Editing Thiamine (section)

== Biological functions ==
[[Image:Thiamine monophosphate coloured.svg|thumb|class=skin-invert-image|Thiamine monophosphate (ThMP)]]
Five natural thiamine phosphate derivatives are known: [[thiamine monophosphate]] (ThMP), thiamine pyrophosphate (TPP), [[thiamine triphosphate]] (ThTP), [[adenosine thiamine diphosphate]] (AThDP) and [[adenosine thiamine triphosphate]] (AThTP).<ref name=lpi/> They are involved in many cellular processes.<ref name=Fitzpatrick>{{cite journal | vauthors = Fitzpatrick TB, Chapman LM | title = The importance of thiamine (vitamin B<sub>1</sub>) in plant health: From crop yield to biofortification | journal = The Journal of Biological Chemistry | volume = 295 | issue = 34 | pages = 12002–13 | date = August 2020 | pmid = 32554808 | pmc = 7443482 | doi = 10.1074/jbc.REV120.010918 | doi-access = free }}</ref> The best-characterized form is TPP, a [[coenzyme]] in the [[catabolism]] of sugars and amino acids. While its role is well-known, the non-coenzyme action of thiamine and derivatives may be realized through binding to proteins which do not use that mechanism.<ref name="nature.com">{{cite journal | vauthors = Mkrtchyan G, Aleshin V, Parkhomenko Y, Kaehne T, Di Salvo ML, Parroni A, Contestabile R, Vovk A, Bettendorff L, Bunik V | title = Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis | journal = Scientific Reports | volume = 5 | page = 12583 | date = July 2015 | pmid = 26212886 | pmc = 4515825 | doi = 10.1038/srep12583 | bibcode = 2015NatSR...512583M | doi-access = free }}</ref> No physiological role is known for the monophosphate except as an intermediate in cellular conversion of thiamine to the di- and triphosphates.<ref name=Lons2006/>

===Thiamine pyrophosphate===
{{main|thiamine pyrophosphate}}
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 | image1 = Thiamine_diphosphate_coloured.svg
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Thiamine pyrophosphate (TPP), also called thiamine diphosphate (ThDP), participates as a coenzyme in metabolic reactions, including those in which [[umpolung|polarity inversion]] takes place.<ref name=lpi/><ref>{{Cite journal |vauthors=Boluda CJ, Juncá C, Soto E, de la Cruz D, Peña A |date=13 December 2019 |title=Umpolung in reactions catalyzed by thiamine pyrophosphate dependent enzymes |url=https://revistas.intec.edu.do/index.php/cienacli/article/view/1578 |journal=Ciencia, Ambiente y Clima |language=es |volume=2 |issue=2 |pages=27–42 |doi=10.22206/cac.2019.v2i2.pp27-42 |s2cid=213836801 |issn=2636-2333 |doi-access=free |access-date=1 December 2022 |archive-date=1 December 2022 |archive-url=https://web.archive.org/web/20221201152253/https://revistas.intec.edu.do/index.php/cienacli/article/view/1578 |url-status=live }}</ref> Its synthesis is catalyzed by the enzyme [[thiamine diphosphokinase]] according to the reaction thiamine + ATP → TPP + AMP (EC 2.7.6.2).<ref name=lpi/> However, recent findings reveal that uridine 5′-triphosphate (UTP), rather than ATP, is the preferred substrate for TPP synthesis in cells, with TPK1 showing a ~10-fold higher affinity for UTP.<ref name="Sahu2024">{{cite journal | vauthors = Sahu U, Villa E, Reczek CR, Zhao Z, O'Hara BP, Torno MD, Mishra R, Shannon WD, Asara JM, Gao P, Shilatifard A, Chandel NS, Ben-Sahra I | title = Pyrimidines maintain mitochondrial pyruvate oxidation to support de novo lipogenesis | journal = Science | volume = 383 | issue = 6690 | pages = 1484–1492 | date = March 2024 | pmid = 38547260 | doi = 10.1126/science.adh2771 | pmc = 11325697 | bibcode = 2024Sci...383.1484S }}</ref> TPP is a [[coenzyme]] for several enzymes that catalyze the transfer of two-carbon units and in particular the [[dehydrogenation]] ([[decarboxylation]] and subsequent conjugation with [[coenzyme A]]) of 2-oxoacids (alpha-keto acids).<ref name=lpi/> The mechanism of action of TPP as a coenzyme relies on its ability to form an [[ylide]].<ref>{{cite journal | vauthors = Ciszak EM, Korotchkina LG, Dominiak PM, Sidhu S, Patel MS | title = Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase | journal = The Journal of Biological Chemistry | volume = 278 | issue = 23 | pages = 21240–46 | date = June 2003 | pmid = 12651851 | doi = 10.1074/jbc.M300339200 | doi-access = free | hdl = 2060/20030106063 | hdl-access = free }}</ref> Examples include:
* Present in most species
** [[pyruvate dehydrogenase]] and 2-[[oxoglutarate dehydrogenase]] (also called [[alpha-ketoglutarate dehydrogenase|α-ketoglutarate dehydrogenase]])
** [[branched-chain α-keto acid dehydrogenase]]
** [[2-hydroxyphytanoyl-CoA lyase]]
** [[transketolase]]
* Present in some species:
** [[pyruvate decarboxylase]] (in [[yeast]])
** several additional [[bacteria]]l enzymes

The enzymes transketolase, pyruvate dehydrogenase (PDH), and 2-oxoglutarate dehydrogenase (OGDH) are important in [[carbohydrate metabolism]].<ref name=lpi/> PDH links glycolysis to the [[citric acid cycle]]. OGDH catalyzes the overall conversion of [[Alpha-Ketoglutaric acid|2-oxoglutarate]] (alpha-ketoglutarate) to [[succinyl-CoA]] and CO<sub>2</sub> during the [[citric acid cycle]].<ref name=lpi/>  The reaction catalyzed by OGDH is a rate-limiting step in the citric acid cycle. The cytosolic enzyme transketolase is central to the [[pentose phosphate pathway]], a major route for the biosynthesis of the pentose [[sugar]]s [[deoxyribose]] and [[ribose]].<ref name=lpi/> The mitochondrial PDH and OGDH are part of biochemical pathways that result in the generation of [[adenosine triphosphate]] (ATP), which is the main energy transfer molecule for the cell.<ref name=lpi/> In the nervous system, PDH is also involved in the synthesis of [[myelin]] and the neurotransmitter [[acetylcholine]].<ref name="ModNutr2006">{{cite book | vauthors = Butterworth RF | chapter = Thiamin | veditors = Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ | title = Modern Nutrition in Health and Disease | edition = 10th | location = Baltimore | publisher = Lippincott Williams & Wilkins | date = 2006 }}</ref>

=== Thiamine triphosphate ===
[[File:Thiamine triphosphate coloured.svg|thumb|right|class=skin-invert-image|Thiamine triphosphate (ThTP)]]
ThTP is implicated in [[chloride channel]] activation in the neurons of mammals and other animals, although its role is not well understood.<ref name=Lons2006/> ThTP has been found in bacteria, fungi and plants, suggesting that it has other cellular roles.<ref>{{cite journal | vauthors = Makarchikov AF, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P, Grisar T, Bettendorff L | title = Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals | journal = Cellular and Molecular Life Sciences | volume = 60 | issue = 7 | pages = 1477–88 | date = July 2003 | pmid = 12943234 | doi = 10.1007/s00018-003-3098-4 | s2cid = 25400487 | pmc = 11146050 }}</ref> In ''[[Escherichia coli]]'', it is implicated in the response to amino acid starvation.<ref name="Bettendorff2021"/>

===Adenosine derivatives===
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 | image1 = Adenosine_thiamine_diphosphate_coloured.svg
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 | image2 = Adenosine_thiamine_triphosphate_coloured.svg
 | caption2 = Adenosine thiamine triphosphate (AThTP)
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AThDP exists in small amounts in vertebrate liver, but its role remains unknown.<ref name="Bettendorff2021">{{cite journal |vauthors=Bettendorff L |title=Update on Thiamine Triphosphorylated Derivatives and Metabolizing Enzymatic Complexes |journal=Biomolecules |volume=11 |issue=11 |date=November 2021 |page=1645 |pmid=34827643 |pmc=8615392 |doi=10.3390/biom11111645 |doi-access=free }}</ref>

AThTP is present in ''E. coli'', where it accumulates as a result of carbon starvation. In this bacterium, AThTP may account for up to {{Percentage|20}} of total thiamine. It also exists in lesser amounts in [[yeast]], roots of higher plants and animal tissue.<ref name="Bettendorff2021"/>