Thiamine pyrophosphate/ja: Difference between revisions

'''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]].

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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]]

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.

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==See also==

* [[TPP riboswitch]]

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==External links==

{{Enzyme cofactors}}