Reaction of glutathione with conjugated carbonyls

1. GSH reacts with conjugated carbonyls according to the equation: GSH+R-CH=CH-COR in equilibrium R-CH(SG)-CH2-COR. The forward reaction follows second order, the reverse reaction first order kinetics. It is assumed that this reaction reflects best the ability of conjugated carbonyls to inactivate SH groups in biological systems. 2. The rate of forward reaction increases with pH approx. parallel with alphaSH. Besides OH- ions also proton donors (e.g. buffers) increase the rate. The catalytic effect of pH and buffer is interpreted in view of the reaction mechanism. 3. The equilibrium constants as well as the rate constants for forward (k1) and reverse reaction show an extreme variation depending on the carbonyl structure. Acrolein and methyl vinyl ketone (k1 = 120 and 32 mol-1 sec-1, resp.) react more rapidly than any other carbonyl to give very stable adducts (half-lives for reverse reaction 4.6 and 60.7 days, resp). Somewhat less reactive are 4-hydroxy-2-alkenals and 4-ketopentenoic acid (k1 between 1 and 3 mol-1 sec-1), but they also form very stable adducts showing half-lives between 3.4 and 19 days. All other carbonyl studied react either very slowly (e.g. citral, ethly crotonate, mesityl oxide, acrylic acid) or form very labile adducts (crotonal, pentenal, hexenal, 3-methyl-butenone). Comparing biological activities of conjugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered.