Substrate specificity of human glutamine transaminase K as an aminotransferase and as a cysteine S-conjugate beta-lyase

Cooper, A. J. L., Pinto, J. T., Krasnikov, B. F., Niatsetskaya, Z. V., Han, Q., Li, J. Y., Vauzour, D. and Spencer, J. P. E. ORCID: https://orcid.org/0000-0003-2931-7274 (2008) Substrate specificity of human glutamine transaminase K as an aminotransferase and as a cysteine S-conjugate beta-lyase. Archives of Biochemistry and Biophysics, 474 (1). pp. 72-81. ISSN 0003-9861 doi: 10.1016/j.abb.2008.02.038

Abstract/Summary

Rat kidney glutamine transaminase K (GTK) exhibits broad specificity both as an aminotransferase and as a cysteine S-conjugate beta-lyase. The beta-lyase reaction products are pyruvate, ammonium and a sulfhydryl-containing fragment. We show here that recombinant human GTK (rhGTK) also exhibits broad specificity both as an aminotransferase and as a cysteine S-conjugate beta-lyase. S-(1,1,2,2-Tetrafluoroethyl)-L-CySteine is an excellent aminotransferase and beta-lyase substrate of rhGTK. Moderate aminotransferase and beta-lyase activities occur with the chemopreventive agent Se-methyl-L-selenocysteine. L-3-(2-Naphthyl)alanine, L-3-(1-naphthyl)alanine, 5-S-L-cysteinyldopamine and 5-S-L-cysteinyl-L-DOPA are measurable aminotransferase substrates, indicating that the active site can accommodate large aromatic amino acids. The alpha-keto acids generated by transamination/L-amino acid oxidase activity of the two catechol cysteine S-conjugates are unstable. A slow rhGTK-catalyzed beta-elimination reaction, as measured by pyruvate formation, was demonstrated with 5-S-L-CysteinyIdopamine, but not with 5-S-L-CySteinyl-L-DOPA. The importance of transamination, oxidation and beta-elimination reactions involving 5-S-L-cysteinyldopamine, 5-S-L-cysteinyt-L-DOPA and Se-methyl-L-selenocysteirte in human tissues and their biological relevance are discussed. (C) 2008 Elsevier Inc. All rights reserved.