Redox-sensitive proteins are potential targets of garlic-derived mercaptocysteine derivatives.
Review
Overview
abstract
Molecular investigations support existing clinical and epidemiological data that garlic-derived allylsulfides reduce cancer risk. Various allylsulfides can diminish progression of cancer cells at either the G1/S or G2/M phase. Allylsulfide derivatives modify redox-sensitive signal pathways and cause growth inhibition, mitotic arrest, and apoptosis induction. Whether allylsulfides modify intracellular redox potentials by affecting the ratio of glutathione:glutathione disulfide and/or by interacting directly with sulfhydryl domains on regulatory or catalytic-signal proteins requires further investigation. To understand the possible biochemical mechanisms contributing to the protective effects of allylsulfides, we investigated the ability of these compounds to undergo enzyme-catalyzed transformations. In addition to catalyzing gamma-elimination reactions, gamma-cystathionase can perform beta-elimination reactions with cysteinyl S-conjugates derived from garlic extracts when the S-alkyl group (R) is larger than ethyl. The reaction products are pyruvate, ammonium, and a sulfur-containing fragment (RSH). beta-Lyase substrates of gamma-cystathionase thus far identified from garlic include: S-allyl-L-cysteine (R=CH2=CHCH2-), S-allylmercapto-L-cysteine (R=CH2=CHCH2S-), and S-propylmercapto-L-cysteine (R=CH3CH2CH2S-). Mercapto derivatives yield persulfide products (RSSH) that are potential sources of sulfane sulfur, which may modify protein function by reacting at important cysteinyl domains. Thus, beta-elimination reactions with cysteine S-conjugates in garlic may modify cancer-cell growth by targeting redox-sensitive signal proteins at sulfhydryl sites, thereby regulating cell proliferation and/or apoptotic responses. These interactions may be useful in identifying efficacy of garlic-derived compounds and/or developing other novel organosulfur compounds that may modify intracellular redox potentials or interact with thiols associated within cysteine domains in regulatory, catalytic, signal, or structural proteins.
