NAD+ metabolism (WP3644)

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 electron transport chain, 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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3644 CPTAC Assay Portal]
last edited

Authors

Khanspers, AlexanderPico, Jmelius, Mkutmon, MaintBot, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: nicotinamide adenine dinucleotide metabolic pathway classic metabolic pathway

Participants

Label Type Compact Identifier
CD73 GeneProduct ensembl:ENSG00000135318
PRPP Metabolite hmdb:HMDB0000280
dATP Metabolite hmdb:HMDB0001532
L-Tryptophan Metabolite hmdb:HMDB0000929
ART GeneProduct None
NADK GeneProduct ensembl:ENSG00000008130
NMNAT1 GeneProduct ensembl:ENSG00000173614
NAMPT GeneProduct ensembl:ENSG00000105835
NADP Metabolite hmdb:HMDB0000217
Glycolysis Pathway wikipathways:WP534
Nicotinamide ribotide Metabolite chemspider:13553
NMNAT2 GeneProduct ensembl:ENSG00000157064
PARP1 GeneProduct ensembl:ENSG00000143799
NAD Metabolite hmdb:HMDB0000902
NMNAT3 GeneProduct ensembl:ENSG00000163864
FADH2 Metabolite hmdb:HMDB0001197
NADH Metabolite hmdb:HMDB0001487
Nicotinic acid mononucleotide Metabolite hmdb:HMDB0001132
TCA Cycle Pathway wikipathways:WP73
FADH Metabolite hmdb:HMDB0001197
Nicotinamide riboside Metabolite hmdb:HMDB0000855
Pyruvate Metabolite hmdb:HMDB0000243
NRK GeneProduct ensembl:ENSG00000123572
CD38 GeneProduct ensembl:ENSG00000004468
NAMPT GeneProduct ensembl:ENSG00000105835
Nicotinic acid Metabolite hmdb:HMDB0001488
L-Tryptophan Metabolite hmdb:HMDB0000929
Nicotinamide Metabolite hmdb:HMDB0001406
Nicotinamide Metabolite hmdb:HMDB0001488
Nicotinamide Metabolite hmdb:HMDB0001406
Nicotinamide riboside Metabolite hmdb:HMDB0000855
Nicotinamide Metabolite hmdb:HMDB0001406
NAD Metabolite hmdb:HMDB0000902
SIRT1 GeneProduct ensembl:ENSG00000096717
SIRT2 GeneProduct ensembl:ENSG00000068903
NADPH Metabolite hmdb:HMDB0000221
NAD Metabolite hmdb:HMDB0000902
NADH Metabolite hmdb:HMDB0001487
Nicotinamide Metabolite hmdb:HMDB0001406
Nicotinamide Metabolite hmdb:HMDB0001406
PARP1 GeneProduct ensembl:ENSG00000143799
NAMPT GeneProduct ensembl:ENSG00000105835
Nicotinamide ribotide Metabolite chemspider:13553
NAD Metabolite hmdb:HMDB0000902
SIRT1 GeneProduct ensembl:ENSG00000096717
SIRT2 GeneProduct ensembl:ENSG00000068903
SIRT5 GeneProduct ensembl:ENSG00000124523
SIRT6 GeneProduct ensembl:ENSG00000077463
SIRT7 GeneProduct ensembl:ENSG00000187531
NADH Metabolite hmdb:HMDB0001487
Nicotinamide Metabolite hmdb:HMDB0001406
NAD Metabolite hmdb:HMDB0000902
NADH Metabolite hmdb:HMDB0001487
Nicotinamide ribotide Metabolite chemspider:13553
NAD Metabolite hmdb:HMDB0000902
SIRT3 GeneProduct ensembl:ENSG00000142082
SIRT4 GeneProduct ensembl:ENSG00000089163
SIRT5 GeneProduct ensembl:ENSG00000124523
Nicotinamide mononucleotide Metabolite chemspider:13553
Lactate Metabolite hmdb:HMDB0000190
Glyceraldehyde3-phosphateshuttle Pathway None
Malate/aspartate shuttle Pathway None

References

  1. Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015 Dec 4;350(6265):1208–13. PubMed Europe PMC Scholia