CYTOSOLIC C-S LYASE ACTIVITY IN HUMAN KIDNEY SAMPLES - RELEVANCE FOR THE NEPHROTOXICITY OF HALOGENATED ALKENES IN MAN

Human renal cortex cytosolic samples were screened for C-S lyase (EC 4 .4.1.13) activity using cysteine conjugates of halogenated aliphatic a nd aromatic hydrocarbons as substrates. Cytosolic activity was greates t with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,1,2,2-tetraflu oroethyl)-L-cysteine (TFEC) (72.0 +/- 26.8 and 74.4 +/- 38.3 nmol pyru vate formed/mg protein/120 min. respectively). Less than five fold int er-individual variation was observed. In contrast to the low C-S lyase activity detectable in rat cytosol, no cleavage of the aromatic conju gates S-(2-benzothiazolyl)-L-cysteine (BTC), S-(2,3,5,6-tetrachlorophe nyl)-L-cysteine (TCPC) and S-(4-bromophenyl)-L-cysteine (4-BPC) was de tectable in human cytosol. Structure-activity relationships showed tha t increasing the fluorinated carbon chain length of the halogenated hy drocarbon species decreased conjugate cleavage by C-S lyase.