Target type: molecularfunction
Catalysis of the reaction: L-kynurenine + glyoxylate = 4-(2-aminophenyl)-2,4-dioxobutanoate + glycine. [EC:2.6.1.63, RHEA:19249]
Kynurenine-glyoxylate transaminase activity involves the transfer of an amino group from kynurenine to glyoxylate, resulting in the formation of kynurenic acid and glycine. This enzymatic activity is catalyzed by the enzyme kynurenine aminotransferase II (KAT II), which belongs to the class I pyridoxal phosphate-dependent aminotransferases. The reaction mechanism involves the initial binding of both kynurenine and glyoxylate to the active site of KAT II. Pyridoxal phosphate (PLP), a cofactor essential for the activity of KAT II, forms a Schiff base with the ε-amino group of a lysine residue in the active site. This Schiff base intermediate then interacts with the amino group of kynurenine, leading to the formation of a quinonoid intermediate. The quinonoid intermediate then reacts with glyoxylate, resulting in the transfer of the amino group from kynurenine to glyoxylate and the formation of kynurenic acid and glycine. The reaction is reversible, but under physiological conditions, the forward reaction is favored due to the high concentration of glyoxylate in the cell. Kynurenine-glyoxylate transaminase activity plays a crucial role in the metabolism of tryptophan, a precursor of kynurenine. Kynurenine is an intermediate in the kynurenine pathway, which is a major pathway for tryptophan degradation. Kynurenic acid, the product of kynurenine-glyoxylate transaminase activity, is a potent inhibitor of the NMDA receptor, a glutamate receptor involved in synaptic plasticity and neuronal excitability. Thus, kynurenine-glyoxylate transaminase activity can modulate neuronal activity by influencing the levels of kynurenic acid. Moreover, kynurenine-glyoxylate transaminase activity is implicated in various physiological and pathological processes, including neuroprotection, neurotoxicity, inflammation, and immune responses.'
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Protein | Definition | Taxonomy |
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Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial | A kynurenine/alpha-aminoadipate aminotransferase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N5Z0] | Homo sapiens (human) |
Kynurenine--oxoglutarate transaminase 3 | A kynurenine--oxoglutarate transaminase 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6YP21] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
pf-04859989 | PF-04859989: a potent, brain-penetrant inhibitor of kynurenine aminotransferase II/KAT II with in vivo activity; structure in first source |