Mitochondrial aspartate aminotransferase catalyses cysteine S-conjugate β-lyase reactions

Rat liver mitochondrial aspartate aminotransferase (a homodimer) was shown to catalyse a beta-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 [benzothiazolyi-L-cysteine]. Transamination competes with the beta-lyase reaction, but is not favourable. The ratio of 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 beta-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.