View source for Trehalose

{{Distinguish|Trehalulose}}
{{Chembox
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| verifiedrevid  = 477174498
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| ImageFile      = Trehalose.svg
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| ImageClass     = skin-invert-image
| ImageFile1     = Trehalose-from-xtal-2008-CM-3D-balls.png
| ImageClass1    = bg-transparent
| ImageFile2     = Trehalose-from-xtal-2008-CM-3D-SF.png
| ImageClass2    = bg-transparent
| OtherNames     = α,α‐Trehalose, mycose, tremalose
| IUPACName      = α-<small>D</small>-Glucopyranosyl α-<small>D</small>-glucopyranoside
| SystematicName = (2''R'',3''S'',4''S'',5''R'',6''R'')-2-(Hydroxymethyl)-6-[(2''R'',3''R'',4''S'',5''S'',6''R'')-3,4,
5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol
| Section1       = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 7149
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1236395
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = B8WCK70T7I
| InChI = 1/C12H22O11/c13-1-3-5(15)7(17)9(19)11(21-3)23-12-10(20)8(18)6(16)4(2-14)22-12/h3-20H,1-2H2/t3-,4-,5-,6-,7+,8+,9-,10-,11-,12-/m1/s1
| InChIKey = HDTRYLNUVZCQOY-LIZSDCNHBN
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16551
| SMILES = OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O1)O[C@@H]2[C@H](O)[C@@H](O)[C@H](O)[C@H](O2)CO
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| StdInChI = 1S/C12H22O11/c13-1-3-5(15)7(17)9(19)11(21-3)23-12-10(20)8(18)6(16)4(2-14)22-12/h3-20H,1-2H2/t3-,4-,5-,6-,7+,8+,9-,10-,11-,12-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HDTRYLNUVZCQOY-LIZSDCNHSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 99-20-7
| CASNo_Comment = (anhydrous)
| CASNo1_Ref = {{cascite|changed|??}}
| CASNo1 = 6138-23-4
| CASNo1_Comment = (dihydrate)
| PubChem = 7427
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| Section2       = {{Chembox Properties
| Formula = C<sub>12</sub>H<sub>22</sub>O<sub>11</sub> (anhydride)
| MolarMass = 342.296 g/mol (anhydrous)<br />378.33 g/mol (dihydrate)
| Appearance = White [[orthorhombic]] crystals
| Density = 1.58 g/cm<sup>3</sup> at 24 °C
| MeltingPtC = 203
| MeltingPt_notes = (anhydrous)<br />97 °C (dihydrate)
| BoilingPt =
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| Solubility = 68.9&nbsp;g per 100&nbsp;g at 20&nbsp;°C<ref>{{Cite journal|url=http://www.iupac.org/publications/pac/2002/pdf/7407x1263.pdf |journal= Pure Appl. Chem. |volume=74|issue=7|pages=1263–1269|year=2002|doi=10.1351/pac200274071263|title=Novel functions and applications of trehalose|last1=Higashiyama|first1=Takanobu |s2cid= 28311022 }}</ref>
| SolubleOther = Slightly soluble in [[ethanol]], insoluble in [[diethyl ether]] and [[benzene]]<ref name="hand">{{Cite book | last = Lide | first = David R. | year = 1998 | title = Handbook of Chemistry and Physics | edition = 87 | location = Boca Raton, Florida | publisher = CRC Press | isbn = 978-0-8493-0594-8 | pages = 3–534 }}</ref>
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| Section6       = {{Chembox Explosive
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| Section7       = {{Chembox Hazards
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| Section8       = {{Chembox Related
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}}

'''Trehalose''' is a [[Carbohydrate|sugar]] derived from two molecules of [[glucose]].  Trehalose is a [[disaccharide]] formed by a {{nobr|1,1-[[glycosidic]]}} bond between two α-[[glucose]] units. It is found in nature as a disaccharide and also as a monomer in some polymers.<ref name=Elbein2003/> Two other [[stereoisomer]]s exist: α,β-trehalose, also called ''neotrehalose'', and β,β-trehalose, also called ''isotrehalose''. Neither of these alternate isomers has been isolated from living organisms, but isotrehalose has been found in starch hydroisolates.<ref name=Elbein2003/> Some bacteria, fungi, plants and invertebrate animals synthesize it as a source of energy, and to survive freezing and lack of water.

==Synthesis==
At least three biological pathways support trehalose [[biosynthesis]].<ref name=Elbein2003>{{cite journal |last1=Elbein |first1=Alan D. |last2=Pan |first2=Y. T. |last3=Pastuszak |first3=Irena |last4=Carroll |first4=David |title=New insights on trehalose: a multifunctional molecule |journal=Glycobiology |date=April 2003 |volume=13 |issue=4 |pages=17R–27R |doi=10.1093/glycob/cwg047 |pmid=12626396 |issn=0959-6658 | doi-access = free }}</ref> An industrial process can derive trehalose from [[corn starch]].<ref>{{Cite report |url=https://www.fda.gov/downloads/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm261213.pdf |archive-url=https://wayback.archive-it.org/7993/20171031055001/https://www.fda.gov/downloads/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm261213.pdf |archive-date=2017-10-31 |title = GRAS Notification for Hayashibara Trehalose |date = May 3, 2000 | page = 10 |publisher= Food and Drug Administration}}</ref>

== Properties ==

=== Chemical ===
Trehalose is a [[Reducing sugar|nonreducing sugar]] formed from two glucose units joined by a 1–1 alpha bond, giving it the name {{em|{{nobr|α-{{small|D}}-gluco}}{{shy}}{{nobr|pyranosyl-(1→1)-α-{{small|D}}-gluco}}{{shy}}pyranoside}}. The bonding makes trehalose very resistant to acid [[hydrolysis]], and therefore is stable in solution at high temperatures, even under acidic conditions. The bonding keeps nonreducing sugars in closed-ring form, such that the [[aldehyde]] or [[ketone]] end groups do not bind to the [[lysine]] or [[arginine]] residues of proteins (a process called [[glycation]]).  Trehalose is less soluble than [[sucrose]], except at high temperatures (>80&nbsp;°C). Trehalose forms a rhomboid crystal as the dihydrate, and has 90% of the calorific content of sucrose in that form. Anhydrous forms of trehalose readily regain moisture to form the [[Hydrate|dihydrate]]. [[Anhydrous]] forms of trehalose can show interesting physical properties when heat-treated.{{clarification needed|date=February 2025}}

Trehalose aqueous solutions show a concentration-dependent clustering tendency. Owing to their ability to form [[hydrogen bond]]s, they self-associate in water to form clusters of various sizes. All-atom molecular dynamics simulations showed that concentrations of 1.5–2.2 molar allow trehalose molecular clusters to [[percolation|percolate]]{{clarification needed|date=May 2025}} and form large and continuous aggregates.<ref>{{cite journal |last1=Sapir |first1=Liel |last2=Harries |first2=Daniel |title=Linking Trehalose Self-Association with Binary Aqueous Solution Equation of State |journal=The Journal of Physical Chemistry B |date=3 February 2011 |volume=115 |issue=4 |pages=624–634 |doi=10.1021/jp109780n | pmid = 21186829 }}</ref>

Trehalose directly interacts with nucleic acids, facilitates melting of double stranded DNA and stabilizes single-stranded nucleic acids.<ref>{{cite journal |last1=Bezrukavnikov |first1=Sergey |last2=Mashaghi |first2=Alireza |last3=van Wijk |first3=Roeland J. |last4=Gu |first4=Chan |last5=Yang |first5=Li Jiang |last6=Gao |first6=Yi Qin |last7=Tans |first7=Sander J. |title=Trehalose facilitates DNA melting: a single-molecule optical tweezers study |journal=Soft Matter |date=6 August 2014 |volume=10 |issue=37 |pages=7269–7277 |doi=10.1039/C4SM01532K | pmid = 25096217 | bibcode = 2014SMat...10.7269B }}</ref>

=== Biological  ===
Organisms ranging from bacteria, yeast, fungi, insects, invertebrates, and lower and higher plants have enzymes that can make trehalose.<ref name=Elbein2003/>
In nature, trehalose can be found in [[plants]], and [[microorganisms]].  In animals, trehalose is prevalent in shrimp, and also in [[insects]], including grasshoppers, locusts, butterflies, and bees, in which trehalose serves as blood-sugar.<ref>{{cite journal |last1=Richards |first1=A.B |last2=Krakowka |first2=S |last3=Dexter |first3=L.B |last4=Schmid |first4=H |last5=Wolterbeek |first5=A.P.M |last6=Waalkens-Berendsen |first6=D.H |last7=Shigoyuki |first7=A |last8=Kurimoto |first8=M |title=Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies |journal=Food and Chemical Toxicology |date=July 2002 |volume=40 |issue=7 |pages=871–898 |doi=10.1016/S0278-6915(02)00011-X|pmid=12065209 }}</ref><ref>{{cite journal |last1=Shukla |first1=E. |last2=Thorat |first2=L. J. |last3=Nath |first3=B. B. |last4=Gaikwad |first4=S. M. |title=Insect trehalase: Physiological significance and potential applications |journal=Glycobiology |date=1 April 2015 |volume=25 |issue=4 |pages=357–367 |doi=10.1093/glycob/cwu125|pmid=25429048 }}</ref> [[Trehalase]] [[gene]]s are found in [[tardigrade]]s, the microscopic [[ecdysozoan]]s found worldwide in diverse extreme environments.<ref name="kamilari">{{cite journal | last1=Kamilari | first1=Maria | last2=Jørgensen | first2=Aslak | last3=Schiøtt | first3=Morten | last4=Møbjerg | first4=Nadja | title=Comparative transcriptomics suggest unique molecular adaptations within tardigrade lineages | journal=BMC Genomics | volume=20 | issue=1 | date=2019-07-24 | page=607 | issn=1471-2164 | pmid=31340759 | pmc=6652013 | doi=10.1186/s12864-019-5912-x | doi-access=free }}</ref>

Trehalose is the major carbohydrate energy storage molecule used by insects for flight.<ref name="Shukla_et_al_2015">{{cite journal |last1=Shukla |first1=E |last2=Thorat |first2=LJ |last3=Nath |first3=BB |last4=Gaikwad |first4=SM |title=Insect trehalase: physiological significance and potential applications. |journal=Glycobiology |date=April 2015 |volume=25 |issue=4 |pages=357–67 |doi=10.1093/glycob/cwu125 |pmid=25429048}}</ref> One possible reason for this is that the [[Glycosidic bond|glycosidic linkage]] of trehalose, when acted upon by an insect trehalase, releases two molecules of glucose, which is required for the rapid energy requirements of flight. This is double the efficiency of glucose release from the storage polymer [[starch]], for which cleavage of one glycosidic linkage releases only one glucose molecule.{{citation needed|date=March 2018}}

The concentrations of both trehalose and glucose in the insect [[hemolymph]] are tightly controlled by multiple enzymes and hormones, including [[trehalase]], [[insulin]]-like peptides (ILPs and DILPs), [[adipokinetic hormone]] (AKH), leucokinin (LK), [[octopamine]] and other mediators, thereby maintaining carbohydrate [[homeostasis]] by endocrine and metabolic [[feedback]] mechanisms.<ref name="Becker_et_al_1996">{{cite journal |last1=Becker |first1=A |last2=Schlöder |first2=P |last3=Steele |first3=JE |last4=Wegener |first4=G |title=The regulation of trehalose metabolism in insects |journal=Experientia |date=15 May 1996 |volume=52 |issue=5 |pages=433–9 |doi=10.1007/BF01919312 |pmid=8706810}}</ref><ref name="Tellis_et_al_2023">{{cite journal |last1=Tellis |first1=MB |last2=Kotkar |first2=HM |last3=Joshi |first3=RS |title=Regulation of trehalose metabolism in insects: from genes to the metabolite window. |journal=Glycobiology |date=17 May 2023 |volume=33 |issue=4 |pages=262–273 |doi=10.1093/glycob/cwad011 |pmid=36762907}}</ref><ref name="Naessel_and_Vandenbroek">{{cite journal |last1=Nässel |first1=DR |last2=Vanden Broeck |first2=J |title=Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides. |journal=Cellular and Molecular Life Sciences  |date=January 2016 |volume=73 |issue=2 |pages=271–90 |doi=10.1007/s00018-015-2063-3 |pmid=26472340|pmc=11108470 }}</ref><ref name="Naessel_and_Zandawala_2022">{{cite journal |last1=Nässel |first1=DR |last2=Zandawala |first2=M |title=Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions. |journal=Open Biology |date=July 2022 |volume=12 |issue=7 |article-number=220174 |doi=10.1098/rsob.220174 |pmid=35892199|pmc=9326288 }}</ref>

In plants, trehalose is present in sunflower seeds, [[moonwort]], ''[[Selaginella]]'' plants,<ref name="Plant Physiology">{{cite journal |last1=Zentella |first1=Rodolfo |last2=Mascorro-Gallardo |first2=José O. |last3=Van Dijck |first3=Patrick |last4=Folch-Mallol |first4=Jorge |last5=Bonini |first5=Beatriz |last6=Van Vaeck |first6=Christophe |last7=Gaxiola |first7=Roberto |last8=Covarrubias |first8=Alejandra A. |last9=Nieto-Sotelo |first9=Jorge |last10=Thevelein |first10=Johan M. |last11=Iturriaga |first11=Gabriel |title=A ''Selaginella lepidophylla'' Trehalose-6-Phosphate Synthase Complements Growth and Stress-Tolerance Defects in a Yeast tps1 Mutant1 |journal=Plant Physiology |date=1 April 1999 |volume=119 |issue=4 |pages=1473–1482 |doi=10.1104/pp.119.4.1473 | pmid = 10198107 | pmc = 32033}}</ref> and sea algae. Within the fungi, it is prevalent in some mushrooms, such as [[shiitake]] (''Lentinula edodes''), [[Pleurotus ostreatus|oyster]], [[King oyster mushroom|king oyster]], and [[Golden needle mushroom|golden needle]].<ref>{{cite journal |last1=Reis |first1=Filipa S. |last2=Barros |first2=Lillian |last3=Martins |first3=Anabela |last4=Ferreira |first4=Isabel C.F.R. |title=Chemical composition and nutritional value of the most widely appreciated cultivated mushrooms: An inter-species comparative study |journal=Food and Chemical Toxicology |date=February 2012 |volume=50 |issue=2 |pages=191–197 |doi=10.1016/j.fct.2011.10.056 | pmid = 22056333 | hdl = 10198/7341 | s2cid = 23997767 | url = https://bibliotecadigital.ipb.pt/bitstream/10198/7341/5/Reis_et_al_FCT_revised_2.pdf | hdl-access = free }}</ref>

Even within the plant kingdom, ''[[Spike moss|Selaginella]]'' (sometimes called the resurrection plant), which grows in desert and mountainous areas, may be cracked and dried out, but will turn green again and revive after rain because of the function of trehalose.<ref name="Plant Physiology" />

The two prevalent theories as to how trehalose works within the organism in the state of [[cryptobiosis]] are the [[Cryopreservation#Vitrification|vitrification]] theory, a state that prevents ice formation, or the water displacement theory, whereby water is replaced by trehalose.<ref name=kamilari/><ref>{{cite journal |last1=Sola-Penna |first1=Mauro |last2=Meyer-Fernandes |first2=José Roberto |title=Stabilization against Thermal Inactivation Promoted by Sugars on Enzyme Structure and Function: Why Is Trehalose More Effective Than Other Sugars? |journal=Archives of Biochemistry and Biophysics |date=December 1998 |volume=360 |issue=1 |pages=10–14 |doi=10.1006/abbi.1998.0906 | pmid = 9826423}}</ref>

In bacterial cell wall, trehalose has a structural role in adaptive responses to stress such as osmotic differences and extreme temperature.<ref>{{Cite journal|last1=Iturriaga|first1=Gabriel|last2=Suárez|first2=Ramón|last3=Nova-Franco|first3=Barbara|date=2009|title=Trehalose Metabolism: From Osmoprotection to Signaling|journal=International Journal of Molecular Sciences|language=en|volume=10|issue=9|pages=3793–3810|doi=10.3390/ijms10093793|pmid=19865519|pmc=2769160|doi-access=free}}</ref> Yeast uses trehalose as a carbon source in response to abiotic stresses.<ref name="Pucker-2016" /> In humans, trehalose is thought to act as a neuroprotective by inducing [[autophagy]] and thereby clearing [[Protein aggregation|protein aggregates]].<ref>{{cite journal |last1=Lee |first1=He-Jin |last2=Yoon |first2=Ye-Seul |last3=Lee |first3=Seung-Jae |title=Mechanism of neuroprotection by trehalose: controversy surrounding autophagy induction |journal=Cell Death & Disease |date=15 June 2018 |volume=9 |issue=7 |page=712 |doi=10.1038/s41419-018-0749-9|pmid=29907758 |pmc=6003909 }}</ref><ref>{{cite journal |last1=Sevriev |first1=Borislav |last2=Dimitrova |first2=Simeonka |last3=Kehayova |first3=Gabriela |last4=Dragomanova |first4=Stela |title=Trehalose: Neuroprotective Effects and Mechanisms—An Updated Review |journal=NeuroSci |date=12 October 2024 |volume=5 |issue=4 |pages=429–444 |doi=10.3390/neurosci5040032|doi-access=free |pmid=39484301 |pmc=11503274 }}</ref>

Trehalose has also been reported for anti-bacterial, anti-biofilm, and anti-inflammatory (''in vitro'' and ''in vivo'') activities, upon its esterification with fatty acids of varying chain lengths.<ref>{{Cite journal|last1=Marathe|first1=Sandesh J.|last2=Shah|first2=Nirali N.|last3=Singhal|first3=Rekha S.|date=2020-01-01|title=Enzymatic synthesis of fatty acid esters of trehalose: Process optimization, characterization of the esters and evaluation of their bioactivities|url=https://www.sciencedirect.com/science/article/pii/S0045206819311368|journal=Bioorganic Chemistry|language=en|volume=94|article-number=103460|doi=10.1016/j.bioorg.2019.103460|pmid=31791682|s2cid=208610507|issn=0045-2068|url-access=subscription}}</ref>

== Nutritional and dietary properties ==
Trehalose is rapidly broken down into glucose by the [[enzyme]] [[trehalase]], which is present in the [[brush border]] of the [[intestinal mucosa]] of omnivores (including humans) and herbivores.<ref>{{cite book|editor1-last=Mathlouthi|editor1-first=M.|title=Food packaging and preservation |date=1999|publisher=Aspen Publishers|location=Gaithersburg, Md.|isbn=978-0-8342-1349-4 |url=https://books.google.com/books?id=gNkTBKZrcloC&q=trehalose+dietary+brush+border&pg=PA135|access-date=25 June 2014}}</ref>{{Rp|135}} It causes less of a spike in [[blood sugar]] than glucose.<ref name=Collins/>  Trehalose has about 45% the sweetness of sucrose at concentrations above 22%, but when the concentration is reduced, its sweetness decreases more quickly than that of sucrose, so that a 2.3% solution tastes 6.5 times less sweet as the equivalent sugar solution.<ref>{{cite book|editor1-last=O'Brien-Nabors|editor1-first=Lyn|title=Alternative sweeteners|date=2012|publisher=CRC Press|location=Boca Raton|isbn=978-1-4398-4614-8|edition=4th |url=https://books.google.com/books?id=coDPwzFX7rAC&pg=PA444|access-date=25 June 2014}}</ref>{{Rp|444}}

It is commonly used in prepared frozen foods, like ice cream, because it [[Freezing-point depression|lowers the freezing point]] of foods.<ref name=Collins/>

Deficiency of trehalase enzyme is unusual in humans, except in the [[Greenlandic Inuit]], where it is present in only 10–15% of the population.<ref>{{cite book|last1=Kohlmeier|first1=Martin |title=Nutrient Metabolism |date=2003 |publisher=Elsevier|location=Burlington|isbn=978-0-08-053789-4|url=https://books.google.com/books?id=sAwqrHtcyM8C&q=trehalose+dietary&pg=PA197|access-date=25 June 2014}}</ref>{{Rp|197}}

== Metabolism ==
Five biosynthesis pathways have been reported for trehalose. The most common pathway is TPS/TPP pathway which is used by organisms that synthesize trehalose using the enzyme trehalose-6-phosphate (T6P) synthase (TPS).<ref>{{Cite journal|last1=Cabib|first1=E.|last2=Leloir|first2=L. F.|year=1958|title=The biosynthesis of trehalose phosphate|journal=The Journal of Biological Chemistry|volume=231|issue=1|pages=259–275|doi=10.1016/S0021-9258(19)77303-7|issn=0021-9258|pmid=13538966|doi-access=free|hdl=11336/135983|hdl-access=free}}</ref> Second, trehalose synthase (TS) in certain types of bacteria could produce trehalose by using maltose and another disaccharide with two glucose units as substrates.<ref>{{Cite journal|last1=Nishimoto|first1=T.|last2=Nakano|first2=M.|last3=Nakada|first3=T.|last4=Chaen|first4=H.|last5=Fukuda|first5=S.|last6=Sugimoto|first6=T.|last7=Kurimoto|first7=M.|last8=Tsujisaka|first8=Y.|date=April 1996|title=Purification and properties of a novel enzyme, trehalose synthase, from Pimelobacter sp. R48|journal=Bioscience, Biotechnology, and Biochemistry|volume=60|issue=4|pages=640–644|doi=10.1271/bbb.60.640|issn=0916-8451|pmid=8829531|doi-access=free}}</ref> Third, the TreY-TreZ pathway in some bacteria converts starch that contain maltooligosaccharide or glycogen directly into trehalose.<ref>{{Cite journal|last1=Maruta|first1=Kazuhiko|last2=Mitsuzumi|first2=Hitoshi|last3=Nakada|first3=Tetsuya|last4=Kubota|first4=Michio|last5=Chaen|first5=Hiroto|last6=Fukuda|first6=Shigeharu|last7=Sugimoto|first7=Toshiyuki|last8=Kurimoto|first8=Masashi|date=1996-12-06|title=Cloning and sequencing of a cluster of genes encoding novel enzymes of trehalose biosynthesis from thermophilic archaebacterium Sulfolobus acidocaldarius|url=https://www.sciencedirect.com/science/article/pii/S0304416596000827|journal=Biochimica et Biophysica Acta (BBA) - General Subjects|language=en|volume=1291|issue=3|pages=177–181|doi=10.1016/S0304-4165(96)00082-7|pmid=8980629|issn=0304-4165|url-access=subscription}}</ref> Fourth, in primitive bacteria, trehalose glycisyltransferring synthase (TreT) produces trehalose from ADP-glucose and glucose.<ref>{{Cite journal|last1=Qu|first1=Qiuhao|last2=Lee|first2=Sung-Jae|last3=Boos|first3=Winfried|date=2004-11-12|title=TreT, a Novel Trehalose Glycosyltransferring Synthase of the Hyperthermophilic Archaeon Thermococcus litoralis*|journal=Journal of Biological Chemistry|language=English|volume=279|issue=46|pages=47890–47897|doi=10.1074/jbc.M404955200|issn=0021-9258|pmid=15364950|doi-access=free}}</ref> Fifth, trehalose phosphorylase (TreP) either hydrolyses trehalose into glucose-1-phosphate and glucose or may act reversibly in certain species.<ref>{{Cite journal|last1=Ren|first1=Yuanyuan|last2=Dai|first2=Xiuyu|last3=Zhou|first3=Jian|last4=Liu|first4=Jingfang|last5=Pei|first5=Huadong|last6=Xiang|first6=Hua|date=2005-05-01|title=Gene expression and molecular characterization of a thermostable trehalose phosphorylase fromThermoanaerobacter tengcongensis|journal=Science in China Series C: Life Sciences|language=en|volume=48|issue=3|pages=221–227|doi=10.1007/BF03183615|pmid=16092754|s2cid=23443429|issn=1862-2798}}</ref> Vertebrates do not have the ability to synthesize or store trehalose.<ref>{{Citation|last=Elbein|first=Alan D.|title=The Metabolism of α,α-Trehalose**The work cited from the author's laboratory was supported by grants from the Robert A. Welch Foundation and the National Institutes of Health (AI 09402).|date=1974-01-01|url=https://www.sciencedirect.com/science/article/pii/S0065231808602668|journal=Advances in Carbohydrate Chemistry and Biochemistry|volume=30|pages=227–256|editor-last=Tipson|editor-first=R. Stuart|publisher=Academic Press|doi=10.1016/S0065-2318(08)60266-8 |pmid=4377836 |language=en|access-date=2021-11-30|editor2-last=Horton|editor2-first=Derek|url-access=subscription}}</ref> Trehalase in humans is found only in specific location such as the intestinal mucosa, renal brush-border, liver and blood. Expression of this enzyme in vertebrates is initially found during the gestation period that is the highest after weaning. Then, the level of trehalase remained constant in the intestine throughout life.<ref>{{Cite journal|last=Galand|first=G.|date=1989|title=Brush border membrane sucrase-isomaltase, maltase-glucoamylase and trehalase in mammals. Comparative development, effects of glucocorticoids, molecular mechanisms, and phylogenetic implications|journal=Comparative Biochemistry and Physiology. B, Comparative Biochemistry|volume=94|issue=1|pages=1–11|doi=10.1016/0305-0491(89)90002-3|issn=0305-0491|pmid=2513162}}</ref> Meanwhile, diets consisting of plants and fungi contain trehalose. Moderate amount of trehalose in diet is essential and having low amount of trehalose could result in diarrhea, or other intestinal symptoms.<ref>{{Cite journal|last=Thevelein|first=J M|date=March 1984|title=Regulation of trehalose mobilization in fungi.|journal=Microbiological Reviews|volume=48|issue=1|pages=42–59|doi=10.1128/mr.48.1.42-59.1984|issn=0146-0749|pmid=6325857|pmc=373002}}</ref>

== Medical use ==
Trehalose is an ingredient, along with [[hyaluronic acid]], in an [[artificial tears]] product used to treat [[keratoconjunctivitis sicca|dry eye]].<ref>{{cite journal |last1=Stolz |first1=John |last2=Pinto-Bonilla |first2=Juan Carlos |last3=Del Olmo-Jimeno |first3=Alberto |last4=Llovet Osuna |first4=Fernando |last5=Hernandez Galilea |first5=Emiliano |title=A randomized crossover study comparing trehalose/hyaluronate eyedrops and standard treatment: patient satisfaction in the treatment of dry eye syndrome |journal=Therapeutics and Clinical Risk Management |date=April 2015 |volume=11 |pages=595–603 |doi=10.2147/TCRM.S77091 |pmid = 25926736 | pmc = 4403513 | doi-access = free }}</ref><ref name="Pucker-2016">{{cite journal |last1=Pucker |first1=Andrew D |last2=Ng |first2=Sueko M |last3=Nichols |first3=Jason J |title=Over the counter (OTC) artificial tear drops for dry eye syndrome |journal=Cochrane Database of Systematic Reviews |date=23 February 2016 |volume=2016 |issue=2 |article-number=CD009729 |doi=10.1002/14651858.CD009729.pub2 | pmid = 26905373 | pmc = 5045033}}</ref> Outbreaks of ''[[Clostridioides difficile (bacteria)|Clostridioides difficile]]'' were initially associated with trehalose,<ref name=Collins>{{cite journal |last1=Collins|first1=Francis |title=Has an Alternative to Table Sugar Contributed to the C. Diff. Epidemic?|url=https://directorsblog.nih.gov/2018/01/09/has-a-sucrose-alternative-contributed-to-the-c-diff-epidemic/|archive-url=https://web.archive.org/web/20180109153341/https://directorsblog.nih.gov/2018/01/09/has-a-sucrose-alternative-contributed-to-the-c-diff-epidemic/|archive-date=January 9, 2018|journal=NIH Director's Blog|date=9 January 2018}}</ref><ref name="pmid29345660">{{cite journal |last1=Ballard |first1=Jimmy D. |title=Pathogens boosted by food additive |journal=Nature |date=18 January 2018 |volume=553 |issue=7688 |pages=285–286 |doi=10.1038/d41586-017-08775-4| pmid = 29345660 | doi-access = free }}</ref><ref>{{cite journal |last1=Collins |first1=J. |last2=Robinson |first2=C. |last3=Danhof |first3=H. |last4=Knetsch |first4=C. W. |last5=van Leeuwen |first5=H. C. |last6=Lawley |first6=T. D. |last7=Auchtung |first7=J. M. |last8=Britton |first8=R. A. |title=Dietary trehalose enhances virulence of epidemic ''Clostridium difficile'' |journal=Nature |date=January 2018 |volume=553 |issue=7688 |pages=291–294 |doi=10.1038/nature25178 | pmid = 29310122 | pmc = 5984069 | bibcode = 2018Natur.553..291C }}</ref> but this finding was disputed in 2019.<ref name="Eyre">{{cite journal | last1=Eyre | first1=David W. | last2=Didelot | first2=Xavier | last3=Buckley | first3=Anthony M. | last4=Freeman | first4=Jane | last5=Moura | first5=Ines B. | last6=Crook | first6=Derrick W. | last7=Peto | first7=Tim E.A. | last8=Walker | first8=A. Sarah | last9=Wilcox | first9=Mark H. | last10=Dingle | first10=Kate E. | title=Clostridium difficile trehalose metabolism variants are common and not associated with adverse patient outcomes when variably present in the same lineage | journal=eBioMedicine| volume=43 | year=2019 | issn=2352-3964 | doi=10.1016/j.ebiom.2019.04.038 | pages=347–355|pmid=31036529|pmc=6558026}}</ref>

In 2021, the FDA accepted an [[Investigational New Drug]] (IND) application and granted [[Fast track (FDA)|fast track]] status for an injectable form of trehalose (SLS-005) as a potential treatment for [[Machado-Joseph disease|spinocerebellar ataxia type 3]] (SCA3).<ref name="Park 2021">{{cite web |last=Park |first=Brian |title=Trehalose Fast Tracked for ''Spinocerebellar Ataxia'' |website=MPR |date=8 November 2021 |url=https://www.empr.com/home/news/drugs-in-the-pipeline/trehalose-fast-tracked-for-spinocerebellar-ataxia/ |access-date=14 November 2023}}</ref><ref name="PN 2021">{{cite web |title=FDA Accepts Investigational New Drug Application and Grants Fast Track Designation of Trehalose for ''Spinocerebellar Ataxia Treatment'' |website=Practical Neurology |date=12 November 2021 |url=https://practicalneurology.com/news/fda-accepts-investigational-new-drug-application-and-grants-fast-track-designation-of-trehalose-for-spinocerebellar-ataxia-treatment |access-date=14 November 2023}}</ref>

==History==
In 1832, H.A.L. Wiggers discovered trehalose in an [[ergot]] of rye,<ref>{{cite journal |last1=Wiggers |first1=H. A. L. |title=Untersuchung über das Mutterkorn, Secale cornutum |journal=Annalen der Pharmacie |date=January 1832 |volume=1 |issue=2 |pages=129–182 |doi=10.1002/jlac.18320010202 |language=de |url=https://zenodo.org/record/1426894 }}</ref> and in 1859 [[Marcellin Berthelot]] isolated it from ''Trehala manna'', a substance made by [[weevil]]s and named it trehalose.<ref>{{cite journal |last1=Tillequin |first1=François |title=Le Tréhala, une drogue à la croisée des chemins |journal=Revue d'histoire de la pharmacie |date=2009 |volume=96 |issue=362 |pages=163–172 |doi=10.3406/pharm.2009.22043 |language=fr | pmid = 20027793}}</ref>

Trehalose has long been known as an [[autophagy]] inducer that acts independently of [[mTOR]].<ref>{{cite journal |last1=Menzies |first1=Fiona M. |last2=Fleming |first2=Angeleen |last3=Rubinsztein |first3=David C. |title=Compromised autophagy and neurodegenerative diseases |journal=Nature Reviews Neuroscience |date=June 2015 |volume=16 |issue=6 |pages=345–357 |doi=10.1038/nrn3961 | pmid = 25991442 | s2cid = 19272817 }}</ref> In 2017, research was published showing that trehalose induces autophagy by activating [[TFEB]],<ref>{{cite journal |last1=Sharma |first1=Jaiprakash |last2=di Ronza |first2=Alberto |last3=Lotfi |first3=Parisa |last4=Sardiello |first4=Marco |title=Lysosomes and Brain Health |journal=Annual Review of Neuroscience |date=8 July 2018 |volume=41 |issue=1 |pages=255–276 |doi=10.1146/annurev-neuro-080317-061804 | pmid = 29661037 | s2cid = 207581692 }}</ref> a protein that acts as a master regulator of the autophagy-[[lysosome]] pathway.<ref>{{cite journal |last1=Sardiello |first1=Marco |title=Transcription factor EB: from master coordinator of lysosomal pathways to candidate therapeutic target in degenerative storage diseases |journal=Annals of the New York Academy of Sciences |date=May 2016 |volume=1371 |issue=1 |pages=3–14 |doi=10.1111/nyas.13131 | pmid = 27299292 | pmc = 5032832 | bibcode = 2016NYASA1371....3S }}</ref>

== See also ==
* [[Biostasis]]
* [[Cryoprotectant]]
* [[Cryptobiosis]]
* [[Freeze drying]]
*[[Lentztrehalose]]
*[[Trehalosamine]]
*[[IMCTA-C14]]

== References ==
{{Reflist}}

== External links ==
*{{Commons category-inline}}
*[https://insider.si.edu/2017/11/next-step-endangered-species-conservation-microwave-dried-sperm-cells/?fbclid=IwAR1VUKwQrZurmEI984aWTwG0Ydnq_oVtbYcg0DBSjdyy9D8J61AKdK3ppgE Trehalose in sperm preservation]
{{Carbohydrates}}

[[Category:Carbohydrates]]
[[Category:Disaccharides]]
[[Category:Types of sugar]]
[[Category:Orphan drugs]]