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REHOVOT, Israel - October 14, 1997 - Garlic is believed to work wonders, from fighting disease to keeping away vampires. Now two studies conducted at the Weizmann Institute of Science have uncovered a molecular mechanism which may be the basis for some of garlic's therapeutic effects.
The researchers were able to study how garlic works at the molecular level thanks to their unique biotechnological procedure for producing large quantities of pure allicin, garlic's main biologically active component.
One study, appearing in the October issue of the American Society for Microbiology's Antimicrobial Agents and Chemotherapy , explains how allicin fights infection. This research supports the notion that garlic is an excellent, although smelly, natural antimicrobial drug that can disable an unusually wide variety of infectious organisms.
The second study, soon to be reported in Biochimica Biophysica Acta, may help clarify the role allicin plays in preventing heart disease and other disorders.
In the studies, the scientists revealed and characterized a molecular mechanism by which allicin blocks certain groups of enzymes.
Allicin, created when garlic cloves are crushed, protects the plant from soil parasites and fungi and is also responsible for garlic's pungent smell.
The studies were led by Profs. David Mirelman and Meir Wilchek of the Institute's Biological Chemistry Department, who worked together with departmental colleagues Drs. Serge Ankri, Talia Miron and Aharon Rabinkov and with Prof. Lev Weiner and Dr. Leonid Konstantinovski of the Organic Chemistry Department.
Cysteine proteinase enzymes are among the main culprits in infection, providing infectious organisms with the means to damage and invade tissues. Alcohol dehydrogenase enzymes play a major role in these harmful organisms' metabolism and survival.
Because these groups of enzymes are found in a wide variety of infectious organisms such as bacteria, fungi and viruses, this research provides a scientific basis for the notion that allicin is a broad-spectrum antimicrobial drug, capable of warding off different types of infections.
"It has long been argued that garlic can fight a wide range of infections, and now we have provided biochemical evidence for this claim," says Prof. Mirelman.
The role of allicin in warding off infection may be particularly valuable in light of the growing bacterial resistance to antibiotics. It is unlikely that bacteria would develop resistance to allicin because this would require modifying the very enzymes that make their activity possible.
This finding has important implications because sulfhydryl groups are also crucial components of some enzymes that participate in the synthesis of cholesterol. By reacting with and modifying the sulfhydryl groups in those enzymes, allicin may prevent the production of artery-clogging cholesterol.
"It has been suggested that garlic lowers the levels of harmful cholesterol, and our study provides a possible explanation for how this may occur," says Prof. Wilchek. "However, more research is necessary to establish what role allicin might play in preventing the clogging up of arteries."
Complicating the issue is the concern that blocking sulfhydryl groups in proteins may sometimes be harmful because these groups are also present in enzymes involved in some of the body's vital processes. However, unlike most bacteria, human tissue cells contain detoxifying molecules of a substance called glutathione, which helps maintain appropriate sulfhydryl levels. These glutathione molecules can reverse the anti-sulfhydryl effects of small amounts of allicin.
The allicin produced at the Weizmann Institute is semi-synthetic; first, its precursor, alliin, is chemically synthesized, then a modified form of the natural enzyme, alliinase, converts it into pure allicin.The pure semi-synthetic allicin can be stored for months without losing its effectiveness. In contrast, the natural compound loses its beneficial properties within hours because it begins to react with garlic's other components as soon as the clove is crushed.
A patent application for this production of pure allicin has been submitted by Yeda Research and Development Co., the Institute's technology transfer arm, and several companies have already expressed interest in scaling up the process for commercial use and clinical testing.
Prof. Mirelman, the Weizmann Institute's Vice President for Technology Transfer, holds the Besen-Brender Chair of Microbiology and Parasitology, and Prof. Wilchek, Dean of the Biochemistry Faculty, holds the Marc R. Gutwirth Chair of Molecular Biology.
This research was funded in part by the Center for Molecular Biology of Tropical Diseases at the Weizmann Institute and the Avicenne Program of the European Union. Drs. Rabinkov and Konstantinovski were partly supported by the Center for the Absorption of Scientists of Israel's Ministry of Absorption.
The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
The researchers were able to study how garlic works at the molecular level thanks to their unique biotechnological procedure for producing large quantities of pure allicin, garlic's main biologically active component.
One study, appearing in the October issue of the American Society for Microbiology's Antimicrobial Agents and Chemotherapy , explains how allicin fights infection. This research supports the notion that garlic is an excellent, although smelly, natural antimicrobial drug that can disable an unusually wide variety of infectious organisms.
The second study, soon to be reported in Biochimica Biophysica Acta, may help clarify the role allicin plays in preventing heart disease and other disorders.
In the studies, the scientists revealed and characterized a molecular mechanism by which allicin blocks certain groups of enzymes.
Allicin, created when garlic cloves are crushed, protects the plant from soil parasites and fungi and is also responsible for garlic's pungent smell.
The studies were led by Profs. David Mirelman and Meir Wilchek of the Institute's Biological Chemistry Department, who worked together with departmental colleagues Drs. Serge Ankri, Talia Miron and Aharon Rabinkov and with Prof. Lev Weiner and Dr. Leonid Konstantinovski of the Organic Chemistry Department.
A natural weapon against infection
The research reported in October's Antimicrobial Agents and Chemotherapy revealed that allicin disables dysentery-causing amoebas by blocking two groups of enzymes, cysteine proteinases and alcohol dehydrogenases.
Cysteine proteinase enzymes are among the main culprits in infection, providing infectious organisms with the means to damage and invade tissues. Alcohol dehydrogenase enzymes play a major role in these harmful organisms' metabolism and survival.
Because these groups of enzymes are found in a wide variety of infectious organisms such as bacteria, fungi and viruses, this research provides a scientific basis for the notion that allicin is a broad-spectrum antimicrobial drug, capable of warding off different types of infections.
"It has long been argued that garlic can fight a wide range of infections, and now we have provided biochemical evidence for this claim," says Prof. Mirelman.
The role of allicin in warding off infection may be particularly valuable in light of the growing bacterial resistance to antibiotics. It is unlikely that bacteria would develop resistance to allicin because this would require modifying the very enzymes that make their activity possible.
Blocking mechanism explained
In the study slated to appear in Biochimica Biophysica Acta, Institute scientists found that allicin blocks the enzymes by reacting with one of their important components known as sulfhydryl (SH) groups, or thiols.
This finding has important implications because sulfhydryl groups are also crucial components of some enzymes that participate in the synthesis of cholesterol. By reacting with and modifying the sulfhydryl groups in those enzymes, allicin may prevent the production of artery-clogging cholesterol.
"It has been suggested that garlic lowers the levels of harmful cholesterol, and our study provides a possible explanation for how this may occur," says Prof. Wilchek. "However, more research is necessary to establish what role allicin might play in preventing the clogging up of arteries."
Complicating the issue is the concern that blocking sulfhydryl groups in proteins may sometimes be harmful because these groups are also present in enzymes involved in some of the body's vital processes. However, unlike most bacteria, human tissue cells contain detoxifying molecules of a substance called glutathione, which helps maintain appropriate sulfhydryl levels. These glutathione molecules can reverse the anti-sulfhydryl effects of small amounts of allicin.
Measuring antioxidant activity
While reaction with sulfhydryl groups appears to explain most of allicin's activity, it has also been suggested that allicin acts as an antioxidant. The study reported in BBA confirmed this antioxidant effect and for the first time provided its quantitative assessment. Antioxidants gobble up harmful free radicals believed to contribute to tumor growth, atherosclerosis, aging and other processes.
Producing pure allicin in large quantities
In nature, allicin is created when garlic cloves are cut into or crushed. The cutting or crushing causes two components of garlic, alliin and the enzyme alliinase, to interact.
The allicin produced at the Weizmann Institute is semi-synthetic; first, its precursor, alliin, is chemically synthesized, then a modified form of the natural enzyme, alliinase, converts it into pure allicin.The pure semi-synthetic allicin can be stored for months without losing its effectiveness. In contrast, the natural compound loses its beneficial properties within hours because it begins to react with garlic's other components as soon as the clove is crushed.
A patent application for this production of pure allicin has been submitted by Yeda Research and Development Co., the Institute's technology transfer arm, and several companies have already expressed interest in scaling up the process for commercial use and clinical testing.
Prof. Mirelman, the Weizmann Institute's Vice President for Technology Transfer, holds the Besen-Brender Chair of Microbiology and Parasitology, and Prof. Wilchek, Dean of the Biochemistry Faculty, holds the Marc R. Gutwirth Chair of Molecular Biology.
This research was funded in part by the Center for Molecular Biology of Tropical Diseases at the Weizmann Institute and the Avicenne Program of the European Union. Drs. Rabinkov and Konstantinovski were partly supported by the Center for the Absorption of Scientists of Israel's Ministry of Absorption.
The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
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