Corpus ID: 44306710

Alpha-ketoacids stimulate rat renal cysteine conjugate beta-lyase activity and potentiate the cytotoxicity of S-(1,2-dichlorovinyl)-L-cysteine.

  title={Alpha-ketoacids stimulate rat renal cysteine conjugate beta-lyase activity and potentiate the cytotoxicity of S-(1,2-dichlorovinyl)-L-cysteine.},
  author={A. Elfarra and L. Lash and M. W. Anders},
  journal={Molecular pharmacology},
  volume={31 2},
Renal cysteine conjugate beta-lyase (beta-lyase) catalyzes the bioactivation of nephrotoxic cysteine S-conjugates. beta-Lyase activity is present in both renal cytosolic and mitochondrial fractions, and, although the cytosolic beta-lyase is identical to glutamine transaminase K, the mitochondrial beta-lyase has not been characterized. Because beta-lyase is a pyridoxal phosphate (PLP)-dependent enzyme, pyridoxamine phosphate (PMP) formation may occur during the metabolism of cysteine S… Expand
Cysteine conjugate beta-lyase activity of rat erythrocytes and formation of beta-lyase-derived globin monoadducts and cross-links after in vitro exposure of erythrocytes to S-(1,2-dichlorovinyl)-L-cysteine.
The results suggested that erythrocytes have beta-lyase but not S-oxidase activity, and further support for this hypothesis was obtained using S-(2-benzothiazolyl)-L-cysteine, an alternative substrate forbeta-lyases. Expand
Human mitochondrial and cytosolic branched-chain aminotransferases are cysteine S-conjugate beta-lyases, but turnover leads to inactivation.
The present results suggest that BCAT isozymes may contribute to the mitochondrial toxicity of these compounds by providing thioacylating fragments, but inactivation of the BCATIsozymes might also block essential metabolic pathways. Expand
Glutamine transaminase K and cysteine S-conjugate β-lyase activity stains
Activity staining showed that homogenates of rat kidney, liver, skeletal muscle, and heart possess a glutamine transaminase K/cysteine S-conjugate beta-lyase activity with an Rf value identical to that of purified rat kidney glutamines transaminases K. Expand
High Activities of Glutamine Transaminase K (Dichlorovinylcysteine β‐Lyase) and ω‐Amidase in the Choroid Plexus of Rat Brain
It is shown that with dichlorovinylcysteine as substrate the only detectable cysteine‐S‐conjugate β‐lyase in rat brain homogenates is identical to glutamine transaminase K, and that any explanation of the neurotoxicity of halogenated xenobiotics must take into account the role of glutamines transaminases K and its presence in the choroid plexus. Expand
Role of renal metabolism in risk to toxic chemicals.
  • L. Lash
  • Chemistry, Medicine
  • Environmental health perspectives
  • 1994
Findings show that mammalian kidney is highly active in bioactivation of xenobiotics, and clear that renal metabolism can be a critical determinant of risk to chemical injury. Expand
The role of glutamine transaminase K (GTK) in sulfur and α-keto acid metabolism in the brain, and in the possible bioactivation of neurotoxicants
It is discussed that the spontaneous hypertension in rats carrying the GTK/KAT I mutation may be due in part to disruption of glutamine transamination, and one of several pyridoxal 5'-phosphate (PLP)-containing enzymes that can catalyze non-physiological beta-elimination reactions with cysteine S-conjugates containing a good leaving group attached at the sulfur. Expand
Mitochondrial bioactivation of cysteine S-conjugates and 4-thiaalkanoates: implications for mitochondrial dysfunction and mitochondrial diseases.
  • M. W. Anders
  • Biology, Medicine
  • Biochimica et biophysica acta
  • 1995
Mitochondrial dysfunction is the hallmark of cysteine S-conjugate-induced cytotoxicity: decreased respiration, decreased ATP and total adenine nucleotide concentrations, depletion of the mitochondrial glutathione content, perturbations in cellular Ca2+ homeostasis, and damage to the mitochondrial genome are seen. Expand
Bioactivation mechanism of cytotoxic homocysteine S-conjugates.
The data indicate that the bioactivation of homocysteine S-conjugates and analogs involves the enzymatic formation of the corresponding 2-oxo acids followed by a nonenzymatic retro-Michael elimination reaction to yield the Michael acceptor 2-Oxo-3-butenoic acid, which may contribute to the observed cytotoxicity of homocytes. Expand
Beta-lyase-dependent attenuation of cisplatin-mediated toxicity by selenocysteine Se-conjugates in renal tubular cell lines.
The results indicate that all three selenocysteine Se-conjugates were able to attenuate the cisplatin-induced loss of viability in R1J cells but not in the parental LLC-PK(1) cells, further supporting the role of beta-lyase in the observed chemoprotection. Expand
Purification and characterization of cysteine conjugate transaminases from rat liver.
Soluble cysteine-conjugate alpha-ketoglutarate transaminase (CAT-I) was purified from rat liver cytosol using s-(p-bromophenyl)-L-cysteine as amino acid substrate and two isozymes were very similar to CAT-I, however, differences were observed for these enzymes in the rate of reverse reaction and substrate specificity towards L-aspartic acid and L- Cysteinesulphinic acid. Expand