Amino Acids

, Volume 41, Issue 1, pp 7–27 | Cite as

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

  • Arthur J. L. CooperEmail author
  • Boris F. Krasnikov
  • Zoya V. Niatsetskaya
  • John T. Pinto
  • Patrick S. Callery
  • Maria T. Villar
  • Antonio Artigues
  • Sam A. Bruschi
Review Article


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.


Cysteine S-conjugates Cysteine S-conjugate β-lyases S-(1,2-Dichlorovinyl)-l-cysteine Glutamine transaminase K Mitochondrial aspartate aminotransferase S-(1,1,2,2-tetrafluoroethyl)-l-cysteine 



Alanine aminotransferase


Alanine-glyoxylate aminotransferase isoenzyme II


Cytosolic branched-chain aminotransferase


Mitochondrial branched-chain aminotransferase


Branched-chain α-keto acid dehydrogenase complex




Cytosolic aspartate aminotransferase








Electrospray ionization-mass spectrometry




Glutathione S-transferase


Glutamine transaminase K


Heat shock protein 60 kDa


Heat shock protein 70 kDa (inducible isoform)


Cytosolic HSP70


Kynurenine aminotransferase isoenzyme I


α-Ketoglutarate dehydrogenase complex


Mitochondrial aspartate aminotransferase


Mitochondrial aconitase


Heat shock protein 70 kDa (mitochondrial isoform)


Mitochondrial GTK


Precursor to mAAT


Pyruvate dehydrogenase complex


Pyridoxal 5′-phosphate


Pyridoxamine 5′-phosphate





TCA cycle

Tricarboxylic acid cycle


Trifluoroacetic acid









Part of the work cited from the authors’ laboratories was supported by NIH grants RO1 ES8421 (AJLC), CA111842 (JTP), GM51916 (SAB) National Institute of Justice Grant IJ-CX-K014 (PSC),University of Kansas Medical Center ROV10525 (AA).


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Arthur J. L. Cooper
    • 1
    Email author
  • Boris F. Krasnikov
    • 1
  • Zoya V. Niatsetskaya
    • 2
  • John T. Pinto
    • 1
  • Patrick S. Callery
    • 3
  • Maria T. Villar
    • 4
  • Antonio Artigues
    • 4
  • Sam A. Bruschi
    • 5
  1. 1.Department of Biochemistry and Molecular BiologyNew York Medical CollegeValhallaUSA
  2. 2.Columbia UniversityNew YorkUSA
  3. 3.Department of Basic Pharmaceutical Sciences, School of PharmacyWest Virginia UniversityMorgantownUSA
  4. 4.Department of Biochemistry and Molecular BiologyUniversity of Kansas Medical CenterKansas CityUSA
  5. 5.Laural ConsultingAdelaideAustralia

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