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===Thiamine pyrophosphate=== {{main|thiamine pyrophosphate}} <div class="skin-invert-image"> {{multiple image | align = right | direction = vertical | width = 220 | header = | image1 = Thiamine_diphosphate_coloured.svg | caption1 = Thiamine pyrophosphate (TPP) | image2 = TPP-ylide.svg | caption2 = The ylide form of TPP }} </div> 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>
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