Kynurenine Aminotransferase III and Glutamine Transaminase L are Identical Enzymes that have Cysteine S-Conȷugate {beta}-Lyase Activity and can Transaminate L-Selenomethionine [Metabolism]
September 17th, 2014 by Pinto, J. T., Krasnikov, B. F., Alcutt, S., Jones, M. E., Dorai, T., Villar, M. T., Artigues, A., Li, J., Cooper, A. J. L.
Three of the four kynurenine aminotransferases (KAT I, II, and IV) that synthesize kynurenic acid, a neuromodulator, are identical to glutamine transaminase K (GTK), α-aminoadipate aminotransferase (AAT) and mitochondrial aspartate aminotransferase (AspAT), respectively. GTK/KAT I and AspAT/KAT IV possess cysteine S-conjugate β-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome databanks as CCBL1 (Cysteine Conjugate Beta-Lyase 1). Also listed, despite the fact that no β-lyase activity has been assigned to the encoded protein in the genome databank is a CCBL2 (synonym KAT III). We show that human KAT III/CCBL2 possesses cysteine S-conjugate β-lyase activity as does mouse KAT II. Thus, depending on the nature of the substrate, all four KATs possess cysteine S-conjugate β-lyase activity. These present studies show that KAT III and glutamine transaminase L (GTL) are identical enzymes. This report also shows that KAT I, II and III differ in their ability to transaminate methyl-L-selenocysteine (MSC) and L-selenomethionine (SM) to β-methylselenopyruvate (MSP) and α-ketomethylselenobutyrate (KMSB), respectively. Previous studies have identified these seleno α-keto acids as potent histone deacetylase (HDAC) inhibitors. Methylselenol (CH3SeH), also purported to have chemopreventive properties, is the γ-elimination product of SM and the β-elimination product of MSC catalyzed by cystathionine γ-lyase (γ-cystathionase). KAT I, II, III, in part, can catalyze β-elimination reactions with MSC generating CH3SeH. Thus, the anticancer efficacy of MSC and SM will depend, in part, on the endogenous expression of various KAT enzymes and cystathionine γ-lyase present in target tissue coupled with the ability of cells to synthesize in situ either CH3SeH and/or seleno-keto acid metabolites.