Metabolism of S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine to hydrogen sulfide and the role of hydrogen sulfide in S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine-induced mitochondrial toxicity.
The nephrotoxic cysteine S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) is metabolized by kidney homogenates and subcellular fractions to pyruvate and a reactive thiol, which is cytotoxic and partially decomposes to yield hydrogen sulfide and thiosulfate. Although hydrogen sulfide is a potent mitochondrial poison, the mitochondrial toxicity of CTFC is not attributable to hydrogen sulfide formation, as shown by different sites of inhibition of mitochondrial respiration by CTFC and hydrogen sulfide. The efficient mitochondrial oxidation of hydrogen sulfide apparently serves to protect mitochondria against the toxic effects of hydrogen sulfide generated from CTFC.
D000818:Animals; D001711:Biotransformation; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D003600:Cytosol / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012402:Rotenone / Q000494:pharmacology
D012402:Rotenone; C047601:S-(2-chloro-1,1,2-trifluoroethyl)cysteine; D003545:Cysteine; D006862:Hydrogen Sulfide