Substrate specificity of human glutamine transaminase K as an aminotransferase and as a cysteine S-conjugate beta-lyase.
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-cysteinyldopamine, 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-cysteinyl-l-DOPA and Se-methyl-l-selenocysteine in human tissues and their biological relevance are discussed.
Cooper
Arthur J L
AJ
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA. arthur_cooper@nymc.edu
Pinto
John T
JT
Krasnikov
Boris F
BF
Niatsetskaya
Zoya V
ZV
Han
Qian
Q
Li
Jianyong
J
Vauzour
David
D
Spencer
Jeremy P E
JP
D000596:Amino Acids / Q000378:metabolism; D013437:Carbon-Sulfur Lyases / Q000378:metabolism*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008190:Lyases / Q000378:metabolism*; D010084:Oxidation-Reduction; D013379:Substrate Specificity; D000637:Transaminases / Q000378:metabolism*
D000596:Amino Acids; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C108902:cysteine-S-conjugate beta-lyase