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Abstract
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 32μM, non-competitive and predominantly non-competitive inhibition of isoenzymes 1-1 and 4-4 with Kis of 20 and 1·2 μM, respectively, and uncompetitive inhibition of isoenzyme 3-3 with a Ki of 0·2 μM.
3. With CDNB as the variable concentration substrate silybin exhibited competitive inhibition of isoenzyme 1-1 with a Ki of 8 μM, non-competitive inhibition of isoenzyme 2-2 with a Ki of 41 μM, and non-competitive inhibition of isoenzymes 3-3 and 4-4 with Kis of 0·8 and 0·5 μM, respectively.
