NYMC Faculty Publications
Kynurenine Aminotransferase III and Glutamine Transaminase L Are Identical Enzymes That Have Cysteine S-Conjugate Β-Lyase Activity and Can Transaminate L-Selenomethionine
Author Type(s)
Faculty
DOI
10.1074/jbc.M114.591461
Journal Title
The Journal of Biological Chemistry
First Page
30950
Last Page
61
Document Type
Article
Publication Date
11-7-2014
Abstract
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, and mitochondrial aspartate aminotransferase, respectively. GTK/KAT I and aspartate aminotransferase/KAT IV possess cysteine S-conjugate β-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome data banks 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 data bank, 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 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, respectively. Previous studies have identified these seleno-α-keto acids as potent histone deacetylase 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, and 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.
Recommended Citation
Pinto, J. T., Krasnikov, B. F., Alcutt, S., Jones, M. E., Dorai, T., Villar, M. T., Artigues, A., Li, J., & Cooper, A. J. (2014). Kynurenine Aminotransferase III and Glutamine Transaminase L Are Identical Enzymes That Have Cysteine S-Conjugate Β-Lyase Activity and Can Transaminate L-Selenomethionine. The Journal of Biological Chemistry, 289 (45), 30950-61. https://doi.org/10.1074/jbc.M114.591461