The C-S lysis of L-cysteine conjugates by aspartate and alanine aminotransferase enzymes.
One biotransformation pathway which is responsible for the generation of mutagenic and cytotoxic metabolites is that of the C-S lysis (CSL) of L-cysteine conjugates. Thirteen cysteine S-conjugates, synthesised in our laboratories, were incubated with porcine heart aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT), and the C-S lyase activity for each enzyme-substrate combination was determined. ASAT and ALAT were shown to exhibit CSL activity. It was also demonstrated that this activity was inhibited in the presence of the pyridoxal phosphate (PLP)-dependent enzyme inhibitor amino(oxyacetic acid) (AOAA) confirming the pyridoxal phosphate dependent mechanism by which C-S lysis is known to take place. Since the activities of these enzymes are used as biomarkers for the assessment of organ damage, the potential interaction of L-cysteine conjugates with them may suppress their activity through direct inhibition.
Gaskin
P J
PJ
Department of Pharmaceutical Sciences, University of Nottingham, UK.
Adcock
H J
HJ
Buckberry
L D
LD
Teesdale-Spittle
P H
PH
Shaw
P N
PN
D000410:Alanine Transaminase / Q000378:metabolism*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001711:Biotransformation; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D013552:Swine
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003545:Cysteine