Novel sources of mammalian C-S lyase activity.
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.
Adcock
H J
HJ
Department of Chemistry, De Montfort University, Leicester, UK.
Gaskin
P J
PJ
Shaw
P N
PN
Teesdale-Spittle
P H
PH
Buckberry
L D
LD
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
C039961:S-(1,2-dichlorovinyl)cysteine; D003547:Cysteine Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003545:Cysteine