Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme.
The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate.
Buckberry
L D
LD
Department of Pharmaceutical Sciences, University of Nottingham, UK.
Blagbrough
I S
IS
Bycroft
B W
BW
Shaw
P N
PN
D000328:Adult; D013437:Carbon-Sulfur Lyases; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007526:Isoelectric Point; D008099:Liver / Q000201:enzymology*; D008190:Lyases / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008970:Molecular Weight; D011247:Pregnancy; D012967:Sodium Dodecyl Sulfate; D000637:Transaminases / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology
D012967:Sodium Dodecyl Sulfate; C039961:S-(1,2-dichlorovinyl)cysteine; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C019969:S-alkylcysteine lyase; D003545:Cysteine