Redox-sensitive proteins are potential targets of garlic-derived mercaptocysteine derivatives.
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.
Burke Medical Research Institute, White Plains, NY 10605, USA. jpinto@burke.org
John T
JT
Pinto
Boris F
BF
Krasnikov
Arthur J L
AJ
Cooper
D000818:Animals; D015179:Colorectal Neoplasms / Q000517:prevention & control; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D005737:Garlic; D006801:Humans; D023421:Models, Animal; D010084:Oxidation-Reduction; D010936:Plant Extracts; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000517:prevention & control
D010936:Plant Extracts; D011506:Proteins; C086300:S-allylmercaptocysteine; D003545:Cysteine