Tryptophan catabolism leading to NAD+ production (WP4210)

Homo sapiens

Scheme of mammalian tryptophan catabolism. Briefly, in mammalian cells, tryptophan is used mostly for protein synthesis. In a second quantitatively important pathway (driven by IDO in most cell types and by TDO more specifically in liver cells), it is the starting point of the kynurenine pathway. The kynurenine pathway gives birth to several metabolites, providing the appropriate enzymes that metabolize the various kynurenine intermediates are expressed. The main route of the kynurenine pathway leads to the formation of N -formyl kynurenine, L -kynurenine, 3-hydroxykynurenine, 3-hydroxyanthra- nilic acid, quinolinic acid, nicotinic acid, and in fine nicotinamine adenine dinucleotides. Additional lateral branches of the kynurenine pathway lead to the formation of other terminal kynurenines, such as KA, xanthurenic acid, and anthranilic acid. Kynurenines indicated in boldface type ( i.e. L -kynurenine and KA) correspond to the most abundant kynurenines found in caput epididymal tissue. Outside the kynurenine pathway, tryptophan is also the precursor of serotonin and melatonin. A very small proportion of tryptophan is also transformed into indol derivatives, such as indoxyl acetic acid. Conversion of Trp to N -formyl kynurenine is achieved via IDO and/or TDO. The kynurenine pathway can lead to the intracellular NAD+ production and consumption. De novo synthesis begins with the conversion of tryptophan to quinolate, which is converted to NaMN. NaMN is then adenylylated to form nicotinic acid adenine dinucleotide (NaAD+), which is converted to NAD+. NAD+-consuming enzymes break the bond between the Nam and ADP-ribosyl moieties. Nam, which is also provided in the diet, is salvaged to NMN, which is adenylylated to form NAD+. Na, which is provided in the diet and, potentially, by bacterial degradative pathways in vertebrates, is salvaged to form NaMN. NR, which occurs extracellularly in blood and milk and can be provided in the diet, is salvaged to NMN. Na and Nam are also converted to nicotinuric acid and N-methylnicotinamide elimination products.


Denise Slenter and Egon Willighagen


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Homo sapiens



Pathway Ontology

nicotinamide adenine dinucleotide biosynthetic pathway nicotinamide adenine dinucleotide metabolic pathway kynurenine metabolic pathway de novo nicotinamide adenine dinucleotide biosynthetic pathway nicotinamide adenine nucleotide utilization pathway nicotinamide adenine dinucleotide biosynthesis, the salvage pathway tryptophan degradation pathway


Label Type Compact URI Comment
Nicotinic acid mononucleotide Metabolite chebi:37008
NMN Metabolite wikidata:Q27094156 Nicotinamide Mononucleotide
NAD+ Metabolite wikidata:Q28775
Nicotinic acid adenine dinucleotide (NaAD+) Metabolite wikidata:Q905651 Assuming that NAADP+ is referred to (since the phosphate group is needed for stabilisation).
Nicotinuric acid Metabolite wikidata:Q27107528
5-HT Metabolite wikidata:Q167934 pre-cursor for serotonin/melatonin
N-methylnicotinamide Metabolite wikidata:Q27088080
Tryptophan (Trp) Metabolite wikidata:Q181003
L-alanine Metabolite wikidata:Q218642
2-Amino-3-carboxymuconatesemialdehyde Metabolite pubchem.compound:5280673
ADP-ribosyl Metabolite wikidata:Q27074316 aka ADP ribose
NR Metabolite wikidata:Q3334152 N-ribosylnicotinamide = NR
occurs extracellularly in blood and milk and can be provided in the diet
N-formyl kynurenine Metabolite wikidata:Q27104120
L-kynurenine Metabolite wikidata:Q415768 most abundant kynurenines found in caput epididymal tissue
3-OH kynurenine (HK) Metabolite wikidata:Q2815992
3-OH anthranilic acid (HAA) Metabolite wikidata:Q2823213
Quinolinic acid (QA) Metabolite wikidata:Q411945
Nicotinic acid (NA) Metabolite wikidata:Q11324215 Provided by diet and, potentially, by bacterial degradative pathways in vertebrates
Nicotinamide Metabolite wikidata:Q192423
Kynurenic acid (KA) Metabolite wikidata:Q642217 most abundant kynurenines found in caput epididymal tissue
Xanthurenic acid (XA) Metabolite wikidata:Q5961262
Anthranilic acid (AA) Metabolite wikidata:Q385140
Indoxyl acetic acid (IAA) Metabolite wikidata:Q411208 indol derivative
Nam Metabolite wikidata:Q192423
3-hydroxyanthranilate dioxygenase Protein uniprot:P46952
Nrk1 Protein uniprot:Q9NWW6 nicotinamide riboside kinases
IDO Protein uniprot:P14902 in most cell types
Naprt Protein uniprot:Q6XQN6 Na phosphoribosyltransferase
3-HAO Protein uniprot:P46952 3-hydroxyamino oxidase ( 3HAO )
PBEF Protein uniprot:P43490 Nam phosphoribosyltransferase
Nmnat1 Protein uniprot:Q9HAN9
Nadsyn1 Protein uniprot:Q6IA69 aka glutamine-dependent NAD+ synthetase
TDO Protein uniprot:P48775 in liver cells
AFMID Protein uniprot:Q63HM1 formaminase (arylformamidase; AFMID )
KAT Protein uniprot:Q8N5Z0 kynurenine aminotransferase ( KAT ; also known as AADAT)
K3H Protein uniprot:O15229 kynurenine 3-hydroxylase ( K3H ; also known as KMO)
KYNU Protein uniprot:Q16719 kynureninase
QPRT Protein uniprot:Q15274 phosphoribosyltransferase
KYNU Protein uniprot:Q16719 kynureninase
Nmnat2 Protein uniprot:Q9BZQ4
Nmnat3 Protein uniprot:Q96T66
Nrk2 Protein uniprot:Q9NPI5 nicotinamide riboside kinases


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