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{{chembox
| Watchedfields = changed
| verifiedrevid = 470606241
| Name =
| ImageFile = Thiamine diphosphate.png
| ImageSize = 200px
| IUPACName = 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl phosphono hydrogen phosphate
| OtherNames = Thiamine diphosphate
| SystematicName =
| Section1 = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10670483
| ChEBI = 9532
| KEGG = C00068
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q57971654Y
| InChI = 1/C12H17N4OS.ClH.H4O7P2/c1-8-11(3-4-17)18-7-16(8)6-10-5-14-9(2)15-12(10)13;;1-8(2,3)7-9(4,5)6/h5,7,17H,3-4,6H2,1-2H3,(H2,13,14,15);1H;(H2,1,2,3)(H2,4,5,6)/q+1;;/p-1
| InChIKey = NBSUTVXQOGUTJX-REWHXWOFAB
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H17N4OS.ClH.H4O7P2/c1-8-11(3-4-17)18-7-16(8)6-10-5-14-9(2)15-12(10)13;;1-8(2,3)7-9(4,5)6/h5,7,17H,3-4,6H2,1-2H3,(H2,13,14,15);1H;(H2,1,2,3)(H2,4,5,6)/q+1;;/p-1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NBSUTVXQOGUTJX-UHFFFAOYSA-M
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 136-08-3
| PubChem = 1132
| SMILES = Cc2ncc(C[n+]1csc(CCOP(=O)(O)OP(=O)(O)O)c1C)c(N)n2
| MeSHName = Thiamine+pyrophosphate
}}
| Section2 = {{Chembox Properties
| Formula = C12H19N4O7P2S+
| MolarMass = 425.314382 g/mol
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
}}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
| Section4 =
| Section5 =
| Section6 =
}}
'''Thiamine pyrophosphate''' ('''TPP''' or '''ThPP'''), or '''thiamine diphosphate''' ('''ThDP'''), or '''cocarboxylase''' is a [[thiamine]] (vitamin B1) [[Derivative (chemistry)|derivative]] which is produced by the [[enzyme]] [[thiamine diphosphokinase]]. Thiamine pyrophosphate is a [[cofactor (biochemistry)|cofactor]] that is present in all living systems, in which it catalyzes several [[Biochemistry|biochemical]] reactions.

Thiamine pyrophosphate is synthesized in the [[cytosol]] and is required in the cytosol for the activity of transketolase and in the mitochondria for the activity of pyruvate-, oxoglutarate- and branched chain keto acid dehydrogenases. To date, the yeast ThPP carrier (Tpc1p) the human Tpc and the ''[[Drosophila melanogaster]]'' have been identified as being responsible for the mitochondrial transport of ThPP and ThMP. It was first discovered as an [[essential nutrient]] ([[vitamin]]) in humans through its link with the [[peripheral nervous system]] [[disease]] [[beriberi]], which results from a deficiency of thiamine in the [[Diet (nutrition)|diet]].

TPP works as a [[coenzyme]] in many enzymatic reactions, such as:

* [[Pyruvate dehydrogenase]] complex
* [[Pyruvate decarboxylase]] in [[ethanol fermentation]]
* [[Alpha-ketoglutarate dehydrogenase]] complex
* [[Branched-chain amino acid dehydrogenase]] complex
* [[2-hydroxyphytanoyl-CoA lyase]]
* [[Transketolase]]

==Chemistry==
[[Image:TPP-ylide.svg|thumb|right|The "ylide form" of TPP.]]

Chemically, TPP consists of a [[pyrimidine]] ring which is connected to a [[thiazole]] ring, which is in turn connected to a [[pyrophosphate]] (diphosphate) [[functional group]].

The part of TPP molecule that is most commonly involved in reactions is the thiazole ring, which contains [[nitrogen]] and [[sulfur]]. Thus, the thiazole ring is the "reagent portion" of the molecule. The C2 of this ring is capable of acting as an [[acid]] by donating its [[proton]] and forming a [[carbanion]]. Normally, reactions that form carbanions are highly unfavorable, but the positive charge on the tetravalent nitrogen just adjacent to the carbanion stabilizes the negative charge, making the reaction much more favorable. A compound with positive and negative charges on adjacent atoms is called an [[ylide]], so sometimes the carbanion form of TPP is referred to as the "ylide form".

==Reaction mechanisms==
In several reactions, including that of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase, TPP catalyses the reversible decarboxylation reaction (aka cleavage of a substrate compound at a carbon-carbon bond connecting a [[carbonyl group]] to an adjacent reactive group—usually a [[carboxylic acid]] or an [[Alcohol (chemistry)|alcohol]]). It achieves this in four basic steps:

#The carbanion of the TPP ylid [[nucleophilic attack|nucleophilically attacks]] the carbonyl group on the substrate. (This forms a single bond between the TPP and the substrate.)
#The target bond on the substrate is broken, and its electrons are pushed towards the TPP. This creates a double bond between the substrate carbon and the TPP carbon and pushes the electrons in the N-C double bond in TPP entirely onto the nitrogen atom, reducing it from a positive to neutral form.
#In what is essentially the reverse of step two, the electrons push back in the opposite direction forming a new bond between the substrate carbon and another atom. (In the case of the decarboxylases, this creates a new carbon-hydrogen bond. In the case of transketolase, this attacks a new substrate molecule to form a new carbon-carbon bond.)
#In what is essentially the reverse of step one, the TPP-substrate bond is broken, reforming the TPP ylid and the substrate carbonyl.

[[File:TPP Mechanism.svg|TPP Mechanism]]

<gallery mode=packed style="text-align:left">
Image:TPP_thiazolium.svg|The TPP thiazolium ring can be deprotonated at C2 to become an ylid.
Image:Thiamine pyrophosphate ng.png|A full view of TPP. The arrow indicates the acidic proton.
</gallery>

==See also==
* [[TPP riboswitch]]

==External links==
*[http://www.uic.edu/classes/phar/phar332/Clinical_Cases/vitamin%20cases/thiamin/thiamin_pyrophosphate.htm UIC.edu]

{{Enzyme cofactors}}

{{二次利用|date=3 November 2023}}
[[Category:Cofactors]]
[[Category:Organophosphates]]
[[Category:Thiazoles]]
[[Category:Pyrimidines]]
[[Category:Thiamine]]
[[Category:Pyrophosphates]]

Thiamine pyrophosphate/en - Revision history

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