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. ed8 da4 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] e9c da4 ed8 ed8 da4 da4 hydrolase in cytosol [PMID: 4400078] ed8 e9c ed8 da4 da4 ed8 adenylylated da4 ed8 aminotransferase in mitochondrial inner membrane [PMID: 4400078] ed8 e9c da4 da4 da4 adenylylated da4 da4 spontaneous condensation and rearrangement da4 da4 ed8 3-hydroxylase in mitochondrial outer membrane [PMID: 4400078] ed8 e9c ed8 ed8 ed8 ed8 ed8 ed8 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 Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state. J Biol Chem 2011 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 17161604 PubMed NAD+ metabolism in health and disease. Trends Biochem Sci 2007 Belenky P Bogan KL Brenner C 4400078 PubMed Kynurenine metabolism in hyperthyroidism. A biochemical basis for the low NAD(P) level in hyperthyroid rat liver. J Biol Chem 1971 Okamoto H Okada F Hayaishi O