Briefly, through a series of enzymatic steps, tryptophan is normally converted into kynurenine, then to 3-hydroxykynurenine via kynurenine 3-monooxygenase (KMO; B2, NAD[P.sup.+]), then 3-hydroxyanthranilic acid is formed by kynureninase (KYNU; B6), and proceeds down the pathway to become either acetyl-coA, picolinic acid or quinolinic acid, which is further converted into NA[D.sup.+] through another series of enzymatic steps.
Kynureninase https://www.uniprot.org/uniprot/Q16719 Accessed 26 July 2018.
While IFN-[alpha]-stimulated BMM upregulated tryptophan 2,3-dioxygenase (TDO2) and KMO, stimulation of MDM was associated with the upregulation of KMO and kynureninase
Kynureninase, after it has been synthesized by IDO1, uses Kyn to generate anthranilic acid (AA) .
Botting, "Purification and biochemical characterization of some of the properties of recombinant human kynureninase," European Journal of Biochemistry, vol.
is a novel candidate gene for hypertension in spontaneously hypertensive rats.
Examples of B6 dependent enzymes are the aminotransferases, which are central in amino acid metabolism, and kynureninase
, which is required for the conversion of tryptophan to niacin.
The next step is the conversion of N-formylkynurenine to L-kynurenine (L-KYN), a metabolite that will serve as substrate for various enzymes: kynureninase which produces anthranilic acid (ANA), kynurenine aminotransferases (KAT I, II, and III), that catalyze the irreversible transamination from L-KYN to kynurenic acid (KYNA), and kynurenine 3-monooxygenase (KMO) that catalyzes the synthesis of 3-hydroxykynurenine (3-HK).
Kynureninase is a pyridoxal phosphate-dependent enzyme, which is mainly located in the cytosol and catalyses the transformation of KYN into ANA as well as of 3-HK to 3-HA.
Saran, "Properties and partial purification of kynureninase," The Biochemical Journal, vol.
Carpenedo, "Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities," Neuroscience, vol.
L-KYN is considered to be the end product of KYN pathway metabolism in most extrahepatic cells, whereas macrophages produce the largest amount of quinolinic acid (QUIN) in accordance with the highest activities of kynurenine 3-monooxygenase (KMO) and kynureninase