A (Speculative) View on Allicin and Primary Metabolism: An Additional Way to Affect Cell’s Physiology

Author(s): Muhammad Sarfraz, Martin C.H. Gruhlke*

Journal Name: Current Nutraceuticals

Volume 1 , Issue 1 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Allicin from garlic is known for different medical uses for centuries. One important explanation for these effects is the chemical reactivity of allicin as a thiosulfinate towards thiol-groups and the modification of thiol-groups by thioallylation.

Objective: It has been shown that thioallylation can inhibit the enzymatic function of proteins. In different organisms, the thioallylated proteins upon allicin treatment have been examined. It was found, especially in human T-cell lymphocytes (Jurkat-cells), that the glycolysis is a major target for allicin. Here, we briefly discuss that affecting the primary metabolism is a possible part of allicin’s physiological functions and might be, both from therapeutic and nutraceutical view, of particular interest for the application of allicin as an active principle of freshly damaged garlic.

Conclusion: This might, in summary, explain a possible further mode of action of allicin on cells by changing the metabolism as the central life process and thus influencing the overall structure of the physiological processes in the cell, which can lead to the multitude of consequences caused by allicin.

Keywords: Allicin, thioallylation, protein modification, glycolysis, primary metabolism, garlic.

[1]
Borlinghaus, J.; Albrecht, F.; Gruhlke, M.C.; Nwachukwu, I.D.; Slusarenko, A.J. Allicin: chemistry and biological properties. Molecules, 2014, 19(8), 12591-12618.
[http://dx.doi.org/10.3390/molecules190812591] [PMID: 25153873]
[2]
Cavallito, C.J.; Bailey, J.H. Allicin, the antibacterial principle of allium sativum l. isolation, physical properties and antibacterial action. J. Am. Chem. Soc., 1944, 66, 1950-1951.
[http://dx.doi.org/10.1021/ja01239a048]
[3]
Cavallito, C.J.; Buck, J.S.; Suter, C.M. Allicin, the antibacterial principle of Allium sativum. II. Determination of the chemical structure. J. Am. Chem. Soc., 1944, 66, 1952-1954.
[http://dx.doi.org/10.1021/ja01239a049]
[4]
Giles, G.I.; Tasker, K.M.; Jacob, C. Hypothesis: the role of reactive sulfur species in oxidative stress. Free Radic. Biol. Med., 2001, 31(10), 1279-1283.
[http://dx.doi.org/10.1016/S0891-5849(01)00710-9] [PMID: 11705707]
[5]
Gruhlke, M.C.H.; Slusarenko, A.J. The biology of reactive sulfur species (RSS). Plant Physiol. Biochem., 2012, 59, 98-107.
[http://dx.doi.org/10.1016/j.plaphy.2012.03.016] [PMID: 22541352]
[6]
Benavides, G.A.; Squadrito, G.L.; Mills, R.W.; Patel, H.D.; Isbell, T.S.; Patel, R.P.; Darley-Usmar, V.M.; Doeller, J.E.; Kraus, D.W. Hydrogen sulfide mediates the vasoactivity of garlic. Proc. Natl. Acad. Sci. USA, 2007, 104(46), 17977-17982.
[http://dx.doi.org/10.1073/pnas.0705710104] [PMID: 17951430]
[7]
Jacob, C.; Anwar, A. The chemistry behind redox regulation with a focus on sulphur redox systems. Physiol. Plant., 2008, 133(3), 469-480.
[http://dx.doi.org/10.1111/j.1399-3054.2008.01080.x] [PMID: 18346080]
[8]
Block, E. Garlic and Other Alliums - The Lore and the Science, 1st ed; Royal Society of Chemistry: Cambridge, 2010.
[9]
Münchberg, U.; Anwar, A.; Mecklenburg, S.; Jacob, C. Polysulfides as biologically active ingredients of garlic. Org. Biomol. Chem., 2007, 5(10), 1505-1518.
[http://dx.doi.org/10.1039/B703832A] [PMID: 17571177]
[10]
Weber, N.D.; Andersen, D.O.; North, J.A.; Murray, B.K.; Lawson, L.D.; Hughes, B.G. In vitro virucidal effects of Allium sativum (garlic) extract and compounds. Planta Med., 1992, 58(5), 417-423.
[http://dx.doi.org/10.1055/s-2006-961504] [PMID: 1470664]
[11]
Epstein, F.H. Cardiovascular disease epidemiology: a journey from the past into the future. Circulation, 1996, 93(9), 1755-1764.
[http://dx.doi.org/10.1161/01.CIR.93.9.1755] [PMID: 8653883]
[12]
Arditti, F.D.; Rabinkov, A.; Miron, T.; Reisner, Y.; Berrebi, A.; Wilchek, M.; Mirelman, D. Apoptotic killing of B-chronic lymphocytic leukemia tumor cells by allicin generated in situ using a rituximab-alliinase conjugate. Mol. Cancer Ther., 2005, 4(2), 325-331.
[PMID: 15713903]
[13]
Kelsey, N.A.; Wilkins, H.M.; Linseman, D.A. Nutraceutical antioxidants as novel neuroprotective agents. Molecules, 2010, 15(11), 7792-7814.
[http://dx.doi.org/10.3390/molecules15117792] [PMID: 21060289]
[14]
Munday, R.; Munday, J.S.; Munday, C.M. Comparative effects of mono-, di-, tri-, and tetrasulfides derived from plants of the Allium family: redox cycling in vitro and hemolytic activity and Phase 2 enzyme induction in vivo. Free Radic. Biol. Med., 2003, 34(9), 1200-1211.
[http://dx.doi.org/10.1016/S0891-5849(03)00144-8] [PMID: 12706500]
[15]
Roos, G.; Foloppe, N.; Messens, J. Understanding the pK(a) of redox cysteines: the key role of hydrogen bonding. Antioxid. Redox Signal., 2013, 18(1), 94-127.
[http://dx.doi.org/10.1089/ars.2012.4521] [PMID: 22746677]
[16]
Wills, E.D. Enzyme inhibition by allicin, the active principle of garlic. Biochem. J., 1956, 63(3), 514-520.
[http://dx.doi.org/10.1042/bj0630514] [PMID: 13341914]
[17]
Kubec, R.; Hrbácová, M.; Musah, R.A.; Velísek, J. Allium discoloration: precursors involved in onion pinking and garlic greening. J. Agric. Food Chem., 2004, 52(16), 5089-5094.
[http://dx.doi.org/10.1021/jf0497455] [PMID: 15291480]
[18]
Cho, J.; Lee, E.J.; Yoo, K.S.; Lee, S.K.; Patil, B.S. Identification of candidate amino acids involved in the formation of blue pigments in crushed garlic cloves (Allium sativum L.). J. Food Sci., 2009, 74(1), C11-C16.
[http://dx.doi.org/10.1111/j.1750-3841.2008.00986.x] [PMID: 19200080]
[19]
Gupta, N.; Porter, T.D. Garlic and garlic-derived compounds inhibit human squalene monooxygenase. J. Nutr., 2001, 131(6), 1662-1667.
[http://dx.doi.org/10.1093/jn/131.6.1662] [PMID: 11385050]
[20]
Focke, M.; Feld, A.; Lichtenthaler, K. Allicin, a naturally occurring antibiotic from garlic, specifically inhibits acetyl-CoA synthetase. FEBS Lett., 1990, 261(1), 106-108.
[http://dx.doi.org/10.1016/0014-5793(90)80647-2] [PMID: 1968399]
[21]
Focke, M.; Feld, A.; Lichtenthaler, H.K. Inhibition of early steps of de novo fatty-acid biosynthesis by different xenobiotica. Physiol. Plant., 1991, 81(2), 251-255.
[http://dx.doi.org/10.1111/j.1399-3054.1991.tb02138.x]
[22]
Gruhlke, M.C.H.; Antelmann, H.; Bernhardt, J.; Kloubert, V.; Rink, L.; Slusarenko, A.J. The human allicin-proteome: S-thioallylation of proteins by the garlic defence substance allicin and its biological effects. Free Radic. Biol. Med., 2019, 131, 144-153.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.022] [PMID: 30500420]
[23]
Horn, T.; Bettray, W.; Slusarenko, A.J.; Gruhlke, M.C.H. S-allylmer-captoglutathione is a substrate for glutathione reductase (E.C. 1.8.1.7) from yeast (Saccharomyces cerevisiae). Antioxidants, 2018, 7(7) E86
[http://dx.doi.org/10.3390/antiox7070086] [PMID: 29986384]
[24]
Leontiev, R.; Hohaus, N.; Jacob, C.; Gruhlke, M.C.H.; Slusarenko, A.J. A Comparison of the antibacterial and antifungal activities of thiosulfinate analogues of allicin. Sci. Rep., 2018, 8(1), 6763.
[http://dx.doi.org/10.1038/s41598-018-25154-9] [PMID: 29712980]
[25]
Müller, A.; Eller, J.; Albrecht, F.; Prochnow, P.; Kuhlmann, K.; Bandow, J.E.; Slusarenko, A.J.; Leichert, L.I. HYPERLINK. "http://dx.doi.org/10.1074/jbc.M115.702308" allicin induces thiol stress in bacteria through S-Allylmercapto modification of protein cysteines. J. Biol. Chem., 2016, 291(22), 11477-11490.
[http://dx.doi.org/10.1074/jbc.M115.702308] [PMID: 27008862]
[26]
Loi, V.V.; Huyen, N.T.T.; Busche, T.; Tung, Q.N.; Gruhlke, M.C.H.; Kalinowski, J.; Bernhardt, J.; Slusarenko, A.J.; Antelmann, H. Staphylococcus aureus responds to allicin by global S-thioallylation - Role of the Brx/BSH/YpdA pathway and the disulfide reductase MerA to overcome allicin stress. Free Radic. Biol. Med., 2019, 139, 55-69.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.05.018] [PMID: 31121222]
[27]
Reiter, J.; Hübbers, A.M.; Albrecht, F.; Leichert, L.I.O.; Slusarenko, A.J. Allicin, a natural antimicrobial defence substance from garlic, inhibits DNA gyrase activity in bacteria. Int. J. Med. Microbiol., 2019, 310(1), 15. 1359.
[http://dx.doi.org/10.1016/j.ijmm.2019.151359] [PMID: 31585716]
[28]
Reiter, J.; Levina, N.; van der Linden, M.; Gruhlke, M.; Martin, C.; Slusarenko, A.J. Diallylthiosulfinate (Allicin), a volatile antimicrobial from garlic (Allium sativum), kills human lung pathogenic bacteria, including MDR strains, as a vapor. Molecules, 2017, 22(10), 1711.
[http://dx.doi.org/10.3390/molecules22101711] [PMID: 29023413]


promotion: free to download

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 1
ISSUE: 1
Year: 2020
Page: [14 - 17]
Pages: 4
DOI: 10.2174/2665978601666200228092006

Article Metrics

PDF: 13
HTML: 2
EPUB: 1
PRC: 1