Ci. Chien et al., ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS - INHIBITION OF RAT-LIVER GLUTATHIONE-S-TRANSFERASE ISOZYMES AND CHEMICAL-REACTION WITH REDUCED GLUTATHIONE, Biochimica et biophysica acta. Protein structure and molecular enzymology, 1204(2), 1994, pp. 175-180
Five different alpha,beta-unsaturated carbonyl compounds displayed dif
ferent reactivities with regard to inhibition of alpha- and mu-class i
sozymes of rat liver glutathione S-transferases and the chemical react
ion with glutathione. Only (E)-2-octenal and (E)-3-nonen-2-one exhibit
ed significant levels of inhibition for each of the rat liver GST isoz
ymes examined. The (E)-2-octenal was more effective as an inhibitor of
the alpha-class of isozymes when compared to the mu-class, whereas th
e (E)-3-nonen-2-one showed a greater degree of inhibition of the mu-cl
ass of isozymes relative to the alpha-class. Isozyme 1-1 demonstrated
the greatest degree of inhibition with (E)-2-octenal (IC50 = 5.89 mu M
) of air inhibitor/isozyme combinations. The K-i values for (E)-2-octe
nal and (E)3-nonen-2-one toward selected mu-and mu-class of rat liver
glutathione S-transferase isozymes were determined and both of these c
ompounds competitively inhibited all five of the rat liver glutathione
S-transferase isozymes examined. The K-i values obtained for these tw
o compounds were significantly different for each of the isozymes exce
pt for isozyme 4-4. With the alpha-class of rat liver GST isozymes, (E
)-3-nonen-2-one showed a larger K-i value than (E)-2-octenal. Whereas,
with the mu-class, (E)-2-octenal exhibited a larger K-i value than (E
)-3-nonen-2-one. The rate constants of the forward reaction (k(+1)), a
s well as the equilibrium constants (K-d) were determined and the rate
constants of the reverse reaction (k(-1)) were calculated.