Halogenated vinyl cysteine conjugates, which are potent, specific nephrotoxins, have been chemically synthesized from both chlorotrifluoroethylene (CTFE) and trichloroethylene (TCE) but have not been shown to be formed in a biological system. The vinyl cysteine conjugates are stable, but rapidly activated and degraded enzymatically with the release of pyruvate. Increased concentrations of pyruvate after incubation with CTFE may be an indirect index of the formation and bioactivation of a vinyl cysteine conjugate of CTFE. Incubation of CTFE with 10,000 x g rat liver and kidney supernatants resulted in 60 and 100 nmole/mg/hr increases in pyruvate concentration with concomitant depletion of endogenous glutathione. A renal cortex brush border preparation high in C-S lyase activity but deficient in cytosolic transferases did not generate pyruvate during incubation with CTFE. The evidence presented suggests that halogenated vinyl cysteine conjugates are formed in vitro by conjugation of the halogenated ethylene with glutathione which subsequently degrades to form the cysteine conjugate.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)