title: Novel sources of mammalian C-S lyase activity.
abstract: The C-S lysis of L-cysteine conjugates is one biotransformation pathway which is responsible for the generation of mutagenic and cytotoxic metabolic species. Thirteen cysteine S-conjugates were synthesized in our laboratories and incubated with aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) enzymes from porcine heart tissue. The C-S lyase (CSL) activity for each enzyme-substrate combination was determined. ASAT and ALAT were shown to exhibit CSL activity and it was also demonstrated that this activity was inhibited in the presence of the pyridoxal phosphate-dependent enzyme inhibitor amino(oxyacetic acid) confirming the pyridoxal phosphate-dependent mechanism by which C-S lysis is known to take place. This finding has potentially important implications for the risk assessment of compounds which produce L-cysteine conjugates during their biotransformation.
authors.affiliation: Department of Chemistry, De Montfort University, Leicester, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Adcock
authors.forename: P J
authors.initials: PJ
authors.lastname: Gaskin
authors.forename: P N
authors.initials: PN
authors.lastname: Shaw
authors.forename: P H
authors.initials: PH
authors.lastname: Teesdale-Spittle
authors.forename: L D
authors.initials: LD
authors.lastname: Buckberry
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001711:Biotransformation; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D003547:Cysteine Synthase / Q000493:pharmacokinetics*; D008958:Models, Molecular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine
chemical_list: C039961:S-(1,2-dichlorovinyl)cysteine; D003547:Cysteine Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003545:Cysteine