Inactivation of brain and kidney aspartate aminotransferases by S-(1,2,-dichlorovinyl)-L-cysteine and by S-(1,1,2,2,-tetrafluoroethyl)-L-cysteine

Developmental Neuroscience
Y KatoA J Cooper

Abstract

Long-term exposure to trichloroethylene can cause kidney cancer in experimental animals and humans. In addition, dichloroacetylene (a breakdown 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-cysteine) 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 lipid peroxidation. We now show that S-(1,2-dichlorovinyl)-L-cysteine and another nephrotoxic cysteine S-conjugate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, inactive purified cytosolic aspartate aminotransferase and purified alanine aminotransferase. These cysteine S-conjugates also inactive aspartate aminotransferase in cytosolic and mitochondrial fractions of rat brain and kidney. The present results suggest that some halogenated xenobiotics may be toxic in part through their conversion to the corresponding cysteine S-conjugate which inactivates key pyridoxal 5'-phosphate-containing enzyme.

Citations

Feb 4, 1999·Journal of Neurochemistry·P S HodgkinsR Schwarcz
Feb 8, 2006·Amino Acids·A J L Cooper, J T Pinto
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S A BruschiJ W Crabb
Jan 31, 2020·Environmental Science. Processes & Impacts·Briana R De Miranda, J Timothy Greenamyre
Sep 3, 2002·Chemico-biological Interactions·Martijn RooseboomJan N M Commandeur

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