NAD+ metabolism (Homo sapiens)

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NAD+ metabolism in different cellular compartments. The different precursors to intracellular NAD metabolism - tryptophan, nicotinic acid (NA), nicotinamide, NR, and NMN - are shown, along with their extra-cellular metabolism by CD38 and CD73. The cytoplasmic and nuclear NAD+ pools probably equilibrate by diffusion through the nuclear pore. However, the mitochondrial membrane is impermeable to both NAD+ and NADH. Reducing equivalents generated by glycolysis are transferred to the mitochondrial matrix via the malate/aspartate shuttle and the glyceraldehyde-3-phosphate shuttle. The resulting mitochondrial NADH (malate/aspartate shuttle) is oxidized by complex I in the respiratory chain (ETC), whereas the resulting FADH2 (glyceraldehyde-3-phosphate shuttle) is oxidized by complex II. In each of the three compartments, different NAD+-consuming enzymes lead to the generation of nicotinamide, which is recycled via the NAD+ salvage pathway. Different forms of the NMNAT enzyme and sirtuins are localized in different compartments. The nature of the salvage pathway for NAD+ in mitochondria has not been fully resolved, although NMNAT3 has been found in mitochondria. NADK, NAD+ kinase.

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Ontology Terms



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


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94904view23:25, 12 October 2017Khanspersadded lit ref
94795view23:19, 5 October 2017AlexanderPicoConnected interactions and fixed catalysis layouts
89859view12:26, 6 October 2016MkutmonModified description
88175view15:53, 29 July 2016JmeliusOntology Term : 'classic metabolic pathway' added !
85724view23:55, 6 June 2016Khansperslatest update
85610view22:57, 2 June 2016KhanspersQuick edit to datanode annotation or property
85549view23:48, 27 May 2016AlexanderPicoQuick edit to datanode annotation or property
85548view23:47, 27 May 2016AlexanderPicoQuick edit to datanode annotation or property
85541view22:43, 27 May 2016KhanspersModified description
85540view22:42, 27 May 2016KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
?NAMPTGeneProductENSG00000105835 (Ensembl)
?NMNAT3GeneProductENSG00000163864 (Ensembl)
CD38GeneProductENSG00000004468 (Ensembl)
CD73GeneProductENSG00000135318 (Ensembl)
FADH2MetaboliteHMDB01197 (HMDB)
FADHMetaboliteHMDB01197 (HMDB)


GlycolysisPathwayWP534 (WikiPathways)
L-Tryptophan (TRP)MetaboliteHMDB00929 (HMDB)
LactateMetaboliteHMDB00190 (HMDB)
Malate/aspartate shuttlePathway
NADHMetaboliteHMDB01487 (HMDB)
NADMetaboliteHMDB00902 (HMDB)
NADKGeneProductENSG00000008130 (Ensembl)
NADPHMetaboliteHMDB00221 (HMDB)
NADPMetaboliteHMDB00217 (HMDB)
NAMetaboliteHMDB01488 (HMDB)
NAMMetaboliteHMDB01406 (HMDB)
NAMNMetaboliteHMDB01132 (HMDB)
NAMPTGeneProductENSG00000105835 (Ensembl)
NMNMetabolite13553 (Chemspider)
NMNAT1GeneProductENSG00000173614 (Ensembl)
NMNAT2GeneProductENSG00000157064 (Ensembl)
NRMetaboliteHMDB00855 (HMDB)
NRKGeneProductENSG00000123572 (Ensembl)
Nicotinic acid (NA)MetaboliteHMDB01488 (HMDB)
PARP1GeneProductENSG00000143799 (Ensembl)
PRPPMetaboliteHMDB00280 (HMDB)
PyruvateMetaboliteHMDB00243 (HMDB)
SIRT1GeneProductENSG00000096717 (Ensembl)
SIRT2GeneProductENSG00000068903 (Ensembl)
SIRT3GeneProductENSG00000142082 (Ensembl)
SIRT4GeneProductENSG00000089163 (Ensembl)
SIRT5GeneProductENSG00000124523 (Ensembl)
SIRT6GeneProductENSG00000077463 (Ensembl)
SIRT7GeneProductENSG00000187531 (Ensembl)
TCA CyclePathwayWP73 (WikiPathways)
TRPMetaboliteHMDB00929 (HMDB)
dATPMetaboliteHMDB01532 (HMDB)

Annotated Interactions

No annotated interactions

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