Thiamine pyrophosphate

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Thiamine pyrophosphate
Names
IUPAC name
2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl phosphono hydrogen phosphate
Other names
Thiamine diphosphate
Identifiers
3D model (
JSmol
)
ChEBI
ChemSpider
KEGG
MeSH Thiamine+pyrophosphate
UNII
  • InChI=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 checkY
    Key: NBSUTVXQOGUTJX-UHFFFAOYSA-M checkY
  • 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
    Key: NBSUTVXQOGUTJX-REWHXWOFAB
  • Cc2ncc(C[n+]1csc(CCOP(=O)(O)OP(=O)(O)O)c1C)c(N)n2
Properties
C12H19N4O7P2S+
Molar mass 425.314382 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

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

Thiamine pyrophosphate is synthesized in the

beriberi, which results from a deficiency of thiamine in the diet.[5]

TPP works as a

coenzyme
in many enzymatic reactions, such as:

Chemistry

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.[7] 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.[7] 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".[5][8]

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). 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, 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.)
  4. In what is essentially the reverse of step one, the TPP-substrate bond is broken, reforming the TPP ylid and the substrate carbonyl.

TPP Mechanism

  • The TPP thiazolium ring can be deprotonated at C2 to become an ylid.
    The TPP thiazolium ring can be deprotonated at C2 to become an ylid.
  • A full view of TPP. The arrow indicates the acidic proton.
    A full view of TPP. The arrow indicates the acidic proton.

See also

References

  1. PMID 8834846
    .
  2. PMID 12411483
    .
  3. PMID 20121944
    .
  4. PMID 17035501
    .
  5. ^
    ISBN 978-0-495-28069-9.{{cite book}}: CS1 maint: multiple names: authors list (link
    )
  6. ^ "PDBs for Biochemistry". Georgia State University. Archived from the original on 2011-07-16. Retrieved 2009-02-07.
  7. ^
    ISBN 978-0-08-045382-8
    , retrieved 2020-12-16
  8. ISBN 978-0-470-12930-2
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Thiamine_pyrophosphate&oldid=1183335083"