Inhibition of rat liver cytosolic glutathione S-transferase by silybin.
1. The naturally occurring hepatoprotective compound silybin is a potent inhibitor of glutathione S-transferase isoenzymes 1-1, 2-2, 3-3, and 4-4, displaying a high degree of isoenzyme selectivity. 2. Using CDNB at a fixed concentration of 1 mM and varying the GSH concentration, silybin exhibited competitive inhibition of isoenzyme 2-2 with a Ki of 32 microM, non-competitive and predominantly non-competitive inhibition of isoenzymes 1-1 and 4-4 with Kis of 20 and 1.2 microM, respectively, and uncompetitive inhibition of isoenzyme 3-3 with a Ki of 0.2 microM. 3. With CDNB as the variable concentration substrate silybin exhibited competitive inhibition of isoenzyme 1-1 with a Ki of 8 microM, non-competitive inhibition of isoenzyme 2-2 with a Ki of 41 microM, and non-competitive inhibition of isoenzymes 3-3 and 4-4 with Kis of 0.8 and 0.5 microM, respectively.
Bartholomaeus
A R
AR
Key Centre for Applied and Nutritional Toxicology, RMIT-University, Melbourne, Australia.
Bolton
R
R
Ahokas
J T
JT
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004137:Dinitrochlorobenzene; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*
D004137:Dinitrochlorobenzene; D007527:Isoenzymes; D012838:Silymarin; D005982:Glutathione Transferase; D005978:Glutathione