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Cooper AJ, Krasnikov BF, Niatsetskaya ZV, Pinto JT, Callery PS, Villar MT, Artigues A, Bruschi SA: Cysteine S-conjugate beta-lyases: important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents. Amino Acids. 2010 Mar 22.
Cysteine S-conjugate beta-lyases are pyridoxal 5'-phosphate-containing enzymes that catalyze beta-elimination reactions with cysteine S-conjugates that possess a good leaving group in the beta-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 beta-lyases thus far identified are enzymes involved in amino acid metabolism that catalyze beta-lyase reactions as non-physiological side reactions. Most are aminotransferases. In some cases the lyase is inactivated by reaction products. The cysteine S-conjugate beta-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 beta-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 beta-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 beta-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 beta-lyases in the metabolism/bioactivation of drugs and natural products; and (5) the role of cysteine S-conjugate beta-lyases in the metabolism of selenocysteine Se-conjugates. This review emphasizes the fact that the cysteine S-conjugate beta-lyases are biologically more important than hitherto appreciated. |
87(1,1,1,7) |