title: Kynurenine aminotransferase III and glutamine transaminase L are identical enzymes that have cysteine S-conjugate β-lyase activity and can transaminate L-selenomethionine.
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.
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and john_pinto@nymc.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Pinto
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and.
authors.forename: Boris F
authors.initials: BF
authors.lastname: Krasnikov
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and.
authors.forename: Steven
authors.initials: S
authors.lastname: Alcutt
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and.
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Jones
authors.affiliation: Urology, New York Medical College, Valhalla, New York 10595.
authors.forename: Thambi
authors.initials: T
authors.lastname: Dorai
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, and.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Villar
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigues
authors.affiliation: the Department of Biochemistry, Virginia Tech, Blacksburg, Virginia 24061.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Departments of Biochemistry and Molecular Biology and arthur_cooper@nymc.edu.
authors.forename: Arthur J L
authors.initials: AJ
authors.lastname: Cooper
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000818:Animals; D013437:Carbon-Sulfur Lyases / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017279:Selenocysteine / Q000737:chemistry; D012645:Selenomethionine / Q000737:chemistry*; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry; D000637:Transaminases / Q000378:metabolism*
chemical_list: D000475:Alkenes; D056572:Histone Deacetylase Inhibitors; D011994:Recombinant Proteins; D017279:Selenocysteine; D012645:Selenomethionine; D000637:Transaminases; C020656:glutamine-pyruvate aminotransferase; C021481:kynurenine-oxoglutarate transaminase; D013437:Carbon-Sulfur Lyases; C019969:S-alkylcysteine lyase; D003545:Cysteine
keywords: Cancer Chemoprevention; Glutamine; Histone Deacetylase Inhibitor (HDAC Inhibitor) (HDI); Mass Spectrometry (MS); Selenocysteine