Kynurenines with Neuroactive and Redox Properties: Relevance to Aging and Brain Diseases

Table 1

Kynurenine pathway enzymes and their positive and negative regulators.

Enzyme	Reaction catalyzed	Positive regulators	Negative regulators
Tryptophan 2,3-dioxygenase	L-Trp + O2/O2^•− → N-formyl-L-kynurenine	Melatonin, H2O2 [215].; O2^•− [216].	3-HK, KYNA, XA, NADH [217].; Cu^2+ [218].; Superoxide dismutase (SOD) [216].
Indolamine 2,3-dioxygenase	L-TRYP + O2/O2^•− → N-formyl-L-kynurenine	O2^•−; IFN-𝛼/𝛽/𝛾, lipopolysaccharide, hiperoxia [12, 219].	SOD [220].; NO [221].; H2O2, IL-4 [12].
Formamidase	N-formyl-L-kynurenine + H2O → formate + L-KYN	H2O, ascorbic acid, arginine, L-TRYP [222].	ANA [223].; 3-HK, Mn^2+ [222].
Kynureninase	L-KYN + H2O → ANA + L-alanine	H2O, 3-HK [224].
Kynurenine aminotransferases	L-KYN + 2-oxoglutarate/pyruvate → KYNA + L-glutamate	2-Oxoglutarato, pyruvate, 2-aminoadipate, pyridoxal 5′-phosphate [225, 226].	Glutamine, L-cysteine, 3-HK, L-phenylalanine, L-tryptophan, L-aspartate [191, 227–229].
Kynurenine 3-monooxygenase	L-KYN + NADPH + O2 → 3-HK	NADPH, O2, FAD, NADH, inflammatory stimulus [27, 230, 231].	ANA, XA, Cl^−, pyridoxal 5′-phosphate [28, 232].
3-Hydroxyanthranilic acid 3,4-dioxygenase	3-HA + O2 → 2-amino-3-carboxymuconate-6-semialdehyde	O2, Fe^2+ [233].	Zn^2+ [233].
2-Amino-3-carboxymuconate-6-semialdehyde decarboxylase	2-amino-3-carboxymuconate; -6-semialdehyde →; 2-aminomuconic-6-semialdehyde + CO2	KYNA, PIC, QUIN [234].	Zn^2+, Fe^2+ [234, 235].
Quinolinic acid phosphoribosyltransferase	QUIN + 5-phospho-𝛼-D-ribose 1-diphosphate → NAD^+ + diphosphate + CO2	Mg^2+[236, 237].	ATP, Cu^2+ Fe^2+, Fe^3+, Zn^2+ [238].