Substrate specificity of human glutamine transaminase K as an aminotransferase and as a cysteine S-conjugate β-lyase
Substrate specificity of human glutamine transaminase K as an aminotransferase and as a cysteine S-conjugate β-lyase
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DOI：
10.1016/j.abb.2008.02.038
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发表时间：
2008-06-01
影响因子：
3.9
通讯作者：
Spencer, Jeremy P. E.
中科院分区：
文献类型：
--
作者：
Cooper, Arthur J. L.;Pinto, John T.;Spencer, Jeremy P. E.
大鼠肾脏谷氨酰胺转氨酶K(GTK)既是一种转氨酶，又是一种半胱氨酸S结合的β-裂解酶，具有广泛的特异性。β-裂解酶反应产物为丙酮酸、铵和含硫的碎片。在此，我们发现重组人GTK(Rh GTK)既是一种转氨酶，也是一种半胱氨酸S结合的β-裂解酶，具有广泛的特异性。S-(1，1，2，2-四氟乙基)-L-半胱氨酸是重组人谷氨酸氨基转移酶和β-裂解酶的优良底物。化学预防药物硒-甲基-L-硒半胱氨酸具有中等的转氨酶和β-裂解酶活性。L-3-(2-萘基)丙氨酸、L-3-(1-萘基)丙氨酸、5-S-L-半胱氨酸多巴胺和5-S-L-半胱氨基-L-多巴是可检测到的氨基转移酶底物，表明活性部位可以容纳大量芳香氨基酸。两种邻苯二酚半胱氨酸S-偶联物转氨生成的α-酮酸/L-氨基酸氧化酶活性不稳定。5-S-L-半胱氨酸-多巴胺存在缓慢的β-消除反应，而5-S-L-半胱氨基-L-多巴则不存在。讨论了5-S-L-半胱氨酸多巴胺、5-S-L-半胱氨酸-L-多巴和硒-甲基-L-硒半胱氨酸在人体组织中转氨基、氧化和β-消除反应的重要性及其生物学意义。(C)2008 Elsevier Inc.保留所有权利。
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.