Rat liver mitochondrial aspartate aminotransferase (a homodimer) was shown to catalyse a β-lyase reaction with three nephrotoxic halogenated cysteine S-conjugates [S-(1,1,2,2-tetrafluoroethyl)-l-cysteine, S-(1,2-dichlorovinyl)-l-cysteine and S-(2-chloro-1,1,2-trifluoroethyl)-l-cysteine], and less effectively so with a non-toxic cysteine S-conjugate [benzothiazolyl-l-cysteine]. Transamination competes with the β-lyase reaction, but is not favourable. The ratio of β elimination to transamination in the presence of S-(1,1,2,2-tetrafluoroethyl)-l-cysteine and 2-oxoglutarate is >100. Syncatalytic inactivation by the halogenated cysteine S-conjugates is also observed. The enzyme turns over approx. 2700 molecules of halogenated cysteine S-conjugate on average for every monomer inactivated. Kidney mitochondria are known to be especially sensitive to toxic halogenated cysteine S-conjugates. Evidence is presented that 15—20% of the cysteine S-conjugate β-lyase activity towards S-(1,1,2,2-tetrafluoroethyl)-l-cysteine in crude kidney mitochondrial homogenates is due to mitochondrial aspartate aminotransferase. The possible involvement of mitochondrial aspartate aminotransferase in the toxicity of halogenated cysteine S-conjugates is also discussed.
Mitochondrial aspartate aminotransferase catalyses cysteine S-conjugate β-lyase reactions
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Arthur J.L. COOPER, Sam A. BRUSCHI, Ana IRIARTE, Marino MARTINEZ-CARRION; Mitochondrial aspartate aminotransferase catalyses cysteine S-conjugate β-lyase reactions. Biochem J 15 November 2002; 368 (1): 253–261. doi: https://doi.org/10.1042/bj20020531
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