Publications

• Cysteine S-conjugate beta-lyases: important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents.

  Cooper A.J., Krasnikov B.F., Niatsetskaya Z.V., Pinto J.T., Callery P.S., Villar M.T., Artigues A., Bruschi S.A.

  Cysteine S-conjugate β-lyases are pyridoxal 5'-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess a good leaving group in the β-position. The end products are aminoacrylate and a sulfur-containing fragment. The aminoacrylate tautomerizes and ... >> More

  Cysteine S-conjugate β-lyases are pyridoxal 5'-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess a good leaving group in the β-position. The end products are aminoacrylate and a sulfur-containing fragment. The aminoacrylate tautomerizes and hydrolyzes to pyruvate and ammonia. The mammalian cysteine S-conjugate β-lyases thus far identified are enzymes involved in amino acid metabolism that catalyze β-lyase reactions as non-physiological side reactions. Most are aminotransferases. In some cases the lyase is inactivated by reaction products. The cysteine S-conjugate β-lyases are of much interest to toxicologists because they play an important key role in the bioactivation (toxication) of halogenated alkenes, some of which are produced on an industrial scale and are environmental contaminants. The cysteine S-conjugate β-lyases have been reviewed in this journal previously (Cooper and Pinto in Amino Acids 30:1-15, 2006). Here, we focus on more recent findings regarding: (1) the identification of enzymes associated with high-M(r) cysteine S-conjugate β-lyases in the cytosolic and mitochondrial fractions of rat liver and kidney; (2) the mechanism of syncatalytic inactivation of rat liver mitochondrial aspartate aminotransferase by the nephrotoxic β-lyase substrate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (the cysteine S-conjugate of tetrafluoroethylene); (3) toxicant channeling of reactive fragments from the active site of mitochondrial aspartate aminotransferase to susceptible proteins in the mitochondria; (4) the involvement of cysteine S-conjugate β-lyases in the metabolism/bioactivation of drugs and natural products; and (5) the role of cysteine S-conjugate β-lyases in the metabolism of selenocysteine Se-conjugates. This review emphasizes the fact that the cysteine S-conjugate β-lyases are biologically more important than hitherto appreciated. << Less

  Amino Acids 41:7-27(2011) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Cysteine conjugate beta-lyase in rat liver. A novel enzyme catalyzing formation of thiol-containing metabolites of drugs.

  Tateishi M., Suzuki S., Shimizu H.

  A novel enzyme catalyzing cleavage of the thioether linkage in cysteine conjugates of aromatic compounds, such as 2,4-dinitrobenzene and p-bromobenzene, has been purified about 500-fold from rat liver cytosol. Incubation of S-(2,4-dinitrophenyl)cysteine with the enzyme preparation yielded 2,4-dini ... >> More

  A novel enzyme catalyzing cleavage of the thioether linkage in cysteine conjugates of aromatic compounds, such as 2,4-dinitrobenzene and p-bromobenzene, has been purified about 500-fold from rat liver cytosol. Incubation of S-(2,4-dinitrophenyl)cysteine with the enzyme preparation yielded 2,4-dinitrobenzenethiol, pyruvic acid, and NH3 at equimolar ratios, indicating that the thioether cleavage probably proceeds via an alpha,beta elimination reaction. The thiol product was methylated and the methylated derivative 1-methylthio-2,4-dinitrobenzene, was identified by mass spectrometry and proton NMR spectroscopy. The Km value of S-(2,4-dinitrophenyl)cysteine was 0.5 mM at pH 7.4 in phosphate buffer. The enzyme activity was inhibited by hydroxylamine. No cofactor requirement was observed. A combination of the partially purified enzyme and hepatic microsomes that contain thiol methyltransferase (EC 2.1.1.9) converted cysteine conjugates of 2,4-dinitrobenzene and p-bromobenzene to the corresponding methylthio-containing metabolites; S-adenosylmethionine was required. An important role of this novel beta-lyase enzyme in the formation of methylthio-containing metabolites of various drugs is indicated. << Less

  J Biol Chem 253:8854-8859(1978) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.