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 K-i of 32 mu M, noncompetitive and predominantly non-competitive inhibition of isoenzymes 1-1 and 4-4 with K(i)s of 20 and 1.2 mu M, respectively, and uncompetitive inhibition of isoenzyme 3-3 with a K-i of 0.2 mu M. 3. With CDNB as the variable concentration substrate silybin exhibited competitive inhibition of isoenzyme 1-1 with a K-i of 8 mu M, non-competitive inhibition of isoenzyme 2-2 with a K-i of 41 mu M, and non-competitive inhibition of isoenzymes 3-3 and 4-4 with K(i)s of 0.8 and 0.5 mu M, respectively.