S-Allylmercaptoglutathione: the reaction product of allicin with glutathione possesses SH-modifying and antioxidant properties

The reaction between allicin (diallylthiosulfinate), the active component o f garlic and reduced glutathione was investigated. The product of this reac tion, mixed disulfide S-allylmercaptoglutathione (GSSA) was separated by hi gh performance liquid chromatography and identified by H-1 and C-13 nuclear magnetic resonance and mass spectroscopy. The reaction is fast (with an ap parent bimolecular reaction rate constant of 3.0 M-1 s(-1)). It is pH-depen dent, which reveals a direct correlation to the actual concentration of mer captide ion (GS(-)). Both GSSA and S-allylmercaptocysteine (prepared from a llicin and cysteine) reacted with SH-containing enzymes, papain and alcohol dehydrogenase from Thermoanaerobium brockii yielding the corresponding S-a llylmercapto proteins, and caused inactivation of the enzymes. The activity was restored with dithiothreitol or 2-mercaptoethanol. In addition, GSSA a lso exhibited high antioxidant properties. It showed significant inhibition of the reaction between OH radicals and the spin trap 5,5'-dimethyl-1-pyro line N-oxide in the Fenton system as well as in the UV photolysis of H2O2. In ex vivo experiments done with fetal brain slices under iron-induced oxid ative stress, GSSA significantly lowered the production levels of lipid per oxides. The similar activity of GSSA and allicin as SH-modifiers and antiox idants suggests that the thioallyl moiety has a key role in the biological activity of allicin and its derivatives. (C) 2000 Elsevier Science B.V. All rights reserved.