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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nicotinamide riboside kinases
Nicotinamide Mononucleotide
Assuming that NAADP+ is referred to (since the phosphate group is needed for stabilisation).
pre-cursor for serotonin/melatonin
in most cell types
Na phosphoribosyltransferase
3-hydroxyamino oxidase ( 3HAO )
Nam phosphoribosyltransferase
aka ADP ribose
N-ribosylnicotinamide = NR
occurs extracellularly in blood and milk and can be provided in the diet
aka glutamine-dependent NAD+ synthetase
most abundant kynurenines found in caput epididymal tissue
Provided by diet and, potentially, by bacterial degradative pathways in vertebrates
most abundant kynurenines found in caput epididymal tissue
in liver cells
formaminase (arylformamidase; AFMID )
kynurenine aminotransferase ( KAT ; also known as AADAT)
kynurenine 3-hydroxylase ( K3H ; also known as KMO)
kynureninase
phosphoribosyltransferase
kynureninase
indol derivative
nicotinamide riboside kinases
hydrolase in cytosol [PMID: 4400078]
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hydrolase in cytosol [PMID: 4400078]
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adenylylated
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aminotransferase in mitochondrial inner membrane [PMID: 4400078]
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adenylylated
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spontaneous condensation and rearrangement
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3-hydroxylase in mitochondrial outer membrane [PMID: 4400078]
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nicotinamide adenine dinucleotide biosynthetic pathway
PW:0000219
Pathway Ontology
nicotinamide adenine dinucleotide metabolic pathway
PW:0002580
Pathway Ontology
kynurenine metabolic pathway
PW:0001282
Pathway Ontology
de novo nicotinamide adenine dinucleotide biosynthetic pathway
PW:0001276
Pathway Ontology
nicotinamide adenine nucleotide utilization pathway
PW:0002581
Pathway Ontology
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway
PW:0001375
Pathway Ontology
tryptophan degradation pathway
PW:0001281
Pathway Ontology
21189261
PubMed
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PubMed
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4400078
PubMed
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