD38NADHNicotinic acid adenine dinucleotideBST1L-KynurenineNicotinic acid mononucleotideSIRT1NAD3-HAAACMSDNicotinic acidPARP1NADSYN1NAMPTTCA cycleTryptophanNicotinamide ribosideN-FormylkinQuinolinic acidACMSSIRT2NAPRT1AMSDietDietNMNAT1DietSalvage pathwayPARP4PARP2TNKSTNKS2SIRT3SIRT4SIRT5SIRT6SIRT7SIRT7


NAD+ biosynthetic pathways. NAD+ levels are maintained by three independent pathways. First, the Preiss-Handler pathway uses dietary nicotinic acid and the enzyme nicotinic acid phosphoribosyltransferase (NAPRT) to generate NAMN, which is then transformed into NAAD by NAMN transferase (NMNAT). Three forms of this enzyme (NMNAT1, -2, and -3) have distinct subcellular localizations. The process is completed by the transformation of NAAD into NAD+ by NAD+ synthase (NADS). Second, the de novo synthesis pathway of NAD from tryptophan occurs through the kinurenine pathway (5). The first step in this pathway is the rate-limiting conversion of tryptophan to N-formylkinurenine (N-formylkin) by either IDO or TDO. Formylkinurenine is transformed into L-kinurenine (L-kin), 3-hydroxykinurenine, and 3-hydroxyanthranilic acid (3-HAA) and finally to ACMS. This compound can spontaneously condense and rearrange into quinolinic acid, which is transformed into NAMN, at which point it converges with the Preiss-Handler pathway. ACMS can also be decarboxylated into AMS by ACMS decarboxylase (ACMSD), leading to its oxidation into acetyl-CoA via the TCA cycle. Third, the NAD+ salvage pathway recycles the nicotinamide generated as a by-product of the enzymatic activities of NAD+-consuming enzymes: sirtuins, PARPs, and the cADPR synthases (CD38 and CD157). Initially, NAMPT recycles nicotinamide into NMN, which is then converted into NAD+ via the different NMNATs.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms



  1. 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 Europe PMC
  2. Verdin E; ''NAD⁺ in aging, metabolism, and neurodegeneration.''; Science, 2015 PubMed Europe PMC


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106653view21:16, 12 September 2019KhanspersModified description
106162view12:05, 16 August 2019MaintBotHMDB identifier normalization
105654view05:14, 10 August 2019KhanspersModified description
90261view23:11, 27 October 2016AlexanderPicoChanged areas to default background color
88176view15:56, 29 July 2016JmeliusOntology Term : 'classic metabolic pathway' added !
85725view00:58, 7 June 2016Khanspersincreased width of label
85723view23:47, 6 June 2016KhanspersModified description
85721view23:13, 6 June 2016KhanspersAdded rounded rectangle backgrounds
85609view22:54, 2 June 2016KhanspersAdded WPID for TCA cycle
85547view23:45, 27 May 2016AlexanderPicoUpdated layout and oxidation on NAD+
85546view23:32, 27 May 2016AlexanderPicoQuick edit to datanode annotation or property
85543view22:46, 27 May 2016KhanspersModified description
85542view22:45, 27 May 2016KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
3-HAAMetaboliteHMDB0001476 (HMDB)
ACMSDGeneProductENSG00000153086 (Ensembl)
ACMSMetaboliteHMDB0001330 (HMDB)
AMSMetaboliteHMDB0001330 (HMDB)
BST1GeneProductENSG00000109743 (Ensembl)
CD38GeneProductENSG00000004468 (Ensembl)
IDO1GeneProductENSG00000131203 (Ensembl)
L-KynurenineMetaboliteHMDB0000684 (HMDB)
N-FormylkinMetaboliteHMDB0001200 (HMDB)
NADHMetaboliteHMDB0001487 (HMDB)
NADMetaboliteHMDB0000902 (HMDB)
NADSYN1GeneProductENSG00000172890 (Ensembl)
NAMPTGeneProductENSG00000105835 (Ensembl)
NAPRT1GeneProductENSG00000147813 (Ensembl)
NMNAT1GeneProductENSG00000173614 (Ensembl)
Nicotinamide mononucleotideMetabolite13553 (Chemspider)
Nicotinamide ribosideMetaboliteHMDB0000855 (HMDB)
NicotinamideMetaboliteHMDB0001406 (HMDB)
Nicotinic acid adenine dinucleotideMetaboliteHMDB0001179 (HMDB)
Nicotinic acid mononucleotideMetaboliteHMDB0001132 (HMDB)
Nicotinic acidMetaboliteHMDB0001488 (HMDB)
PARP1GeneProductENSG00000143799 (Ensembl)
PARP2GeneProductENSG00000129484 (Ensembl)
PARP4GeneProductENSG00000102699 (Ensembl)
QPRTGeneProductENSG00000103485 (Ensembl)
Quinolinic acidMetaboliteHMDB0000232 (HMDB)
SIRT1GeneProductENSG00000096717 (Ensembl)
SIRT2GeneProductENSG00000068903 (Ensembl)
SIRT3GeneProductENSG00000142082 (Ensembl)
SIRT4GeneProductENSG00000089163 (Ensembl)
SIRT5GeneProductENSG00000124523 (Ensembl)
SIRT6GeneProductENSG00000077463 (Ensembl)
SIRT7GeneProductENSG00000187531 (Ensembl)
TCA cyclePathway
TDO2GeneProduct6999 (Entrez Gene)
TNKS2GeneProductENSG00000107854 (Ensembl)
TNKSGeneProductENSG00000173273 (Ensembl)
TryptophanMetaboliteHMDB0000929 (HMDB)

Annotated Interactions

No annotated interactions

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