Kynurenine Aminotransferase III and Glutamine Transaminase L Are Identical Enzymes that have Cysteine S-Conjugate β-Lyase Activity and Can Transaminate l-Selenomethionine

Abstract

Background: KAT I and GT-Kidney (K) are identical enzymes that ␤-eliminate and transaminate Se-methyl-L-selenocysteine (MSC). Results: KAT III and GT-Liver (L) are identical and metabolize L-selenomethionine (SM). Conclusion: MSC and SM are transaminated to seleno-keto acids, recognized HDAC inhibitors, by KAT/GT enzymes. Significance: Anticancer efficacy of MSC and SM depends in part on tissue expression of KAT/GT enzymes.

Role of Glutamine Transaminases in Nitrogen, Sulfur, Selenium, and 1-Carbon Metabolism

“…No significant inhibition of MSC transamination was noted in the presence of 1 mM glutamine. Even in the presence of 100 mM glutamine the rate of transamination of MSC was~20 % that observed for the control that lacked added glutamine [5]. This finding is significant because it is unlikely that all potential amino acid competitive inhibitors of GTK in the cell added together can reach a combined concentration of 100 mM.…”

“…K cat /K m values for the next six "best" amino acid substrates, namely histidine, methionine, phenylalanine, asparagine, cysteine, and kynurenine, were reported to be 171, 162, 147, 126, 114, and 92 min −1 mM −1 , respectively. We have shown that KAT III is identical to GTL [5]. Inasmuch as (a) GTK and GTL were described prior to the identification of KAT I and KAT III as distinct kynurenine aminotransferases, (b) glutamine is a better substrate than is kynurenine, (c) mammalian tissues contain far more glutamine than kynurenine, and (d) the present chapter focuses on glutamine, we have assumed the nomenclature GTK and GTL throughout the present chapter, except where it is necessary to indicate the KAT nomenclature often presented in basic scientific literature.…”

“…Consequently, the gene for GTK is named CCBL1 (cysteine S-conjugate β-lyase isozyme 1) in human and rodent genomes. In addition, we have recently identified a closely related gene, named CCBL2, as coding for KAT III/GTL [5]. In our opinion this is an inappropriate nomenclature as the lyase reaction is not the natural reaction catalyzed by GTK and GTL.…”

“…We have obtained similar findings with recombinant human KAT I/GTK (Table 3.1). On the other hand, SM is a relatively good aminotransferase substrate of recombinant mouse KAT III/GTL, but MSC is not as effective (Table 3.1; [5]). …”

“…1,2-Dichloroethylenethiol is unstable and in part loses HCl to form the highly reactive chlorothioketene (4). The thioketene reacts with tissue nucleophiles (Nu:) to generate thioacylated products (5) (6) by cysteine S-conjugate β-lyases. TFEC is converted to pyruvate (2), ammonium and a sulfur-containing fragment that has the structure 1,1,2,2-tetrafluoroethanethiolate (7).…”