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Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), is a thiamine (vitamin B1) derivative which is produced by the enzyme thiamine pyrophosphatase. Thiamine pyrophosphate is a cofactor that is present in all living systems, in which it catalyzes several biochemical reactions. 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.[1]

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

Pyruvate dehydrogenase complex[2]

Pyruvate decarboxylase in ethanol fermentation

Alpha-ketoglutarate dehydrogenase complex

Branched-chain amino acid dehydrogenase complex

2-hydroxyphytanoyl-CoA lyase

Transketolase

Contents

[hide] 1 Chemistry

2 Reaction mechanisms

3 References

4 External links

[edit] Chemistry

The "ylid 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 more favorable. (A compound with positive and negative charges on adjacent atoms is called an ylid or ylide, so sometimes the carbanion form of TPP is referred to as the "ylid form".[1][3]

[edit] Reaction mechanisms

In several reactions, including that of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase, TPP catalyses the reversible 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). It achieves this in four basic steps:

1.The carbanion of the TPP ylid nucleophilically attacks the carbonyl group on the substrate. (This forms a single bond between the TPP and the substrate.)

2.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.

3.In what is essentially the reverse of step two,

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