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{{distinguish|Tomatin|thaumatin}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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{{chembox |
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{{chembox |
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| verifiedrevid = 416363305 |
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| verifiedrevid = 470611763 |
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| Name = α-Tomatine |
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| Name = α-tomatine |
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| ImageFile =alpha-Tomatine.png |
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| ImageFile = Alpha-Tomatine.svg |
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| ImageSize = 250px |
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| ImageSize = 250px |
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| IUPACName = (22''S'',25''S'')-5α-spirosolan-3β-yl β-<small>D</small>-glucopyranosyl-(1→2)--β-<small>D</small>-glucopyranosyl-(1→4)-β-<small>D</small>-galactopyranoside |
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| IUPACName = (22''S'',25''S'')-5α-spirosolan-3β-yl β-<small>D</small>-glucopyranosyl-(1→2)--β-<small>D</small>-glucopyranosyl-(1→4)-β-<small>D</small>-galactopyranoside <ref name="chebi9630">{{cite web|url=http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9630|title=tomatine (CHEBI:9630)|author=EBI Web Team}}</ref> |
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| OtherNames = Tomatine, Tomatin, Lycopersicin |
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| OtherNames = Tomatine, Tomatin, Lycopersicin |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| CASNo_Ref = {{cascite|correct|??}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo = <!-- blanked - oldvalue: 17406-45-0 --> |
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| CASNo = 17406-45-0 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| PubChem = 623058 |
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| UNII = 31U6547O08 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| PubChem = 28523 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 525778 |
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| ChEMBL = 525778 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 26536 |
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| ChemSpiderID = 26536 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 9630 |
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| ChEBI = 9630 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C50H83NO21/c1-20-7-12-50(51-15-20)21(2)32-28(72-50)14-26-24-6-5-22-13-23(8-10-48(22,3)25(24)9-11-49(26,32)4)65-45-40(63)37(60)41(31(18-54)68-45)69-47-43(71-46-39(62)36(59)34(57)29(16-52)66-46)42(35(58)30(17-53)67-47)70-44-38(61)33(56)27(55)19-64-44/h20-47,51-63H,5-19H2,1-4H3/t20-,21-,22-,23-,24+,25-,26-,27+,28-,29+,30+,31+,32-,33-,34+,35+,36-,37+,38+,39+,40+,41-,42-,43+,44-,45+,46-,47-,48-,49-,50-/m0/s1 |
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| StdInChI =1S/C50H83NO21/c1-20-7-12-50(51-15-20)21(2)32-28(72-50)14-26-24-6-5-22-13-23(8-10-48(22,3)25(24)9-11-49(26,32)4)65-45-40(63)37(60)41(31(18-54)68-45)69-47-43(71-46-39(62)36(59)34(57)29(16-52)66-46)42(35(58)30(17-53)67-47)70-44-38(61)33(56)27(55)19-64-44/h20-47,51-63H,5-19H2,1-4H3/t20-,21-,22-,23-,24+,25-,26-,27+,28-,29+,30+,31+,32-,33-,34+,35+,36-,37+,38+,39+,40+,41-,42-,43+,44-,45+,46-,47-,48-,49-,50-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = REJLGAUYTKNVJM-SGXCCWNXSA-N |
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| StdInChIKey = REJLGAUYTKNVJM-SGXCCWNXSA-N |
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| SMILES = 12CC3()()(CC4(C)3()C3()O5(CC(C)CN5)(C)43)1(C)CC(C2)O1O(CO)(O2O(CO)(O)(O3OC(O)(O)3O)2O2O(CO)(O)(O)2O)(O)1O}} |
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| SMILES = C1CC2((3(O2)C43(CC54CC65(CC(C6)O7((((O7)CO)O8((((O8)CO)O)O9(((CO9)O)O)O)O2((((O2)CO)O)O)O)O)O)C)C)C)NC1 |
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}} |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula = C<sub>50</sub>H<sub>83</sub>NO<sub>21</sub> |
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| Formula = C<sub>50</sub>H<sub>83</sub>NO<sub>21</sub> <ref>1.http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+17406-45-0</ref> |
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| MolarMass = 1034.18816 |
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| MolarMass = 1034.18816 <ref>US Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safety Health. Registry of Toxic Effects of Chemical Substances (RTECS). National Library of Medicine's current MEDLARS file., p. 83/8212</ref> |
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| Appearance = crystalline solid |
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| Appearance = crystalline solid |
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| Density = |
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| Density = |
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| MeltingPt = 263-268 °C <ref name="auto1">The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 1228</ref> |
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| MeltingPt = |
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| Solubility = insoluble but soluble in methanol, ethanol, dioxane and propylene glycol<ref name="auto1"/> }} |
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| Section3 = {{Chembox Hazards |
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| Autoignition = }} |
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'''Tomatine''' (sometimes called '''tomatin''' or '''lycopersicin''') is a ], found in the stems and leaves of ] plants, and in the fruits at much lower concentrations. Chemically pure tomatine is a white crystalline solid at standard temperature and pressure.<ref name="chebi9630"/><ref>{{cite journal |doi=10.1093/nar/gkm791|pmid=17932057|pmc=2238832|title=ChEBI: A database and ontology for chemical entities of biological interest|journal=Nucleic Acids Research|volume=36|issue=Database issue|pages=D344–50|year=2007|last1=Degtyarenko|first1=K.|last2=De Matos|first2=P.|last3=Ennis|first3=M.|last4=Hastings|first4=J.|last5=Zbinden|first5=M.|last6=McNaught|first6=A.|last7=Alcantara|first7=R.|last8=Darsow|first8=M.|last9=Guedj|first9=M.|last10=Ashburner|first10=M.}}</ref> |
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Tomatine is sometimes confused with the glycoalkaloid ].<ref name="McGee" /> |
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== History == |
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Tomatoes were brought to Europe in the early 1500s. The English botanist ] was one of the first cultivators of the tomato plant. In his publication '']'', he considered tomatoes poisonous due to their levels of what would later be called tomatine, plus high acid content. Consequently, tomatoes were generally not eaten in Britain until the mid-18th century.<ref>{{cite web|url=http://smartkitchen.com/resources/tomato-s-culinary-history|title=Tomatoes Culinary History – Resource – Smart Kitchen – Online Cooking School|access-date=2016-03-10|archive-date=2017-08-06|archive-url=https://web.archive.org/web/20170806140530/https://smartkitchen.com/resources/tomato-s-culinary-history|url-status=dead}}</ref>{{Better source needed|date=November 2023}} |
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In 1837, the first medicinal tomato pills were advertised in the United States because of their positive effects upon the ] organs. The product “Phelp’s Compound Tomato Pills” was extracted from the tomato plant, and contained tomatine. The pills were made by the medic Guy R. Phelps, who stated that the alkaloid tomatine was one of the most useful discoveries ever made. Tomatine then was said to be an antidote to ].<ref>Andrew F. Smith; The tomato in America: Early History, Culture, and Cookery; University of South Carolina Press, 1994; 112. </ref> |
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In the mid 20th century, scientists from the ] were the first to isolate tomatine from the wild tomato species '']'' and the cultured species ''Lycopersicon esculentum''.<ref>Fontaine, T. D.; Irving, G. W., Jr.; Ma, R.; Poole, J. B.; Doolittle, S. P; Isolation and partial characterization of crystalline tomatine, an antibiotic agent from the tomato plant; Arch. Biochem. 1948; 18, 467-475.</ref><ref>Fontaine, T. D., Ard, J. S., Ma, R. M.; Tomatidine, a steroid secondary amine; J. Am. Chem. SOC, 1951; 73, 878-879.</ref> |
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== Structure and biosynthesis == |
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{{visible anchor|Alpha-tomatine}} ({{visible anchor|α-tomatine}}) belongs to the compound group steroidal ]. These compounds consist of an ], which is a ] derivative, and a carbohydrate chain, which in the case of α-tomatine consists of two ] units, a ] unit, and a ] unit.<ref name=":0">{{cite journal|doi=10.1016/j.phytochem.2014.12.010|pmid=25556315|title=The bitter side of the nightshades: Genomics drives discovery in Solanaceae steroidal alkaloid metabolism |journal=Phytochemistry |volume=113 |pages=24–32 |year=2015 |last1=Cárdenas |first1=P.D.|last2=Sonawane|first2=P.D.|last3=Heinig|first3=U.|last4=Bocobza|first4=S.E.|last5=Burdman|first5=S.|last6=Aharoni|first6=A.|bibcode=2015PChem.113...24C }}</ref> In α-tomatine, the tetrasaccharide called lycotetraose is attached to the O-3 of the steroidal aglycone.<ref>{{Cite journal|doi=10.1039/B508752J|pmid=16106302|title=Efficient synthesis of methyl lycotetraoside, the tetrasaccharide constituent of the tomato defence glycoalkaloid α-tomatine|journal=Organic & Biomolecular Chemistry|volume=3|issue=17|pages=3201–6|year=2005|last1=Jones|first1=Nigel A.|last2=Nepogodiev|first2=Sergey A.|last3=Field|first3=Robert A.}}</ref> At first it was thought that the synthesis of steroidal alkaloids only involved multiple steps of hydroxylation, oxidation and amination of cholesterol with ] as the source of the incorporated nitrogen. Later the glycoalkaloid metabolism genes were discovered.<ref name=":0" /> These genes produce the glycoalkaloid metabolism ]s, which are responsible for the synthesis of steroidal alkaloid aglycones in potato and tomato plants.<ref name=":0" /> The reaction these enzymes perform are shown in the figure 1. |
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== Mechanism of action == |
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Tomatine may play a major role in resistance of the tomato plant against fungal, microbial, insect, and herbivoral attack.{{citation needed|date=October 2016}} |
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The effects of the glycoalkaloids (to which tomatine belongs), can be divided in two main parts: the disruption of cellular membranes and the inhibition of the enzyme ]. Tomatine is responsible in tomato plants for resistance against for example the ] and to ]s.<ref name=":1">Milner, Sinead Eileen, et al. "Bioactivities of glycoalkaloids and their aglycones from Solanum species." Journal of agricultural and food chemistry 59.8 (2011): 3454-3484.</ref> It is also a defense against fungi.<ref name="Friedman">Friedman, Mendel; Tomato glycoalkaloids: role in the plant and in the diet; Journal of Agricultural and Food Chemistry 50.21, 2002; 5751-5780.</ref><ref name=":3">Hoagland, Robert E.; Toxicity of tomatine and tomatidine on weeds, crops and phytopathogenetic fungi.; Allelopathy J 23.2, 2009; 425-436.</ref> |
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=== Membrane disruption === |
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The membrane disruptive properties of tomatine are caused by the ability to form 1:1 complexes with ]. A possible mechanism of the membrane disruption by glycoalkaloids is displayed in figure 2. First, the ] part of tomatine binds reversibly to ] in the membrane (figure 2, part 2). When this reaches a certain density, the glycosidic residues of the glycoalkaloids interact with each other by electrostatic interactions. This interaction catalyzes the development of an irreversible matrix of glycoalkaloid-sterol complexes (figure 2, part 4). In this way, the ] from the external membrane are immobilized and membrane budding will arise. Tubular structures are formed, because of the structure of tomatine (figure 2, part 6).<ref name=":1" /><ref name=":4">Keukens, Erik AJ, et al; Dual specificity of sterol-mediated glycoalkaloid induced membrane disruption; Biochimica et Biophysica Acta (BBA) - Biomembranes 1110.2, 1992; 127-136.</ref> |
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This membrane disruption causes cell death by cell leakage.<ref name=":1" /> Also, the disrupted membrane has an influence on sodium transport, by altering the membrane potential and reducing active sodium transport. When tomatine is orally ingested, the brush border of the intestine is damaged by the membrane-disruptive properties of tomatine, so increased uptake of macromolecules occurs. This damage to the epithelial barriers is dose-dependent.<ref name=":1" /><ref name=":4" /> |
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Tomatine is considered to be a fungitoxic compound, as it completely inhibits ] growth of the fungi ''C. orbiculare'' (MC100=2.0 mM), ''S. linicola'' (MC100=0.4 mM), and ''H. turcicum'' (MC100=0.13 mM). For the inhibition at a low ], much more tomatine is required, so the compound is more effectively fungitoxic at a high pH, when the alkaloid is ]. The unprotonated form of tomatine forms complexes with ] such as cholesterol, which may cause disruption of cell membrane and changes in membrane permeability.<ref>Arneson, P.A., Durbin, R.D.; Studies on the Mode of Action of Tomatine as a Fungitoxic Agent.; USDA Pioneering Research Laboratory, 1967.</ref> |
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Tomatine is effective against ] at pH 8 but not at pH 4. A possible explanation for this is that the tomatine only in the deprotonated form binds to ] to form the earlier mentioned complexes.<ref name="Friedman" /> Tomatine disrupts ] membranes containing 3-β-hydroxy sterol, while ] without 3-β-hydroxy sterols are resistant to membrane disruption.<ref name=":3" /> Tomatine inhibits also the fungal types ''Ph. infestans'' and ''Py. aphanidermatum'', which do not have any ] in their membranes, so another mechanism of action must be present.<ref name="Friedman" /> |
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=== Inhibition of acetylcholinesterase === |
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The other known action of the compound is the pH-dependent competitive inhibition of the enzyme ].<ref name=":1" /><ref name="Friedman" /> The majority of synthetic pesticides used in agriculture work by inhibition of acetylcholinesterase to kill insects.<ref>Bushway, Rodney J., Sharon A. Savage, and Bruce S. Ferguson; Inhibition of acetyl cholinesterase by solanaceous glycoalkaloids and alkaloids; American Potato Journal 64.8, 1987; </ref> |
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== Metabolism == |
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Even now, little is known about the bioavailability, pharmacokinetics and metabolism of the ] in humans.<ref name=":1" /> One important factor is the poor uptake of tomatine into general blood circulation. When tomatine is orally ingested, much tomatine may form complexes with ] from the other food present in the stomach. The complexes of tomatine and cholesterol are not absorbed in the intestine, but are excreted.<ref name="Friedman" /> For the complexation with cholesterol to occur, the presence of a ] chain is essential. The ] ], which is tomatine without the sugars, does not form the complexes.<ref name=":1" /><ref name=":4" /> The complexation probably occurs in the ], because the acidic conditions in the stomach itself lead to ] of the tomatine, and the protonated form of tomatine does not bind to cholesterol.<ref name="Friedman" /> |
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Hydrolysis of tomatine likely takes place, but whether it is acid- or ]-catalyzed is not known.<ref name="Friedman" /> The ] of tomatine likely leads to the formation of tomatidine, which is the aglycon of tomatine. Tomatidine is a metabolite which may not be completely nontoxic; it could have effects on the human body.<ref name="Friedman" /> |
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Fungal ] enzymes can transform tomatine to deactivate it. Detoxification can take place by removing one glucose residue. Other fungal species hydrolyze tomatine to the less toxic aglycon tomatidine by removing all the sugar residues. Tomatidine can still inhibit some fungal species, but is less toxic than tomatine. Fungi use diverse pathways for the hydrolysis of tomatine. Also, the level of toxicity depends on the type of fungus.<ref name=":3" /><ref>Arneson, P. A., and R. D. Durbin.; Studies on the mode of action of tomatine as a fungitoxic agent.; Plant physiology 43.5, 1968; 683-686.</ref> The metabolite tomatidine can be hydrolyzed further by membrane-bound CYP-450 oxygenases.<ref name="Friedman" /> |
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== Uses == |
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Tomatine has been used as a ] in ] for precipitating ] from solution.<ref>{{ cite journal | last1= Cayen |first1=M. N. | title = Effect of dietary tomatine on cholesterol metabolism in the rat | journal = Journal of Lipid Research | volume = 12 | issue = 4 | pages = 482–90 | year = 1971 |doi=10.1016/S0022-2275(20)39498-0 | pmid = 4362143 | url = http://www.jlr.org/cgi/pmidlookup?view=long&pmid=4362143 | doi-access = free }}</ref> Also, tomatine is known to be an ] in connection with certain ] ]s.<ref>{{ cite journal |last1=Heal |first1=K. G. |last2=Taylor-Robinson |first2=A. W. | title = Tomatine Adjuvantation of Protective Immunity to a Major Pre-erythrocytic Vaccine Candidate of Malaria is Mediated via CD8<sup>+</sup> T Cell Release of IFN-γ | journal = Journal of Biomedicine and Biotechnology | year = 2010 | volume = 2010 | page = 834326 | pmid = 20300588 | pmc = 2837906 | doi = 10.1155/2010/834326|doi-access=free }}</ref> |
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== Toxicity == |
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The possible risks of tomatine for humans have not been formally studied, so no ] can be deduced. The toxicity of tomatine has only been studied on laboratory animals. The symptoms of acute tomatine poisoning in animals are similar to the symptoms of poisoning by ], a potato ]. These symptoms include vomiting, diarrhea, abdominal pain, drowsiness, confusion, weakness, and depression.<ref>Morris, S.C., Lee, T.H; The toxicity and teratogenicity of Solanaceae glycoalkaloids, particularly those of the potato (Solanum tuberosum): a review.; Food Techn. Aust., 1984; 118-124.</ref> Generally, tomatine is regarded to cause less toxic effects to mammals than other alkaloids such as solanine.<ref>{{Cite journal|pmc=45543|year=1994|last1=Rick|first1=C. M.|title=High alpha-tomatine content in ripe fruit of Andean Lycopersicon esculentum var. Cerasiforme: Developmental and genetic aspects|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=91|issue=26|pages=12877–12881|last2=Uhlig|first2=J. W.|last3=Jones|first3=A. D.|pmid=7809139|doi=10.1073/pnas.91.26.12877|bibcode=1994PNAS...9112877R|doi-access=free}}</ref> |
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The human consumption of moderate amounts of tomatine seems to occur without notable toxic effects. This is reinforced by the widespread consumption of “pickled green” and “]” and the consumption of high-tomatine tomatoes (a variant of ''L. esculentum'' var. cerasiforme, better known as the "]", indigenous to Peru) with very high tomatine content (in the range of 500–5000 μg/kg of ]).<ref>Rick, C. M., Uhlig, J. W., Jones, A. D.; High R-tomatine content in ripe fruit of Andean Lycopersicon esculentum Var. cerasiforme: developmental and genetic aspects.; Proc. Natl. Acad. Sci., 1994; 91, 12877-12881.</ref> |
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''New York Times'' food science writer ] found scant evidence for tomato toxicity in the medical and veterinary literature, and observed that dried tomato leaves (which contain higher concentrations of alkaloids than the fruits) are occasionally used as a food ] or garnish, without problems. He also reported that an adult human would probably have to eat over half a kilogram of tomato leaves to ingest a toxic (not necessarily lethal) dose.<ref name="McGee ">{{cite news| url=https://www.nytimes.com/2009/07/29/dining/29curi.html | work=The New York Times | title=Accused, Yes, but Probably Not a Killer | first=Harold | last=McGee | date=July 29, 2009 | access-date=2016-11-03}}</ref> |
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== See also == |
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* ] |
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* ] |
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==References== |
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{{Reflist|30em}} |
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==External links== |
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*{{Commons category-inline}} |
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