thiamine triphosphate
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| verifiedrevid = 470606262
| ImageFile=Thiamintriphosphat.svg
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|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 17927
| InChI = 1/C12H19N4O10P3S/c1-8-11(30-7-16(8)6-10-5-14-9(2)15-12(10)13)3-4-24-28(20,21)26-29(22,23)25-27(17,18)19/h5,7H,3-4,6H2,1-2H3,(H5-,13,14,15,17,18,19,20,21,22,23)
| InChIKey = IWLROWZYZPNOFC-UHFFFAOYAE
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| StdInChI = 1S/C12H19N4O10P3S/c1-8-11(30-7-16(8)6-10-5-14-9(2)15-12(10)13)3-4-24-28(20,21)26-29(22,23)25-27(17,18)19/h5,7H,3-4,6H2,1-2H3,(H5-,13,14,15,17,18,19,20,21,22,23)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IWLROWZYZPNOFC-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo=3475-65-8
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 464M6AQ7IV
| PubChem=18989
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 18284
| SMILES = Cc1c(sc[n+]1Cc2cnc(nc2N)C)CCOP(=O)(O)OP(=O)(O)OP(=O)(O)[O-]
| MeSHName=Thiamine+triphosphate
}}
|Section2={{Chembox Properties
| Formula=C12H19N4O10P3S
| MolarMass=504.288
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Thiamine triphosphate (ThTP) is a biomolecule found in most organisms including bacteria, fungi, plants and animals.{{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=Cell. Mol. Life Sci. |volume=60 |issue=7 |pages=1477–88 |year=2003 |pmid=12943234 |doi=10.1007/s00018-003-3098-4 |s2cid=25400487 |pmc=11146050 }} Chemically, it is the triphosphate derivative of the vitamin thiamine.
Function
It has been proposed that ThTP has a specific role in nerve excitability,{{Cite journal | pmid=6272323 | pmc=348897 | year=1981 | last1=Matsuda | first1=T | last2=Cooper | first2=JR | title=Thiamine as an integral component of brain synaptosomal membranes | volume=78 | issue=9 | pages=5886–9 | journal=Proceedings of the National Academy of Sciences of the United States of America | doi=10.1073/pnas.78.9.5886| bibcode=1981PNAS...78.5886M | doi-access=free }} but this has never been confirmed and recent results suggest that ThTP probably plays a role in cell energy metabolism.{{cite journal | doi = 10.1074/jbc.M111241200 | title = Molecular Characterization of a Specific Thiamine Triphosphatase Widely Expressed in Mammalian Tissues | year = 2002 | last1 = Lakaye | first1 = B. | journal = Journal of Biological Chemistry | volume = 277 | issue = 16 | pages = 13771–7 | pmid = 11827967 | last2 = Makarchikov | first2 = AF | last3 = Antunes | first3 = AF | last4 = Zorzi | first4 = W | last5 = Coumans | first5 = B | last6 = De Pauw | first6 = E | last7 = Wins | first7 = P | last8 = Grisar | first8 = T | last9 = Bettendorff | first9 = L | doi-access = free }} Low or absent levels of thiamine triphosphate have been found in Leigh's disease.{{Cite journal | pmc = 492163| year = 1975| last1 = Murphy| first1 = J. V.| title = Leigh's disease: Significance of the biochemical changes in brain| journal = Journal of Neurology, Neurosurgery, and Psychiatry| volume = 38| issue = 11| pages = 1100–1103| last2 = Craig| first2 = L.| pmid = 1206418| doi=10.1136/jnnp.38.11.1100}} {{cite journal | doi = 10.1001/archneur.1974.00490400034002 | title = Leigh Disease | journal = Archives of Neurology | volume = 31 | issue = 4 | pages = 220 | year = 1974 | last1 = Murphy | first1 = Jerome V. }}
In E. coli, ThTP is accumulated in the presence of glucose during amino acid starvation. On the other hand, suppression of the carbon source leads to the accumulation, of adenosine thiamine triphosphate (AThTP).
Metabolism
It has been shown that in brain ThTP is synthesized in mitochondria by a chemiosmotic mechanism, perhaps similar to ATP synthase.{{cite journal | doi = 10.1074/jbc.M109.054379 | title = Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and is Coupled to the Respiratory Chain | year = 2009 | last1 = Gangolf | first1 = M. | last2 = Wins | first2 = P. | last3 = Thiry | first3 = M. | last4 = El Moualij | first4 = B. | last5 = Bettendorff | first5 = L. | journal = Journal of Biological Chemistry | volume = 285 | pages = 583–94 | pmid = 19906644 | issue = 1 | pmc = 2804207| doi-access = free }} In mammals, ThTP is hydrolyzed to thiamine pyrophosphate (ThDP) by a specific thiamine-triphosphatase.{{cite journal | doi = 10.1074/jbc.M709675200 | title = Structural Basis for the Catalytic Mechanism of Mammalian 25-kDa Thiamine Triphosphatase | year = 2008 | last1 = Song | first1 = J. | last2 = Bettendorff | first2 = L. | last3 = Tonelli | first3 = M. | last4 = Markley | first4 = J. L. | journal = Journal of Biological Chemistry | volume = 283 | issue = 16 | pages = 10939–48 | pmid = 18276586 | pmc = 2447667| doi-access = free }} It can also be converted into ThDP by thiamine-diphosphate kinase.
History
Thiamine triphosphate (ThTP) was chemically synthesized in 1948 at a time when the only organic triphosphate known was ATP.{{Cite journal |author1=Velluz L., Amiard G. |author2=Bartos J. |name-list-style=amp | year = 1948 |title = Un nouveau derive de phosphorylation de la vitamine=B1, lacide thiamine triphosphorique | journal = J. Bull. Soc. Chim. Fr. | volume = 15 | pages = 871}} The first claim of the existence of ThTP in living organisms was made in rat liver,{{Cite journal |author1=Rossi-Fanelli A., Siliprandi N. |author2=Fasella P. |name-list-style=amp | year = 1952 | title = On the presence of triphosphothiamine (TPT) in the liver | journal = Science | volume = 116 | pages = 711–713 | doi = 10.1126/science.116.3026.711 | pmid = 13028255 | issue = 3026|bibcode=1952Sci...116..711R }} followed by baker’s yeast.{{Cite journal | author = Kiessling K.-H. | year = 1953 | title = Thiamine triphosphate in baker's yeast | journal = Nature | volume = 172 | pages = 1187–1188 | doi = 10.1038/1721187a0 | pmid = 13111284 | issue = 4391| bibcode = 1953Natur.172.1187K | s2cid = 4289038 }} Its presence was later confirmed in rat tissues{{Cite journal |author1=Greiling H. |author2=Kiesow L. |name-list-style=amp | year = 1958 | title = Zur Biochemie der Thiamintriphosphorsäure IV. Das Vorkommen von Thiamintriphosphat im tierischen Organismus | journal = Zeitschrift für Naturforschung B | volume = 13 | pages = 251–252 | doi=10.1515/znb-1958-0412| doi-access = free }} and in plants germs, but not in seeds, where thiamine was essentially unphosphorylated.{{Cite journal | author = Yusa T. | year = 1962 | title = Studies on thiamine triphosphate II. Thiamine triphosphate as phosphate donor | journal = Plant Cell | volume = 3 | pages = 95–103}} In all those studies, ThTP was separated from other thiamine derivatives using a paper chromatographic method, followed by oxidation in fluorescent thiochrome compounds with ferricyanide in alkaline solution. This method is at best semi-quantitative, and the development of liquid chromatographic methods suggested that ThTP represents far less than 10% of total thiamine in animal tissues.{{Cite journal |author1=Rindi G. |author2=de Giuseppe L. |name-list-style=amp | year = 1961 | title = A new chromatographic method for the determination of thiamine and its mono-, di- and triphosphates in animal tissues | journal = Biochem. J. | volume = 78 |issue=3 | pages = 602–606 | pmid = 13741738 | pmc = 1205381 | doi=10.1042/bj0780602}}