Studies on the Mechanism of S-Cysteine Conjugate Metabolism and Toxicity in Rat Liver, Kidney, and a Cell Culture Model

  • James L. Stevens
  • Patrick Hayden
  • Gail Taylor
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)


Cysteine conjugate β-lyases are enzymes which may be involved in the nephrotoxicity caused by a variety of S-cysteine conjugates which are formed from halogenated hydrocarbons.1 The enzymes catalyze the cleavage of S-cysteine conjugates to ammonia pyruvate and a thiol whose sulfur is derived from cysteine (eq. 1).2,3 The thiol containing cleavage fragments may be the species which are responsible for the nephrotoxicity of these compounds. This hypothesis is based on the observations of Schultze and coworkers who investigated the toxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC)4–6. These workers found that DCVC was cleaved by mammalian and bacterial enzymes to pyruvate and ammonia, as well as an unidentified fragment which covalently bound to cellular macromolecules. However, there is no direct evidence linking the metabolism of S-cysteine conjugates and the toxicity of reactive electrophilic metabolites in vivo. In addition, it is not clear why the kidney is the target organ. We have investigated the properties of mammalian cysteine conjugate β-lyases in liver and kidney and developed a model culture system which responds to the toxic effects of a variety of S-cysteine conjugates. With these systems, we hope to establish a mechanism of toxicity for S-cysteine conjugates which are nephrotoxic.


Covalent Binding Pyridoxal Phosphate Cellular Macromolecule Mercapturic Acid Cleavage Fragment 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • James L. Stevens
    • 1
  • Patrick Hayden
    • 1
  • Gail Taylor
    • 1
  1. 1.Division of Biochemistry and BiophysicsCenter for Drugs and Biologics, FDABethesdaUSA

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