S-Allylmercaptoglutathione: the reaction product of allicin with glutathione possesses SH-modifying and antioxidant properties.
The reaction between allicin (diallylthiosulfinate), the active component of garlic and reduced glutathione was investigated. The product of this reaction, mixed disulfide S-allylmercaptoglutathione (GSSA) was separated by high performance liquid chromatography and identified by 1H and (13)C nuclear magnetic resonance and mass spectroscopy. The reaction is fast (with an apparent bimolecular reaction rate constant of 3.0 M(-1) s(-1)). It is pH-dependent, which reveals a direct correlation to the actual concentration of mercaptide ion (GS(-)). Both GSSA and S-allylmercaptocysteine (prepared from allicin and cysteine) reacted with SH-containing enzymes, papain and alcohol dehydrogenase from Thermoanaerobium brockii yielding the corresponding S-allylmercapto proteins, and caused inactivation of the enzymes. The activity was restored with dithiothreitol or 2-mercaptoethanol. In addition, GSSA also exhibited high antioxidant properties. It showed significant inhibition of the reaction between OH radicals and the spin trap 5,5'-dimethyl-1-pyroline 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 oxidative stress, GSSA significantly lowered the production levels of lipid peroxides. The similar activity of GSSA and allicin as SH-modifiers and antioxidants suggests that the thioallyl moiety has a key role in the biological activity of allicin and its derivatives.
Rabinkov
A
A
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Miron
T
T
Mirelman
D
D
Wilchek
M
M
Glozman
S
S
Yavin
E
E
Weiner
L
L
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000975:Antioxidants / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004220:Disulfides; D004791:Enzyme Inhibitors / Q000737:chemistry; D005737:Garlic; D005978:Glutathione / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010206:Papain / Q000037:antagonists & inhibitors; D010946:Plants, Medicinal; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013441:Sulfinic Acids / Q000737:chemistry*
D000975:Antioxidants; D004220:Disulfides; D004791:Enzyme Inhibitors; C086300:S-allylmercaptocysteine; D013438:Sulfhydryl Compounds; D013441:Sulfinic Acids; C006452:allicin; D000426:Alcohol Dehydrogenase; D010206:Papain; D005978:Glutathione; D003545:Cysteine