Amino Acids

, Volume 30, Issue 1, pp 1–15 | Cite as

Cysteine S-conjugate β-lyases

  • A. J. L. Cooper
  • J. T. Pinto
Review Article


Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess an electron-withdrawing group attached at the sulfur. The end products of the β-lyase reaction are pyruvate, ammonium and a sulfur-containing fragment. If the sulfur-containing fragment is reactive, the parent cysteine S-conjugate may be toxic, particularly to kidney mitochondria. Halogenated alkenes are examples of electrophiles that are bioactivated (toxified) by conversion to cysteine S-conjugates. These conjugates are converted by cysteine S-conjugate β-lyases to thioacylating fragments. Several cysteine S-conjugates found in allium foods (garlic and onion) are β-lyase substrates. This finding may account in part for the chemopreventive activity of allium products. This review (1) identifies enzymes that catalyze cysteine S-conjugate β-lyase reactions, (2) suggests that toxicant channeling may contribute to halogenated cysteine S-conjugate-induced toxicity to mitochondria, and (3) proposes mechanisms that may contribute to the antiproliferative effects of sulfur-containing fragments eliminated from allium-derived cysteine S-conjugates.

Keywords: Cysteine S-conjugates – Cysteine S-conjugate β-lyases – S-(1,2-dichlorovinyl)-L-cysteine – Glutamine transaminase K – Mitochon drial aspartate aminotransferase – S-(1,1,2,2-tetrafluoroethyl)-L-cysteine – Allium-derived compounds 

Abbreviations used:


alanine aminotransferase


alanine-glyoxylate aminotransferase isoenzyme II


cytosolic branched-chain aminotransferase


mitochondrial branched-chain aminotransferase


branched-chain α-keto acid dehydrogenase complex




cytosolic aspartate aminotransferase




glutathione S-transferase


glutamine transaminase K


kynurenine aminotransferase isoenzyme I


α-ketoglutarate dehydrogenase complex


mitochondrial aspartate aminotransferase


pyruvate dehydrogenase complex


pyridoxal 5′-phosphate


pyridoxamine 5′-phosphate





TCA cycle

tricarboxylic acid cycle




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  1. Abraham, DG, Thomas, RJ, Cooper, AJL 1995aGlutamine transaminase K is not a major cysteine S-conjugate β-lyase of rat kidney mitochondria: evidence that a high-molecular-weight enzyme fulfills this role.Mol Pharmacol48855860Google Scholar
  2. Abraham, DG, Patel, P, Cooper, AJL 1995bIsolation from rat kidney of a high molecular weight cysteine S-conjugate β-lyase with activity toward leukotriene E4.J Biol Chem270180188Google Scholar
  3. Adcock, HJ, Gaskin, PJ, Shaw, PN, Teesdale-Spittle, PH, Buckberry, LD 1996Novel sources of mammalian C-S lyase activity.J Pharm Pharmacol48150153PubMedGoogle Scholar
  4. Anders, MW 2004Glutathione-dependent bioactivation of haloalkanes and haloalkenes.Drug Metab Rev36583594PubMedCrossRefGoogle Scholar
  5. Anders, MW 2005Formation and toxicity of anesthetic degradation products.Annu Rev Pharmacol Toxicol45147176PubMedCrossRefGoogle Scholar
  6. Baumann, E 1883Über die Bildung der Mercaptursäuren in Organismus und ihre Erkennung im Harn.Hoppe-Seylers Physiol Chem84190197Google Scholar
  7. Beal, MF 2000Energetics in the pathogenesis of neurodegenerative diseases.Trends Neurosci23298304PubMedCrossRefGoogle Scholar
  8. Bhattacharya, RK, Schultze, MO 1967Enzymes from bovine and turkey kidneys which cleave S-(1,2-dichlorovinyl)-L-cysteine.Comp Biochem Physiol22723735PubMedGoogle Scholar
  9. Brauch, H, Weirich, G, Klein, B, Rabstein, S, Bolt, HM, Bruning, T 2004VHL mutations in renal cell cancer: does occupational exposure to trichloroethylene make a difference?Toxicol Lett151301310PubMedCrossRefGoogle Scholar
  10. Bruschi, SA, West, KA, Crabb, JW, Gupta, RS, Stevens, JL 1993Mitochondrial HSP60 (P1 protein) and HSP70-like protein (mortalin) are major targets for modification during S-(1,1,2,2-tetrafluoroethyl)-L-cysteine-induced toxicity.J Biol Chem2682315723161PubMedGoogle Scholar
  11. Bruschi, SA, Crabb, JW, Stevens, JL 1994The E3 subunit of 2-oxoglutarate, branched-chain α-keto acid, and malate dehydrogenase are adducted during nephrotoxic cysteine-conjugate injury.Toxicologist14428(Abstract)Google Scholar
  12. Bruschi, SA, Lindsay, JG, Crabb, JW 1998Mitochondrial stress protein recognition of inactivated dehydrogenases during mammalian cell death.Proc Natl Acad Sci USA951341313418PubMedCrossRefGoogle Scholar
  13. Buckberry, LD, Blagbrough, IS, Bycroft, BW, Shaw, PN 1992Kynurenine aminotransferase activity in human liver. Identity with hepatic C-S lyase activity and a physiological role for this enzyme.Toxicol Lett60241246PubMedCrossRefGoogle Scholar
  14. Buckberry, LD, Patel, R, Hollingworth, L, Teesdale-Spittle, PH 1998Cysteine conjugate β-lyase activity of amino acid decarboxylases.Biochem Soc Trans26269SGoogle Scholar
  15. Bull, RJ, Orner, GA, Cheng, RS, Stillwell, L, Stauber, AJ, Sasser, LB, Lingohr, MK, Thrall, BD 2002Contribution of dichloroacetate and trichloroacetate to liver tumor induction in mice by trichloroethylene.Toxicol Appl Pharmacol1825565PubMedCrossRefGoogle Scholar
  16. Chen, Q, Jones, TW, Brown, PC, Stevens, JL 1990The mechanism of cysteine conjugate cytotoxicity in renal epithelial cells. Covalent binding leads to thiol depletion and lipid peroxidation.J Biol Chem12652160321611Google Scholar
  17. Colucci, DF, Buyske, DA 1965The biotransformation of a sulfonamide to a mercaptan and to mercapturic acid and glucuronide conjugates.Biochem Pharmacol14457466PubMedCrossRefGoogle Scholar
  18. Commandeur, JNM, Andreadou, I, Rooseboom, M, Out, M, De Leur, LJ, Groot, E, Vermeulen, NPE 2000Bioactivation of selenocysteine Se-conjugates by a highly purified rat renal cysteine conjugate β-lyase/glutamine transaminase K.J Pharmacol Exp Ther294753761PubMedGoogle Scholar
  19. Cooper AJL (1988) Glutamine aminotransferases and ω-amidases. In: Kvamme E (ed) Glutamine and glutamate in mammals, vol 1. CRC Press, Boca Raton, Florida, pp 33–52Google Scholar
  20. Cooper, AJL 1994Enzymology of cysteine S-conjugate β-lyases.Adv Pharmacol2771113PubMedGoogle Scholar
  21. Cooper, AJL 1998Mechanisms of cysteine S-conjugate β-lyases.Adv Enzymol72199238PubMedGoogle Scholar
  22. Cooper, AJL 2004The role of glutamine transaminase K (GTK) in sulfur and α-keto acid metabolism in the brain, and the possible bioactivation of neurotoxicants.Neurochem Int44121CrossRefGoogle Scholar
  23. Cooper, AJL, Meister, A 1974Isolation and properties of a new glutamine transaminase from rat kidney.J Biol Chem24925542561PubMedGoogle Scholar
  24. Cooper, AJL, Meister, A 1981Comparative studies of glutamine transaminases from rat tissues.Comp Biochem Physiol69B137145Google Scholar
  25. Cooper, AJL, Pinto, JT 2005Aminotransferase, L-amino acid oxidase and β-lyase reactions involving cysteine S-conjugates found in allium extracts. Relevance to biological activity?Biochem Pharmacol69209220PubMedCrossRefGoogle Scholar
  26. Cooper AJL, Tate SS (1997) Enzymes involved in processing of glutathione conjugates. In: Sipes IG, McQueen CA, Gandolfi AJ (series eds), Guengerich FP (volume ed) Comprehensive toxicology: volume 3, biotransformations. Elsevier, Oxford, pp 329–363Google Scholar
  27. Cooper, AJL, Stephani, RA, Meister, A 1976Enzymatic reactions of methionine sulfoximine. Conversion to the corresponding α-imino and α-keto acids, and to α-ketobutyrate and methane sulfinamide.J Biol Chem25166746682PubMedGoogle Scholar
  28. Cooper, AJL, Wang, J, Gartner, CA, Bruschi, SA 2001Co-purification of mitochondrial HSP70 and mature protein disulfide isomerase with a functional rat kidney high-Mr cysteine S-conjugate β-lyase.Biochem Pharmacol6213451353PubMedCrossRefGoogle Scholar
  29. Cooper, AJL, Bruschi, SA, Anders, MW 2002aToxic, halogenated cysteine S-conjugates and targeting of mitochondrial enzymes of energy metabolism.Biochem Pharmacol64553564CrossRefGoogle Scholar
  30. Cooper, AJL, Bruschi, SA, Iriarte, A, Martinez-Carrion, M 2002bMitochondrial aspartate aminotransferase catalyses cysteine S-conjugate β-lyase reactions.Biochem J368253261CrossRefGoogle Scholar
  31. Cooper, AJL, Bruschi, SA, Conway, M, Hutson, SM 2003aHuman mitochondrial and cytosolic branched-chain aminotransferases are cysteine S-conjugate β-lyases, but turnover leads to inactivation.Biochem Pharmacol65181192CrossRefGoogle Scholar
  32. Cooper, AJL, Krasnikov, B, Okuno, E, Jeitner, TM 2003bL-Alanine-glyoxylate aminotransferase II of rat kidney and liver mitochondria possesses cysteine S-conjugate β-lyase activity. A contributing factor to the nephrotoxicity/hepatotoxicity of halogenated alkenes?Biochem J376169178CrossRefGoogle Scholar
  33. Cummings, BS, Parker, JC, Lash, LL 2000Role of cytochrome P450 and glutathione S-transferase α in the metabolism and cytotoxicity of trichloroethylene in the rat.Biochem Pharmacol59531543PubMedCrossRefGoogle Scholar
  34. Dekant, W, Schrenk, D, Vamvakas, S, Henschler, D 1988aMetabolism of hexachloro-1,3-butadiene in mice: in vivo and in vitro evidence for activation by glutathione conjugation.Xenobiotica18803806Google Scholar
  35. Dekant, W, Vamvakas, S, Henschler, D, Anders, MW 1988bEnzymatic conjugation of hexachloro-1,3-butadiene with glutathione. Formation of 1-(glutathion-S-yl)-1,2,3,4,4-pentachlorobuta-1,3-diene and 1,4-bis(glutathion-S-yl)-1,2,3,4-tetrachlorobuta-1,3-diene.Drug Metab Dispos16701706Google Scholar
  36. Dekant, W, Vamvakas, S, Koob, M, Kochling, A, Kanhai, W, Muller, D, Henschler, D 1990A mechanism of haloalkene-induced renal carcinogenesis.Environ Health Perspect88107110PubMedGoogle Scholar
  37. Dekant, W, Vamvakas, S, Anders, MW 1994Formation and fate of nephrotoxic and cytotoxic glutathione S-conjugates: Cysteine conjugate β-lyase pathway.Adv Pharmacol27114162Google Scholar
  38. Elfarra, AA, Hwang, IY 1990In vivo metabolites of S-(2-benzothiazolyl)-L-cysteine as markers of in vivo cysteine conjugate β-lyase and thiol glucuronosyl transferase activities.Drug Metab Dispos18917922PubMedGoogle Scholar
  39. Elfarra, AA, Hwang, IY 1991Targeting of 6-mercaptopurine to the kidneys. Metabolism and kidney-selectivity of S-(6-purinyl)-L-cysteine analogs in rats.Drug Metab Dsipos21841845Google Scholar
  40. Elfarra, AA, Hwang,  1996Effects of pH, temperature, and chemical structure on the stability of S-(purin-6-yl)-L-cysteine: evidence for a novel molecular rearrangement mechanism to yield N-(purin-6-yl)-L-cysteine.Chem Res Toxicol9654658PubMedCrossRefGoogle Scholar
  41. Elfarra, AA, Lash, LH, Anders, MW 1986Metabolic activation and detoxification of nephrotoxic cysteine and homocysteine S-conjugates.Proc Natl Acad Sci USA8326672671PubMedGoogle Scholar
  42. Elfarra, AA, Duescher, RJ, Hwang, IY, Sicuri, AR, Nelson, JA 1995Targeting 6-thioguanine to the kidney with S-(guanin-6-yl)-L-cysteine.J Pharmacol Exp Ther27412981304PubMedGoogle Scholar
  43. Finkelstein, MB, Dekant, W, Anders, MW 1996Cysteine conjugate β-lyase-catalyzed bioactivation of bromine-containing cysteine S-conjugates: stoichiometry and formation of 2,2-difluoro-3-halothiiranes.Chem Res Toxicol9227231PubMedCrossRefGoogle Scholar
  44. Fleischauer, AT, Poole, CA, Arab, L 2000Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers.Am J Clin Nutr7210471052PubMedGoogle Scholar
  45. Ganther, HE 1999Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase.Carcinogenesis2016571666PubMedCrossRefGoogle Scholar
  46. Gaskin, PJ, Adcock, HJ, Buckberry, LD, Teesdale-Spittle, PH, Shaw, PN 1995The C-S-lysis of L-cysteine conjugates by aspartate and alanine aminotransferase enzymes.Hum Exp Toxicol14422427PubMedGoogle Scholar
  47. Hargus, SJ, Fitzsimmons, ME, Aniya, Y, Anders, MW 1991Stereochemistry of the microsomal glutathione S-transferase catalyzed addition of glutathione to chlorotrifluoroethene.Biochemistry30717721PubMedCrossRefGoogle Scholar
  48. Hayden, PJ, Stevens, JL 1990Cysteine conjugate toxicity, metabolism and binding to macromolecules in isolated rat kidney mitochondria.Mol Pharmacol37468476PubMedGoogle Scholar
  49. Hayes, JD, Flanagan, JU, Jowsey, IR 2005Glutathione transferases.Annu Rev Pharmacol Toxicol455188PubMedCrossRefGoogle Scholar
  50. Ho, HK, Hu, ZH, Tzung, SP, Hockenbery, DM, Fausto, N, Nelson, SD, Bruschi, SA 2005aBCL-xL overexpression effectively protects against tetrafluoroethylcysteine-induced intramitochondrial damage and death.Biochem Pharmacol69147157CrossRefGoogle Scholar
  51. Ho, HK, White, CC, Fernandez, C, Fausto, N, Kavanagh, TJ, Nelson, SD, Bruschi, SA 2005bNrf2 activation involves an oxidative stress independent pathway in tetrafluoroethylcysteine-induced cytotoxicity.Toxicol Sci86354364CrossRefGoogle Scholar
  52. Hollander, MM, Reiter, AJ, Horner, WH, Cooper, AJL 1989Conversion of canavanine to α-keto-γ-guanidinooxybutyrate and to vinylglyoxylate and 2-hydroxyguanidine.Arch Biochem Biophys270698713PubMedCrossRefGoogle Scholar
  53. Hwang, IY, Elfarra, AA 1991Kidney-selective prodrugs of 6-mecaptopurine: biochemical basis of the kidney selectivity of S-(6-purinyl)-L-cysteine and metabolism of new analogs in rats.J Pharmacol Exp Ther258171177PubMedGoogle Scholar
  54. Iciek, I, Włodek, L 2001Biosynthesis and biological properties of compounds containing highly reactive, reduced sulfane sulfur.Polish J Pharmacol53215225Google Scholar
  55. Jaffe, DR, Hassall, CD, Brendel, K, Gandolfi, AJ 1983In vivo and in vitro nephrotoxicity of the cysteine conjugate of hexachlorobutadiene.Toxicol Environ Health11857856Google Scholar
  56. James, EA, Gygi, SP, Adams, ML, Pierce, RH, Fausto, N, Aebersold, RH, Nelson, SD, Bruschi, SA 2002Mitochondrial aconitase modification, functional inhibition, and evidence for a supramolecular complex of the TCA cycle by the renal toxicant S-(1,1,2,2-tetrafluoroethyl)-L-cysteine.Biochemistry2867896797Google Scholar
  57. Jolivette, LJ, Anders, MW 2002Structure-activity relationship for biotransformations of haloalkenes by rat liver microsomal glutathione transferase 1.Chem Res Toxicol1510361041PubMedCrossRefGoogle Scholar
  58. Jones, TW, Qin, C, Schaeffer, VH, Stevens, JL 1988Immunohistochemical localization of glutamine transaminase K, a rat kidney cysteine conjugate β-lyase, and the relationship to the segment specificity of cysteine conjugate nephrotoxicity.Mol Pharmacol34621627PubMedGoogle Scholar
  59. Kanhai, W, Koob, M, Dekant, W, Henschler, D 1991Metabolism of 14C-dichloroacetylene in rats.Xenobiotica21905910PubMedGoogle Scholar
  60. Kato, Y, Asano, Y, Cooper, AJL 1996Inactivation of brain and kidney aspartate aminotransferases by S-(1,2-dichlorovinyl)-L-cysteine and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine.Dev Neurosci18505514PubMedGoogle Scholar
  61. Koob, M, Dekant, W 1991Bioactivation of xenobiotics by formation of toxic glutathione conjugates.Chem Biol Interact77107136PubMedGoogle Scholar
  62. Lash, LH, Nelson, RM, Van Dyke, R, Anders, MW 1990aPurification and characterization of human kidney cytosolic conjugate β-lyase activity.Drug Metab Dispos185054Google Scholar
  63. Lash, LH, Elfarra, AA, Rakiewicz-Nemeth, D, Anders, MW 1990bBioactivation of cytotoxic homocysteine S-conjugates.Arch Biochem Biophys276322330CrossRefGoogle Scholar
  64. Lash, LH, Sausen, PJ, Duescher, RJ, Cooley, AJ, Elfarra, AA 1994Roles of cysteine conjugate β-lyase and S-oxidase in nephrotoxicity: studies with S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)-L-cysteine sulfoxide.J Pharmacol Exp Ther269374383PubMedGoogle Scholar
  65. Lash, LH, Xu, Y, Elfarra, AA, Duescher, RJ, Parker, JC 1995Glutathione-dependent metabolism of trichloroethylene in isolated liver and kidney cells of rats and its role in mitochondrial and cellular toxicity.Drug Metab Dispos23846853PubMedGoogle Scholar
  66. Lash, LH, Shivnani, A, Mai, J, Chinnaiyan, P, Krause, RJ, Elfarra, AA 1997Renal cellular transport, metabolism, and cytotoxicity of S-(6-purinyl)glutathione, a prodrug of 6-mercaptopurine, and analogues.Biochem Pharmacol5413411349PubMedCrossRefGoogle Scholar
  67. Lash, LH, Putt, DA, Hueni, SE, Krause, RJ, Elfarra, AA 2003Roles of necrosis, apoptosis, and mitochondrial dysfunction in S-(1,2-dichlorovinyl)-L-cysteine sulfoxide-induced cytotoxicity in primary cultures of human renal proximal tubular cells.J Pharmacol Exp Ther30511631172PubMedGoogle Scholar
  68. Lock, EA, Ishmael, J 1998The nephrotoxicity and hepatotoxicity of 1,1,2,2-tetrafluoroethyl-L-cysteine in the rat.Arch Toxicol72347354PubMedCrossRefGoogle Scholar
  69. Lock, EA, Sani, Y, Moore, RB, Finkelstein, MB, Anders, MW, Seawright, AA 1996Bone marrow and renal injury associated with haloalkene cysteine conjugates in calves.Arch Toxicol70607619PubMedCrossRefGoogle Scholar
  70. MacFarlane, M, Foster, JR, Gibson, GG, King, LJ, Lock, EA 1989Cysteine conjugate β-lyase of rat kidney cytosol: Characterization, immunocytochemical localization, and correlation with hexachlorobutadiene nephrotoxicity.Toxicol Appl Pharmacol98185197PubMedCrossRefGoogle Scholar
  71. Malherbe, P, Alberati-Giani, D, Köhler, C, Cesura, AM 1995Identification of a mitochondrial form of kynurenine aminotransferase/glutamine transaminase K from rat brain.FEBS Lett367141144PubMedCrossRefGoogle Scholar
  72. Marjot, R, McLeod, AA 1989Chronic non-neurological toxicity from volatile substance abuse.Hum Toxicol8301306PubMedGoogle Scholar
  73. McKinney, LL, Picken, JC,Jr, Weakley, F, Eldridge, AC, Campbell, RE, Cowan, JC, Biester, HE 1959Possible toxic factor of trichloroethylene-extracted soybean oil meal.J Am Chem Soc1959909915Google Scholar
  74. McCartney, RG, Rice, JE, Sanderson, SJ, Bunik, V, Lindsay, H, Lindsay, JG 1998Subunit interactions in the mammalian α-ketoglutarate dehydrogenase components.J Biol Chem2372415924164Google Scholar
  75. McLellan, LI, Wolf, CR, Hayes, JD 1989Human microsomal glutathione S-transferase. Its involvement in the conjugation of hexachloro-1,3-butadiene with glutathione.Biochem J2588793PubMedGoogle Scholar
  76. Miles EW (1986) Pyridoxal phosphate enzymes catalyzing β-elimination and β-replacement reactions. In: Dolphin D, Poulson R, Avramovic O (eds) Vitamin B6 pyridoxal phosphate. Wiley, New York, pp 253–310Google Scholar
  77. Mosca, M, Croci, C, Mostardini, M, Breton, J, Malyszko, J, Avanzi, N, Toma, S, Benatti, L, Gatti, S 2003Tissue expression and translational control of rat kynurenine aminotransferase/glutamine transaminase K mRNAs.Biochim Biophys Acta1628110PubMedGoogle Scholar
  78. Nash, JA, King, LJ, Lock, EA, Green, T 1984The metabolism and disposition of hexachloro-1:3-butadiene in the rat and its relevance to nephrotoxicity.Toxicol Appl Pharmacol73124137PubMedCrossRefGoogle Scholar
  79. Nguyen, T, Sherratt, PJ, Nioi, P, Yang, CS, Pickett, CB 2005Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap 1.J Biol Chem2803248532492PubMedGoogle Scholar
  80. Odum, J, Green, T 1982The metabolism and toxicity of tetrafluoroethylene in the rat.Toxicol Appl Pharmacol76306318Google Scholar
  81. Park, LCH, Gibson, GE, Bunik, V, Cooper, AJL 1999Inhibition of select mitochondrial enzymes in PC12 cells exposed to S-(1,1,2,2-tetrafluoroethyl)-L-cysteine.Biochem Pharmacol5815571565PubMedCrossRefGoogle Scholar
  82. Pfaller, W, Gstraunthaler, G 1998Nephrotoxicity testing in vitro – what we know and what we need to know.Environ Health Perspect106559569PubMedGoogle Scholar
  83. Pinto JT, Lapsia S, Shah A, Santiago H, Kim G (2001) Antiproliferative effects of garlic-derived and other allium related compounds. In: Go VLW (ed) Nutrition and cancer prevention: new insights into the role of phytochemicals. Kluwer Academic, New York, pp 83–106 (Advances in experimental medicine and biology, vol 492)Google Scholar
  84. Pinto JT, Krasnikov BF, Cooper AJL (2005) Antiproliferative effects of garlic and its potential chemopreventive activity. J Nutr (In Press)Google Scholar
  85. Pushkin, A, Carpenito, G, Abuladze, N, Newman, D, Tsuprun, V, Ryazantsev, S, Motemoturu, S, Sassani, P, Solovieva, N, Dukkipati, R, Kurtz, I 2004Structural characterization, tissue distribution, and functional expression of murine aminoacylase III.Am J Physiol Cell Physiol286C848C856PubMedCrossRefGoogle Scholar
  86. Ovadi, J, Srere, PA 2000Macromolecular compartmentation and channeling.Int Rev Cytol192255280PubMedGoogle Scholar
  87. Rhodes, D, Gage, DA, Cooper, AJL, Hanson, AD 1997S-Methylmethionine conversion to dimethylsulfoniopropionate: evidence for an unusual transamination reaction.Plant Physiol11515411548PubMedGoogle Scholar
  88. Rooseboom, M, Vermeulen, NPE, Andreadou, I, Commandeur, JNM 2000Evaluation of the kinetics of β-elimination reactions of selenocysteine Se-conjugates in human renal cytosol: possible implications for the use as kidney selective prodrugs.J Pharmacol Exp Ther294762769PubMedGoogle Scholar
  89. Rooseboom, M, Commandeur, JNM, Floor, GC, Rettie, AE, Vermeulen, NPE 2001aSelenoxidation by flavin-containing monooxygenases as a novel pathway for β-elimination of selenocysteine Se-conjugates.Chem Res Toxicol14127134Google Scholar
  90. Rooseboom, M, Vermeulen, NPE, van Hemert, N, Commandeur, JNM 2001bBioactivation of chemopreventive selenocysteine Se-conjugates and related amino acids by amino acid oxidases – novel route of metabolism of selenoamino acids.Chem Res Toxicol149961005Google Scholar
  91. Rooseboom, M, Vermeulen, NPE, Durgut, F, Commandeur, JNM 2002Comparative study on the bioactivation mechanisms and toxicity of Te-phenyl-L-tellurocysteine, Se-phenyl-L-selenocysteine, and S-phenyl-L-cysteine.Chem Res Toxicol1516101618PubMedCrossRefGoogle Scholar
  92. Shim, J-Y, Richard, AM 1997Theoretical evaluation of two plausible routes for bioactivation of S-(1,1-difluoro-2,2-dihaloethyl)-L-cysteine conjugates.Chem Res Toxicol10103110PubMedCrossRefGoogle Scholar
  93. Silbernagl S, Heuner A (1993) Renal transport and metabolism of mercapturic acids and their precursors, the S-conjugates of glutathione and cysteine. In: Anders MW, Dekant W, Henschler D, Oberleithner, Silbernagl S (eds) Renal disposition and nephrotoxicity of xenobiotics. Academic Press, San Diego, pp 135–154Google Scholar
  94. Stevens, JL 1985Isolation and characterization of a rat liver enzyme with both cysteine conjugate β lyase and kynureninase activity.J Biol Chem26079457950PubMedGoogle Scholar
  95. Stevens JL, Jones DP (1989) The mercapturic acid pathway: biosynthesis, intermediary metabolism, and physiological disposition. In: Dolphin D, Poulson R, Avramović O (eds) Glutathione: chemical, biochemical and medical aspects, part B. New York, Wiley, pp 45–84Google Scholar
  96. Stevens, JL, Robbins, JD, Byrd, RA 1986A purified cysteine conjugate β-lyase from rat kidney cytosol. Requirement for an α-keto acid or an amino acid oxidase for activity and identity with soluble glutamine transaminase K.J Biol Chem2611552915537PubMedGoogle Scholar
  97. Stockman, S 1916Cases of poisoning in cattle by feeding on soy bean after extraction of the oil.J Comp Pathol2995107Google Scholar
  98. Stoner, GL, Episenberg, MA 1975Purification and properties of 7,8-diaminoperlargonic acid aminotransferase, an enzyme in the biotin biosynthetic pathway.J Biol Chem25040294036PubMedGoogle Scholar
  99. Sweatt, AJ, Garcia-Espinosa, MA, Wallin, R, Hutson, SM 2004Branched-chain amino acids and neurotransmitter metabolism: expression of cytosolic branched-chain aminotransferase (BCATc) in the cerebellum and hippocampus.J Comp Neurol477360370PubMedCrossRefGoogle Scholar
  100. Tateishi, M, Suzuki, S, Shimizu, H 1978Cysteine conjugate β-lyase in rat liver. A novel enzyme catalyzing formation of thiol-containing metabolites of drugs.J Biol Chem25388548859PubMedGoogle Scholar
  101. Teesdale-Spittle, PH, Adcock, HJ, Patterson, LH, Buckberry, LD 1996Rationalisation of the C-S lyase activity of aspartate aminotransferase.Biochem Soc Trans24141SPubMedGoogle Scholar
  102. Tomisawa, H, Ichimoto, N, Ichihara, S, Fukazawa, H, Tateishi, M 1988Involvement of cystathionase in the formation of alkane-thiols from corresponding cysteine conjugates.Xenobiotica1810291037PubMedGoogle Scholar
  103. Toohey, JI 1989Sulphane sulfur in biological systems: a possible regulatory role.Biochem J264625632(Erratum in: Biochem J 267: 843, 1990)PubMedGoogle Scholar
  104. Toohey, JI 2001Possible involvement of sulfane sulfur in homocysteine-induced atherosclerosis.Med Hypotheses56259261PubMedCrossRefGoogle Scholar
  105. Townsend, DM, Deng, M, Zhang, L, Lapus, MG, Hanigan, MH 2003Metabolism of cisplatin to a nephrotoxin in proximal tubule cells.J Am Soc Nephrol14110PubMedCrossRefGoogle Scholar
  106. Ueno, H, Likos, JJ, Metzler, DE 1982Chemistry of inactivation of cytosolic aspartate aminotransferase by serine O-sulfate.Biochemistry2143874393PubMedCrossRefGoogle Scholar
  107. Uttamsingh, V, Baggs, RB, Krenitsky, DM, Anders, MW 2000Immunohistochemical localization of the acylases that catalyze deacylation of N-acetyl-L-cysteine and haloalkene-derived mercapturates.Drug Metab Dispos28625632PubMedGoogle Scholar
  108. Vamvakas, S, Köster, U 1993The nephrotoxin dichlorovinylcysteine induces expression of the protooncogenes c-fos and c-myc in LLC-PK1 cells – a comparative investigation with growth factors and 12 O-tetradecanoylphorbolacetate.Cell Biol Toxicol9113PubMedCrossRefGoogle Scholar
  109. Vamvakas, S, Bittner, D, Köster, U 1993Enhanced expression of the protooncogenes c-myc and c-fos in normal and malignant growth.Toxicol Lett67161172PubMedCrossRefGoogle Scholar
  110. Van Horn, CG, Wallin, R, Fujii, H, Hutson, SM 2004Evidence for a direct protein–protein interaction between the leucine catabolic enzymes.FASEB J1A848(Abstract)Google Scholar
  111. Völkel, W, Dekant, W 1998Chlorothioketene, the ultimate reactive intermediate formed by cysteine conjugate β-lyase-mediated cleavage of the trichloroethene metabolite S-(1,2,-dichlorvinyl)-L-cysteine, forms cytosine adducts in organic solvents, but not in aqueous solution.Chem Res Toxicol1110821088PubMedGoogle Scholar
  112. Wallin, A, Gerdes, RG, Morgenstern, R, Jones, TW, Ormstad, K 1988Features of microsomal and cytosolic glutathione conjugation of hexachlorobutadiene in rat liver.Chem Biol Interact68111PubMedGoogle Scholar
  113. Wolf, CR, Berry, PN, Nash, JA, Lock, EA 1984Role of microsomal and cytosolic glutathione S-transferases in the conjugation of hexachloro-1:3-butadiene and its possible relevance to toxicity.J Pharmacol Exp Ther228202208PubMedGoogle Scholar
  114. Wu, C, Schaum, J 2000Exposure assessment of trichloroethylene.Environ Health Perspect108359363PubMedGoogle Scholar
  115. Xiao, D, Pinto, JT, Soh, J-W, Deguchi, A, Gundersen, GG, Palazzo, AF, Yoon, J-T, Shirin, H, Weinstein, IB 2003Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-jun NH2 terminal kinase 1 activation.Cancer Res6368257837PubMedGoogle Scholar
  116. Yamauchi, A, Stijntjes, GJ, Commandeur, JNM, Vermeulen, NPE 1993Purification of glutamine transaminase K/cysteine conjugate β-lyase from rat renal cytosol based on hydrophobic interaction HPLC and gel permeation FPLC.Protein Expr Purif4552562PubMedGoogle Scholar
  117. Zhang, L, Hanigan, MH 2003Role of cysteine S-conjugate β-lyase in the metabolism of cisplatin.J Pharmacol Exp Ther306988994PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2006

Authors and Affiliations

  • A. J. L. Cooper
    • 1
    • 2
    • 3
  • J. T. Pinto
    • 3
  1. 1.Department of BiochemistryWeill Medical College, Cornell UniversityNew YorkU.S.A.
  2. 2.Department of Neurology and NeuroscienceWeill Medical College, Cornell UniversityNew YorkU.S.A.
  3. 3.Burke Medical Research InstituteWhite PlainsU.S.A.

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