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. 2002 Nov 15;368(Pt 1):253–261. doi: 10.1042/BJ20020531

Mitochondrial aspartate aminotransferase catalyses cysteine S-conjugate beta-lyase reactions.

Arthur J L Cooper 1, Sam A Bruschi 1, Ana Iriarte 1, Marino Martinez-Carrion 1
PMCID: PMC1222959  PMID: 12137566

Abstract

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 [benzothiazolyl-L-cysteine]. Transamination competes with the beta-lyase reaction, but is not favourable. The ratio of beta 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.

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Selected References

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