Thiamine pyrophosphate (ECMDB01372) (M2MDB000361)
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| Version | 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2012-05-31 13:51:11 -0600 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2015-09-13 12:56:11 -0600 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identification | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Name: | Thiamine pyrophosphate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Thiamine pyrophosphate (TPP) is the active form of thiamine, and it serves as a cofactor for several enzymes involved primarily in carbohydrate catabolism. The enzymes are important in the biosynthesis of a number of cell constituents and for the production of reducing equivalents used in oxidant stress defenses and in biosyntheses and for synthesis of pentoses used as nucleic acid precursors. The chemical structure of TPP is that of an aromatic methylaminopyrimidine ring, linked via a methylene bridge to a methylthiazolium ring with a pyrophosphate group attached to a hydroxyethyl side chain. In non-enzymatic model studies it has been demonstrated that the thiazolium ring can catalyse reactions which are similar to those of TPP-dependent enzymes but several orders of magnitude slower. Using infrared and NMR spectrophotometry it has been shown that the dissociation of the proton from C2 of the thiazolium ring is necessary for catalysis; the abstraction of the proton leads to the formation of a carbanion (ylid) with the potential for a nucleophilic attack on the carbonyl group of the substrate. In all TPP-dependent enzymes the abstraction of the proton from the C2 atom is the first step in catalysis, which is followed by a nucleophilic attack of this carbanion on the substrate. Subsequent cleavage of a C-C bond releases the first product with formation of a second carbanion (2-greek small letter alpha-carbanion or enamine). The formation of this 2-greek small letter alpha-carbanion is the second feature of TPP catalysis common to all TPP-dependent enzymes. Depending on the enzyme and the substrate(s), the reaction intermediates and products differ. Methyl-branched fatty acids, as phytanic acid, undergo peroxisomal beta-oxidation in which they are shortened by 1 carbon atom. This process includes four steps: activation, 2-hydroxylation, thiamine pyrophosphate dependent cleavage and aldehyde dehydrogenation. In the third step, 2-hydroxy-3-methylacyl-CoA is cleaved in the peroxisomal matrix by 2-hydroxyphytanoyl-CoA lyase (2-HPCL), which uses thiamine pyrophosphate (TPP) as cofactor. (PMID: 12694175, 11899071, 9924800) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structure |  | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms: |
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| Chemical Formula: | C12H19N4O7P2S | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Weight: | Average: 425.314 Monoisotopic: 425.044967696 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key: | AYEKOFBPNLCAJY-UHFFFAOYSA-O | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI: | InChI=1S/C12H18N4O7P2S/c1-8-11(3-4-22-25(20,21)23-24(17,18)19)26-7-16(8)6-10-5-14-9(2)15-12(10)13/h5,7H,3-4,6H2,1-2H3,(H4-,13,14,15,17,18,19,20,21)/p+1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAS number: | 154-87-0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name: | 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-{[hydroxy(phosphonooxy)phosphoryl]oxy}ethyl)-4-methyl-1,3-thiazol-3-ium | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Traditional IUPAC Name: | thiamin pyrophosphate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SMILES: | CC1=C(CCO[P@](O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of organic compounds known as thiamine phosphates. These are thiamine derivatives in which the hydroxyl group of the ethanol moiety is substituted by a phosphate group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Organoheterocyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Diazines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Pyrimidines and pyrimidine derivatives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Thiamine phosphates | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Substituents |
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| Molecular Framework | Aromatic heteromonocyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors |
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| Physical Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State: | Solid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Charge: | -1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Melting point: | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties: |
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| Predicted Properties |
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| Biological Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations: | Cytoplasm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Reactions: | Adenosine triphosphate + Thiamine monophosphate <> ADP + Thiamine pyrophosphate Water + Thiamine pyrophosphate > Hydrogen ion + Phosphate + Thiamine monophosphate Pyruvic acid + Thiamine pyrophosphate <> 2-(a-Hydroxyethyl)thiamine diphosphate + Carbon dioxide alpha-Ketoglutarate + Thiamine pyrophosphate <> 3-carboxy-1-hydroxypropylthiamine diphosphate + Carbon dioxide 2-Acetolactate + Thiamine pyrophosphate <> 2-(a-Hydroxyethyl)thiamine diphosphate + Pyruvic acid 2-(a-Hydroxyethyl)thiamine diphosphate + Enzyme N6-(lipoyl)lysine <> [Dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + Thiamine pyrophosphate 3-carboxy-1-hydroxypropylthiamine diphosphate + Enzyme N6-(lipoyl)lysine <> [Dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + Thiamine pyrophosphate (S)-2-Acetolactate + Thiamine pyrophosphate <> 2-(a-Hydroxyethyl)thiamine diphosphate + Pyruvic acid 2-Ketobutyric acid + 2-(a-Hydroxyethyl)thiamine diphosphate <> 2-Aceto-2-hydroxy-butyrate + Thiamine pyrophosphate 2-(a-Hydroxyethyl)thiamine diphosphate + Pyruvate-dehydrogenase-lipoate > Thiamine pyrophosphate + Pyruvate-dehydrogenase-acetylDHlipoyl Hydrogen ion + Pyruvic acid + Thiamine pyrophosphate > 2-(a-Hydroxyethyl)thiamine diphosphate + Carbon dioxide Hydrogen ion + Thiamine pyrophosphate + ADP <> adenosine thiamine triphosphate + Phosphate Thiamine monophosphate + Adenosine triphosphate > Thiamine pyrophosphate + ADP TDP-Fuc4NAc + Und-PP-GlcNAc-ManNAcA > Thiamine pyrophosphate + Und-PP-GlcNAc-ManNAcA-Fuc4NAc Thiamine monophosphate + Adenosine triphosphate + Thiamine monophosphate > Thiamine pyrophosphate + Adenosine diphosphate + ADP Adenosine triphosphate + Thiamine monophosphate <> ADP + Thiamine pyrophosphate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SMPDB Pathways: |
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| Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Synthesis Reference: | Zabrodskaya, S. V.; Oparin, D. A.; Ostrovskii, Yu. M. Selective synthesis of thiamine diphosphate. Zhurnal Obshchei Khimii (1989), 59(1), 226-7. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Material Safety Data Sheet (MSDS) | Download (PDF) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Enzymes
- General function:
- Involved in magnesium ion binding
- Specific function:
- 2 pyruvate = 2-acetolactate + CO(2)
- Gene Name:
- ilvI
- Uniprot ID:
- P00893
- Molecular weight:
- 62984
Reactions
| 2 pyruvate = 2-acetolactate + CO(2). |
- General function:
- Involved in acetolactate synthase activity
- Specific function:
- 2 pyruvate = 2-acetolactate + CO(2)
- Gene Name:
- ilvH
- Uniprot ID:
- P00894
- Molecular weight:
- 17977
Reactions
| 2 pyruvate = 2-acetolactate + CO(2). |
- General function:
- Involved in magnesium ion binding
- Specific function:
- 2 pyruvate = 2-acetolactate + CO(2)
- Gene Name:
- ilvB
- Uniprot ID:
- P08142
- Molecular weight:
- 60440
Reactions
| 2 pyruvate = 2-acetolactate + CO(2). |
- General function:
- Involved in amino acid binding
- Specific function:
- 2 pyruvate = 2-acetolactate + CO(2)
- Gene Name:
- ilvN
- Uniprot ID:
- P0ADF8
- Molecular weight:
- 11106
Reactions
| 2 pyruvate = 2-acetolactate + CO(2). |
- General function:
- Involved in acetolactate synthase activity
- Specific function:
- 2 pyruvate = 2-acetolactate + CO(2)
- Gene Name:
- ilvM
- Uniprot ID:
- P0ADG1
- Molecular weight:
- 9703
Reactions
| 2 pyruvate = 2-acetolactate + CO(2). |
- General function:
- Involved in hydrolase activity
- Specific function:
- Catalyzes the hydrolysis of 4-amino-2-methyl-5- hydroxymethylpyrimidine pyrophosphate (HMP-PP) to 4-amino-2- methyl-5-hydroxymethylpyrimidine phosphate (HMP-P), and hydrolysis of thiamine pyrophosphate (TPP) to thiamine monophosphate (TMP). Can hydrolyze other substrates such as MeO-HMP-PP, CF(3)-HMP-PP and MeO-TPP. Is also a non-specific nucleoside tri- and diphosphatase that releases inorganic orthophosphate
- Gene Name:
- nudJ
- Uniprot ID:
- P0AEI6
- Molecular weight:
- 17433
- General function:
- Involved in oxoglutarate dehydrogenase (succinyl-transferring) activity
- Specific function:
- The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). It contains multiple copies of three enzymatic components:2- oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3)
- Gene Name:
- sucA
- Uniprot ID:
- P0AFG3
- Molecular weight:
- 105061
Reactions
| 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO(2). |
- General function:
- Involved in oxidoreductase activity
- Specific function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It contains multiple copies of three enzymatic components:pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3)
- Gene Name:
- aceE
- Uniprot ID:
- P0AFG8
- Molecular weight:
- 99668
Reactions
| Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO(2). |
- General function:
- Involved in catalytic activity
- Specific function:
- ATP + thiamine phosphate = ADP + thiamine diphosphate
- Gene Name:
- thiL
- Uniprot ID:
- P0AGG0
- Molecular weight:
- 35070
Reactions
| ATP + thiamine phosphate = ADP + thiamine diphosphate. |
- General function:
- Involved in fucosyltransferase activity
- Specific function:
- Catalyzes the synthesis of Und-PP-GlcNAc-ManNAcA-Fuc4NAc (Lipid III), the third lipid-linked intermediate involved in ECA synthesis
- Gene Name:
- wecF
- Uniprot ID:
- P56258
- Molecular weight:
- 40639
Reactions
| TDP-Fuc4NAc + Und-PP-GlcNAc-ManNAcA = TDP + Und-PP-GlcNAc-ManNAcA-Fuc4NAc. |