Tryptophan catabolism leading to NAD+ production (Homo sapiens)
From WikiPathways
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
- 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 Scholia
- Belenky P, Bogan KL, Brenner C; ''NAD+ metabolism in health and disease.''; Trends Biochem Sci, 2007 PubMed Europe PMC Scholia
- 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 Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
2-Amino-3-carboxymuconate semialdehyde | Metabolite | 5280673 (PubChem-compound) | |
3-HAO | Protein | P46952 (Uniprot-TrEMBL) | 3-hydroxyamino oxidase ( 3HAO ) |
3-OH anthranilic acid (HAA) | Metabolite | Q2823213 (Wikidata) | |
3-OH kynurenine (HK) | Metabolite | Q2815992 (Wikidata) | |
3-hydroxyanthranilate dioxygenase | Protein | P46952 (Uniprot-TrEMBL) | |
5-HT | Metabolite | Q167934 (Wikidata) | pre-cursor for serotonin/melatonin |
ADP-ribosyl | Metabolite | Q27074316 (Wikidata) | aka ADP ribose |
AFMID | Protein | Q63HM1 (Uniprot-TrEMBL) | formaminase (arylformamidase; AFMID ) |
Anthranilic acid (AA) | Metabolite | Q385140 (Wikidata) | |
IDO | Protein | P14902 (Uniprot-TrEMBL) | in most cell types |
Indoxyl acetic acid (IAA) | Metabolite | Q411208 (Wikidata) | indol derivative |
K3H | Protein | O15229 (Uniprot-TrEMBL) | kynurenine 3-hydroxylase ( K3H ; also known as KMO) |
KAT | Protein | Q8N5Z0 (Uniprot-TrEMBL) | kynurenine aminotransferase ( KAT ; also known as AADAT) |
KYNU | Protein | Q16719 (Uniprot-TrEMBL) | kynureninase |
Kynurenic acid (KA) | Metabolite | Q642217 (Wikidata) | most abundant kynurenines found in caput epididymal tissue |
L-alanine | Metabolite | Q218642 (Wikidata) | |
L-kynurenine | Metabolite | Q415768 (Wikidata) | most abundant kynurenines found in caput epididymal tissue |
N-formyl kynurenine | Metabolite | Q27104120 (Wikidata) | |
N-methylnicotinamide | Metabolite | Q27088080 (Wikidata) | |
NAD+-consuming enzymes | Protein | ||
NAD+ | Metabolite | Q28775 (Wikidata) | |
NMN | Metabolite | Q27094156 (Wikidata) | Nicotinamide Mononucleotide |
NR | Metabolite | Q3334152 (Wikidata) |
|
Nadsyn1 | Protein | Q6IA69 (Uniprot-TrEMBL) | aka glutamine-dependent NAD+ synthetase |
Nam | Metabolite | Q192423 (Wikidata) | |
Naprt | Protein | Q6XQN6 (Uniprot-TrEMBL) | Na phosphoribosyltransferase |
Nicotinamide | Metabolite | Q192423 (Wikidata) | |
Nicotinic acid mononucleotide | Metabolite | CHEBI:37008 (ChEBI) | |
Nicotinic acid (NA) | Metabolite | Q11324215 (Wikidata) | Provided by diet and, potentially, by bacterial degradative pathways in vertebrates |
Nicotinic acid adenine dinucleotide (NaAD+) | Metabolite | Q905651 (Wikidata) | Assuming that NAADP+ is referred to (since the phosphate group is needed for stabilisation). |
Nicotinuric acid | Metabolite | Q27107528 (Wikidata) | |
Nmnat1 | Protein | Q9HAN9 (Uniprot-TrEMBL) | |
Nmnat2 | Protein | Q9BZQ4 (Uniprot-TrEMBL) | |
Nmnat3 | Protein | Q96T66 (Uniprot-TrEMBL) | |
Nrk1 | Protein | Q9NWW6 (Uniprot-TrEMBL) | nicotinamide riboside kinases |
Nrk2 | Protein | Q9NPI5 (Uniprot-TrEMBL) | nicotinamide riboside kinases |
PBEF | Protein | P43490 (Uniprot-TrEMBL) | Nam phosphoribosyltransferase |
QPRT | Protein | Q15274 (Uniprot-TrEMBL) | phosphoribosyltransferase |
Quinolinic acid (QA) | Metabolite | Q411945 (Wikidata) | |
Serotonin/melatonin production | Pathway | WP3298 (WikiPathways) | |
TDO | Protein | P48775 (Uniprot-TrEMBL) | in liver cells |
Tryptophan (Trp) | Metabolite | Q181003 (Wikidata) | |
Xanthurenic acid (XA) | Metabolite | Q5961262 (Wikidata) | |
protein synthesis | Pathway |
Annotated Interactions
No annotated interactions