Generally KP is a major degradative pathway that occurs in the liver, which synthesizes NAD+ from tryptophan (TRP). TRP acts as a precursor, in the central nervous system to several metabolic pathways, such as synthesis of kynurenine (KYN), serotonin, melatonin (Ruddick et al., 2006). The rate-limiting step in KP is the indole ring opening which is catalysed either by indoleamine-2,3-dioxygenases (IDO-1) or tryptophan 2,3-dioxygenase (TDO). The expression of IDO-1 and TDO is observed in different tissues and they are exposed to different stimuli, proposing that they have distinct functions in health and disease. The enzymes of KP are produced in many cell types and tissues which were significantly seen with the abundance of subsequent metabolites such as NAD+ and its reduced forms NADH (reduced nicotinamide adenine dinucleotide (phosphate)), pellagra-preventing factor, niacin or vitamin B3, PA (picolinic acid), NMDA (N-methyl-D-aspartate) receptor agonist QUIN (quinolinic acid) and antagonist KYNA (kynurenic acid), 3-HK (3-hydroxykynurenine) and 3-HAA (3-hydroxyanthranilic acid) (Badawy., 2017). TRP is converted to N′-formylkynurenine (NFK) either by TDO in liver or by IDO-1 extrahepatically. KYN is synthesized from NFK by the enzyme NFK formamidase (FAM). In the pathway, catalytic activity showing hydroxylation of KYN to 3-HK by KYN hydroxylase (KMO) followed by 3-HK hydrolysis to 3-HAA by kynureninase is noted. Kynureninase can also hydrolyze KYN to anthranilic acid (AA) while kynurenine aminotransferases (I, II, III) (KATs) desaminate KYN to KYNA (Sas et al., 2018). In the main catabolic pathway, along with 3-HAA, 2-amino-3-carboxymuconoate semialdehyde is produced. This semialdehyde latter process to form QUIN or decarboxylated to PA. QUIN is further metabolised by quinolinic acid phosphoribosyl transferase (QPRT) to niacin and consequently to NAD+ (Sas et al., 2018)

tryptophan metabolism References