NAD+ biosynthetic pathways (Homo sapiens)

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Description

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.

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Ontology Terms

 

Bibliography

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


History

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CompareRevisionActionTimeUserComment
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

Datanodes

View all...
NameTypeDatabase referenceComment
3-HAAMetaboliteHMDB01476 (HMDB)
ACMSDGeneProductENSG00000153086 (Ensembl)
ACMSMetaboliteHMDB01330 (HMDB)
AMSMetaboliteHMDB01330 (HMDB)
BST1GeneProductENSG00000109743 (Ensembl)
CD38GeneProductENSG00000004468 (Ensembl)
IDO1GeneProductENSG00000131203 (Ensembl)
L-KynurenineMetaboliteHMDB00684 (HMDB)
N-FormylkinMetaboliteHMDB01200 (HMDB)
NADHMetaboliteHMDB01487 (HMDB)
NADMetaboliteHMDB00902 (HMDB)
NADSYN1GeneProductENSG00000172890 (Ensembl)
NAMPTGeneProductENSG00000105835 (Ensembl)
NAPRT1GeneProductENSG00000147813 (Ensembl)
NMNAT1GeneProductENSG00000173614 (Ensembl)
Nicotinamide mononucleotideMetabolite13553 (Chemspider)
Nicotinamide ribosideMetaboliteHMDB00855 (HMDB)
NicotinamideMetaboliteHMDB01406 (HMDB)
Nicotinic acid adenine dinucleotideMetaboliteHMDB01179 (HMDB)
Nicotinic acid mononucleotideMetaboliteHMDB01132 (HMDB)
Nicotinic acidMetaboliteHMDB01488 (HMDB)
PARP1GeneProductENSG00000143799 (Ensembl)
PARP2GeneProductENSG00000129484 (Ensembl)
PARP4GeneProductENSG00000102699 (Ensembl)
QPRTGeneProductENSG00000103485 (Ensembl)
Quinolinic acidMetaboliteHMDB00232 (HMDB)
SIRT1GeneProductENSG00000096717 (Ensembl)
SIRT2GeneProductENSG00000068903 (Ensembl)
SIRT3GeneProductENSG00000142082 (Ensembl)
SIRT4GeneProductENSG00000089163 (Ensembl)
SIRT5GeneProductENSG00000124523 (Ensembl)
SIRT6GeneProductENSG00000077463 (Ensembl)
SIRT7GeneProductENSG00000187531 (Ensembl)
TCA cyclePathway
TDO2GeneProduct6999 (Entrez Gene)
TNKS2GeneProductENSG00000107854 (Ensembl)
TNKSGeneProductENSG00000173273 (Ensembl)
TryptophanMetaboliteHMDB00929 (HMDB)

Annotated Interactions

No annotated interactions

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