INACTIVATION OF BRAIN AND KIDNEY ASPARTATE AMINOTRANSFERASES BY S-(1,2-DICHLOROVINYL)-L-CYSTEINE AND BY S-(1,1,2,2-TETRAFLUOROETHYL)-L-CYSTEINE

Long-term exposure to trichloroethylene can cause kidney cancer in exp erimental animals and humans, In addition, dichloroacetylene (a breakd own product of trichloroethylene) is nephrotoxic and neurotoxic. Both trichloroethylene and dichloroacetylene are metabolized in part to the corresponding cysteine S-conjugate (i.e. S-(1,2-dichlorovinyl)-L-cyst eine) which is toxic, Cysteine S-conjugate beta-lyases convert S-(1,2- dichlorovinyl)-L-cysteine to pyruvate, ammonia and a reactive fragment that adds to macromolecules, depletes cellular thiols and causes lipi d peroxidation. We now show that S(1,2-dichlorovinyl)-L-cysteine and a nother nephrotoxic cysteine S-conjugate, S-(1,1,2,2-tetrafluoroethyl)- L-cysteine, inactivate purified cytosolic aspartate aminotransferase a nd purified alanine aminotransferase, These cysteine S-conjugates also inactivate aspartate aminotransferase in cytosolic and mitochondrial fractions of rat brain and kidney, The present results suggest that so me halogenated xenobiotics may be toxic in part through their conversi on to the corresponding cysteine S-conjugate which inactivates key pyr idoxal 5'-phosphate-containing enzymes.