Although hundreds of scientific papers have been published in the past three decades reporting a variety of medicinal values of garlic-derived organosulfur compounds, the physiological fate of these compounds and their specific biochemical/biological effects are still poorly understood. The first objective of this project is to synthesize some [35S] labeled garlic-derived organosulfur compounds, such as S-allyl-L- cysteine sulfoxide(alliin), daillyl thiosulfinate (allicin), S- allylmercaptocysteine, allyl mercaptan, diallyl disulfide, diallyl trisulfide, gamma-glutamyl-S-allylcysteine, and (E)-ajoene and (Z)- ajoene. These labeled compounds will be used to investigate their biochemical fate in the blood and tissue homogenates and their interaction with some enzymes and proteins. They will also be used by a collaborator from another institution to investigate their physiological fate in the blood and tissues after administration to the animals by intragastric intubation. The second objective of this study is to examine the hypothesis proposed by some leading researchers in this field that garlic-derived organosulfur compounds may exert their biological effects by modifying the essential sulfhydryl (SH) groups of some enzymes or proteins. The sulfhydryl enzymes to be studied will at least include glutathione-S-transferase, glyceraldehyde-3P dehydrogenase, fructose-1,6-bisphosphatase, phosphofructokinase, xanthine oxidase, and alcohol dehydrogenase, since these enzymes all contain reactive essential SH groups. The third objective is to investigate whether the SH groups of tissues (nonprotein and protein-bound SH groups) will be altered after consuming garlic or garlic products (this may reflect whether the redox states of tissues are altered). The fourth objective is to investigate the potential biological effect of allyl mercaptan, which is the dominant sulfur compound found in the blood after consuming garlic or garlic products. The focus will be placed on its potential reducing or anti- oxidant effect. The mechanism for rapid formation of allyl mercaptan in blood after addition of allicin or S-allymercaptocysteine will also be investigated. This study may yield information valuable to the understanding of the physiological fate of garlic-derived organosulfur compounds and the ultimate specific compounds that are responsible for their various biological effects.
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