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.
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November 2002
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Research Article|
November 15 2002
Mitochondrial aspartate aminotransferase catalyses cysteine S-conjugate β-lyase reactions Available to Purchase
Arthur J.L. COOPER;
Arthur J.L. COOPER
1
∗Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, U.S.A.
†Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, U.S.A.
‡Burke Medical Research Institute, White Plains, NY 10605, U.S.A.,
1To whom correspondence should be addressed (e-mail [email protected]).
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Sam A. BRUSCHI;
Sam A. BRUSCHI
§Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195—7610, U.S.A.,
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Ana IRIARTE;
Ana IRIARTE
∥Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110—2499, U.S.A.
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Marino MARTINEZ-CARRION
Marino MARTINEZ-CARRION
∥Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110—2499, U.S.A.
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Publisher: Portland Press Ltd
Received:
April 04 2002
Revision Received:
July 19 2002
Accepted:
July 23 2002
Accepted Manuscript online:
July 23 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 368 (1): 253–261.
Article history
Received:
April 04 2002
Revision Received:
July 19 2002
Accepted:
July 23 2002
Accepted Manuscript online:
July 23 2002
Citation
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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