Tryptophan catabolism leading to NAD+ production (Homo sapiens)

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1, 221, 321, 322121322121222221NMNNmnat1ADP-ribosylNrk1Tryptophan (Trp)Nadsyn1Nicotinic acid adenine dinucleotide (NaAD+)5-HT3-hydroxyanthranilate dioxygenasePBEFSerotonin/melatonin productionNR3-HAOL-alanineNAD+N-methylnicotinamide2-Amino-3-carboxymuconatesemialdehydeNAD+-consuming enzymesNicotinuric acidprotein synthesisNicotinic acid mononucleotideIDONaprtN-formyl kynurenineL-kynurenine3-OH kynurenine (HK)3-OH anthranilic acid (HAA)Quinolinic acid (QA)Nicotinic acid (NA)Nicotinamide11, 3111Kynurenic acid (KA)1Xanthurenic acid (XA)Anthranilic acid (AA)11TDOAFMIDKATK3HKYNUQPRTKYNUIndoxyl acetic acid (IAA)Nmnat2Nmnat3NamNrk2


Description

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.

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Ontology Terms

 

Bibliography

  1. Jrad-Lamine A, Henry-Berger J, Gourbeyre P, Damon-Soubeyrand C, Lenoir A, Combaret L, Saez F, Kocer A, Tone S, Fuchs D, Zhu W, Oefner PJ, Munn DH, Mellor AL, Gharbi N, Cadet R, Aitken RJ, Drevet JR; ''Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state.''; J Biol Chem, 2011 PubMed Europe PMC
  2. Belenky P, Bogan KL, Brenner C; ''NAD+ metabolism in health and disease.''; Trends Biochem Sci, 2007 PubMed Europe PMC
  3. Okamoto H, Okada F, Hayaishi O; ''Kynurenine metabolism in hyperthyroidism. A biochemical basis for the low NAD(P) level in hyperthyroid rat liver.''; J Biol Chem, 1971 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
95880view15:32, 31 January 2018DeSlIncluded info from ref 3 in PW
95879view15:22, 31 January 2018DeSlAdded ID for serotonin/melatonin production
95878view15:15, 31 January 2018DeSlAdded database for 3-hydroxyanthranilate dioxygenase
95877view15:12, 31 January 2018DeSlAdded ID for 3-hydroxyanthranilate dioxygenase
95876view15:08, 31 January 2018DeSlOntology Term : 'kynurenine metabolic pathway' added !
95875view15:08, 31 January 2018DeSlOntology Term : 'nicotinamide adenine nucleotide utilization pathway' added !
95874view15:08, 31 January 2018DeSlOntology Term : 'nicotinamide adenine dinucleotide metabolic pathway' added !
95873view15:08, 31 January 2018DeSlOntology Term : 'nicotinamide adenine dinucleotide biosynthetic pathway' added !
95872view15:08, 31 January 2018DeSlOntology Term : 'de novo nicotinamide adenine dinucleotide biosynthetic pathway' added !
95871view15:07, 31 January 2018DeSlOntology Term : 'nicotinamide adenine dinucleotide biosynthesis, the salvage pathway' added !
95870view15:07, 31 January 2018DeSlOntology Term : 'tryptophan degradation pathway' added !
95869view15:06, 31 January 2018DeSlAnnotated additional metabolites
95868view15:00, 31 January 2018DeSlModified description
95867view14:54, 31 January 2018DeSlNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2-Amino-3-carboxymuconate semialdehydeMetabolite5280673 (PubChem-compound)
3-HAOProteinP46952 (Uniprot-TrEMBL) 3-hydroxyamino oxidase ( 3HAO )
3-OH anthranilic acid (HAA)MetaboliteQ2823213 (Wikidata)
3-OH kynurenine (HK)MetaboliteQ2815992 (Wikidata)
3-hydroxyanthranilate dioxygenaseProteinP46952 (Uniprot-TrEMBL)
5-HTMetaboliteQ167934 (Wikidata) pre-cursor for serotonin/melatonin
ADP-ribosylMetaboliteQ27074316 (Wikidata) aka ADP ribose
AFMIDProteinQ63HM1 (Uniprot-TrEMBL) formaminase (arylformamidase; AFMID )
Anthranilic acid (AA)MetaboliteQ385140 (Wikidata)
IDOProteinP14902 (Uniprot-TrEMBL) in most cell types
Indoxyl acetic acid (IAA)MetaboliteQ411208 (Wikidata) indol derivative
K3HProteinO15229 (Uniprot-TrEMBL) kynurenine 3-hydroxylase ( K3H ; also known as KMO)
KATProteinQ8N5Z0 (Uniprot-TrEMBL) kynurenine aminotransferase ( KAT ; also known as AADAT)
KYNUProteinQ16719 (Uniprot-TrEMBL) kynureninase
Kynurenic acid (KA)MetaboliteQ642217 (Wikidata) most abundant kynurenines found in caput epididymal tissue
L-alanineMetaboliteQ218642 (Wikidata)
L-kynurenineMetaboliteQ415768 (Wikidata) most abundant kynurenines found in caput epididymal tissue
N-formyl kynurenineMetaboliteQ27104120 (Wikidata)
N-methylnicotinamideMetaboliteQ27088080 (Wikidata)
NAD+-consuming enzymesProtein
NAD+MetaboliteQ28775 (Wikidata)
NMNMetaboliteQ27094156 (Wikidata) Nicotinamide Mononucleotide
NRMetaboliteQ3334152 (Wikidata)
  • N-ribosylnicotinamide = NR
  • occurs extracellularly in blood and milk and can be provided in the diet
Nadsyn1ProteinQ6IA69 (Uniprot-TrEMBL) aka glutamine-dependent NAD+ synthetase
NamMetaboliteQ192423 (Wikidata)
NaprtProteinQ6XQN6 (Uniprot-TrEMBL) Na phosphoribosyltransferase
NicotinamideMetaboliteQ192423 (Wikidata)
Nicotinic acid mononucleotideMetaboliteCHEBI:37008 (ChEBI)
Nicotinic acid (NA)MetaboliteQ11324215 (Wikidata) Provided by diet and, potentially, by bacterial degradative pathways in vertebrates
Nicotinic acid adenine dinucleotide (NaAD+)MetaboliteQ905651 (Wikidata) Assuming that NAADP+ is referred to (since the phosphate group is needed for stabilisation).
Nicotinuric acidMetaboliteQ27107528 (Wikidata)
Nmnat1ProteinQ9HAN9 (Uniprot-TrEMBL)
Nmnat2ProteinQ9BZQ4 (Uniprot-TrEMBL)
Nmnat3ProteinQ96T66 (Uniprot-TrEMBL)
Nrk1ProteinQ9NWW6 (Uniprot-TrEMBL) nicotinamide riboside kinases
Nrk2ProteinQ9NPI5 (Uniprot-TrEMBL) nicotinamide riboside kinases
PBEFProteinP43490 (Uniprot-TrEMBL) Nam phosphoribosyltransferase
QPRTProteinQ15274 (Uniprot-TrEMBL) phosphoribosyltransferase
Quinolinic acid (QA)MetaboliteQ411945 (Wikidata)
Serotonin/melatonin productionPathwayWP3298 (WikiPathways)
TDOProteinP48775 (Uniprot-TrEMBL) in liver cells
Tryptophan (Trp)MetaboliteQ181003 (Wikidata)
Xanthurenic acid (XA)MetaboliteQ5961262 (Wikidata)
protein synthesisPathway

Annotated Interactions

No annotated interactions

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