Kynurenine aminotransferase 3/glutamine transaminase L/cysteine conjugate beta-lyase 2 is a major glutamine transaminase in the mouse kidney

Abstract

BackgroundKynurenine aminotransferase 3 (KAT3) catalyzes the transamination of Kynurenine to kynurenic acid, and is identical to cysteine conjugate beta-lyase 2 (CCBL2) and glutamine transaminase L (GTL). GTL was previously purified from the rat liver and considered as a liver type glutamine transaminase. However, because of the substrate overlap and high sequence similarity of KAT3 and KAT1, it was difficult to assay the specific activity of each KAT and to study the enzyme localization in animals.MethodsKAT3 transcript and protein levels as well as enzyme activity in the liver and kidney were analyzed by regular reverse transcription-polymerase chain reaction (RT-PCR), real time RT-PCR, biochemical activity assays combined with a specific inhibition assay, and western blotting using a purified and a highly specific antibody, respectively.ResultsThis study concerns the comparative biochemical characterization and localization of KAT 3 in the mouse. The results showed that KAT3 was present in both liver and kidney of the mouse, but was much more abundant in the kidney than in the liver. The mouse KAT3 is more efficient in transamination of glutamine with indo-3-pyruvate or oxaloacetate as amino group acceptor than the mouse KAT1.ConclusionsMouse KAT3 is a major glutamine transaminase in the kidney although it was named a liver type transaminase.General significanceOur data highlights KAT3 as a key enzyme for studying the nephrotoxic mechanism of some xenobiotics and the formation of chemopreventive compounds in the mouse kidney. This suggests tissue localizations of KAT3/GTL/CCBL2 in other animals may be carefully checked.

Kynurenic Acid Acts as a Signaling Molecule Regulating Energy Expenditure and Is Closely Associated With Metabolic Diseases

“…Likewise, KYAT3 is a multifunctional aminotransferase and catalyzes glutamine, methionine, phenylalanine, tyrosine and cysteine as transamination subtract, although it displayed no activity toward leucine ( 31 ). Its expression is much higher in kidney, liver and neuroendocrine tissues than in brain ( 27 , 32 ).…”

Upregulation of the Glutaminase II Pathway Contributes to Glutamate Production upon Glutaminase 1 Inhibition in Pancreatic Cancer

“…The formation of 13 C 5 ‐glutamate is explained through the transamination of α‐ketoglutarate derived from the glutaminase II pathway (Figure C, purple arrow; Equations (1) and (2)), into 13 C 5 ‐glutamate. The glutaminase II pathway consists of the glutamine transaminase K (GTK) (or kynurenine aminotransferase I) catalyzed conversion of glutamine to α‐ketoglutaramate (KGM) using a suitable α‐keto acid acceptor (Equation (1)) followed by hydrolysis of KGM to α‐ketoglutarate catalyzed by ω‐amidodicarboxylate amidohydrolase (ω‐amidase) (Equation (2)). This pathway can then act as a source of glutamate via transamination of α‐ketoglutarate by an α‐ketoglutarate‐linked aminotransferase (Equation (3)) or by reductive amination catalyzed by glutamate dehydrogenase (GDH) (Figure C, orange arrow).…”

Pyridoxal 5′-Phosphate-Dependent Enzymes at the Crossroads of Host–Microbe Tryptophan Metabolism

“…KAT III is also known as glutamine transaminase and has only recently been included among KAT isoenzymes [ 97 ]. It shows cysteine conjugate β-lyase activity and is abundantly expressed in the kidney and liver [ 98 ]. KAT IV is the most conserved isoenzyme, active toward a plethora of amino and keto acids [ 99 ].…”