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| Record Information |
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| Version | 4.0 |
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| Status | Detected and Quantified |
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| Creation Date | 2005-11-16 15:48:42 UTC |
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| Update Date | 2020-06-15 17:04:52 UTC |
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| HMDB ID | HMDB0001372 |
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| Secondary Accession Numbers | |
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| Metabolite Identification |
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| Common Name | Thiamine pyrophosphate |
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| Description | Thiamine pyrophosphate (CAS: 154-87-0) 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 several cell constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defences. The enzymes are also important for the 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 catalyze reactions that 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 the formation of a second carbanion (enamine). This formation 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 a cofactor. The thiamine pyrophosphate dependence of the third step is unique in peroxisomal mammalian enzymology. Human pathology due to a deficient alpha-oxidation is mostly linked to mutations in the gene coding for the second enzyme of the sequence, phytanoyl-CoA hydroxylase (EC 1.14.11.18) (PMID: 12694175 , 11899071 , 9924800 ). |
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| Structure | |
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| Synonyms | | Value | Source |
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| Thiamin diphosphate | ChEBI | | Thiamin pyrophosphate | ChEBI | | Thiamine diphosphate | ChEBI | | THPP | ChEBI | | TPP | ChEBI | | Thiamin diphosphoric acid | Generator | | Thiamin pyrophosphoric acid | Generator | | Thiamine diphosphoric acid | Generator | | Thiamine pyrophosphoric acid | Generator | | Thaimine pyrophosphate | HMDB | | Thiamin-ppi | HMDB | | Thiamine-ppi | HMDB | | Thiamine-pyrophosphate | HMDB | | Cocarboxylase | HMDB | | Berolase | HMDB | | Pyrophosphate, thiamine | HMDB |
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| Chemical Formula | C12H19N4O7P2S |
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| Average Molecular Weight | 425.314 |
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| Monoisotopic Molecular Weight | 425.044967696 |
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| IUPAC Name | 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-{[hydroxy(phosphonooxy)phosphoryl]oxy}ethyl)-4-methyl-1,3-thiazol-3-ium |
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| Traditional Name | thiamin pyrophosphate |
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| CAS Registry Number | 136-09-4 |
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| SMILES | CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N |
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| InChI Identifier | 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 |
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| InChI Key | AYEKOFBPNLCAJY-UHFFFAOYSA-O |
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| Chemical Taxonomy |
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| 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. |
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| Kingdom | Organic compounds |
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| Super Class | Organoheterocyclic compounds |
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| Class | Diazines |
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| Sub Class | Pyrimidines and pyrimidine derivatives |
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| Direct Parent | Thiamine phosphates |
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| Alternative Parents | |
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| Substituents | - Thiamine-phosphate
- Organic pyrophosphate
- 4,5-disubstituted 1,3-thiazole
- Monoalkyl phosphate
- Hydropyrimidine
- Organic phosphoric acid derivative
- Phosphoric acid ester
- Alkyl phosphate
- Imidolactam
- Thiazole
- Azole
- Heteroaromatic compound
- Azacycle
- Organic oxide
- Organic nitrogen compound
- Organopnictogen compound
- Organooxygen compound
- Organonitrogen compound
- Organic oxygen compound
- Hydrocarbon derivative
- Organic cation
- Aromatic heteromonocyclic compound
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| Molecular Framework | Aromatic heteromonocyclic compounds |
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| External Descriptors | |
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| Ontology |
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| Physiological effect | Health effect: |
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| Disposition | Source: Biological location: |
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| Process | Naturally occurring process: |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | Not Available | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | Not Available | Not Available | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| Spectra |
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| | Spectrum Type | Description | Splash Key | View |
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| Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-002b-9734000000-83738512818790cf1cc5 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated) | splash10-004i-0201900000-9ca110d3800e4ebfad43 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated) | splash10-00di-0900000000-dad8835a4b26b1df86c4 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated) | splash10-00di-2900000000-83b0eb52fe05e7097aff | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negative | splash10-00di-0000900000-538ee08c2fc9a905eaad | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negative | splash10-0udi-0309000000-b196fd5684e86907d04e | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negative | splash10-0udi-0409000000-088cf88d5056ce245770 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negative | splash10-004i-9822000000-011b97ebb9fdcebffc93 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negative | splash10-004i-9200000000-2ecd5ee7eb283c5cd990 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive | splash10-004i-0001900000-59ea8d394aed62700202 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive | splash10-00b9-0614900000-08f09a377f03019f4457 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive | splash10-00di-0911000000-de2b56b98b01c6409b09 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive | splash10-00di-0900000000-7d75ca5105912446e47b | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive | splash10-00di-2900000000-d632b8688f17a7a01de0 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ , negative | splash10-00di-0000900000-538ee08c2fc9a905eaad | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ , negative | splash10-0udi-0309000000-b196fd5684e86907d04e | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ , negative | splash10-0udi-0409000000-088cf88d5056ce245770 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ , negative | splash10-004i-9822000000-670f784e69ef56047333 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ , negative | splash10-004i-9200000000-2ecd5ee7eb283c5cd990 | Spectrum | | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QQ , positive | splash10-004i-0001900000-59ea8d394aed62700202 | Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-004i-0100900000-2d5d6c77c0c7e2d2d28a | Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0aba-8146900000-e4efbc495cf0eb380395 | Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0a4j-4911100000-7e4a6eda3f297e8051b7 | Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-00di-0000900000-08198f6dfeaa404b8b0f | Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-001i-9100200000-2d9e7e5d87267ce83dcc | Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-004j-9200000000-a470e5de9f124c159e0e | Spectrum | | 1D NMR | 1H NMR Spectrum | Not Available | Spectrum | | 2D NMR | [1H,13C] 2D NMR Spectrum | Not Available | Spectrum |
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| Biological Properties |
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| Cellular Locations | |
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| Biospecimen Locations | - Blood
- Cerebrospinal Fluid (CSF)
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| Tissue Locations | - Brain
- Erythrocyte
- Fibroblasts
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| Pathways | |
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| Normal Concentrations |
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| Cerebrospinal Fluid (CSF) | Detected and Quantified | 0.0032 +/- 0.0022 uM | Adult (>18 years old) | Both | Normal | | details |
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| Abnormal Concentrations |
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| Blood | Detected and Quantified | 0.034 (0-0.066) uM | Adult (>18 years old) | Not Specified | Cerebrocortical Degeneration | | details | | Cerebrospinal Fluid (CSF) | Detected and Quantified | 0.0025 +/- 0.0017 uM | Adult (>18 years old) | Both | Alzheimer's disease | | details |
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| Associated Disorders and Diseases |
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| Disease References | | Cerebrocortical degeneration |
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- Holtershinken M, Hohling A, Witte B, Scholz H: [Thiamine and its derivates in cattle blood measured by HPLC in healthy animals, in patients suffering from CCN and in their cohorts]. Dtsch Tierarztl Wochenschr. 2007 Jun;114(6):212-8. [PubMed:17642321 ]
| | Alzheimer's disease |
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- Molina JA, Jimenez-Jimenez FJ, Hernanz A, Fernandez-Vivancos E, Medina S, de Bustos F, Gomez-Escalonilla C, Sayed Y: Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease. J Neural Transm (Vienna). 2002 Jul;109(7-8):1035-44. [PubMed:12111441 ]
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| Associated OMIM IDs | |
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| External Links |
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| DrugBank ID | Not Available |
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| Phenol Explorer Compound ID | Not Available |
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| FooDB ID | FDB022584 |
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| KNApSAcK ID | C00019627 |
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| Chemspider ID | 1100 |
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| KEGG Compound ID | C00068 |
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| BioCyc ID | THIAMINE-PYROPHOSPHATE |
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| BiGG ID | 33732 |
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| Wikipedia Link | Thiamine pyrophosphate |
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| METLIN ID | 2832 |
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| PubChem Compound | 1132 |
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| PDB ID | Not Available |
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| ChEBI ID | 9532 |
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| Food Biomarker Ontology | Not Available |
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| VMH ID | THMPP |
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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. |
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| Material Safety Data Sheet (MSDS) | Download (PDF) |
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| General References | - Floridi A, Pupita M, Palmerini CA, Fini C, Alberti Fidanza A: Thiamine pyrophosphate determination in whole blood and erythrocytes by high performance liquid chromatography. Int J Vitam Nutr Res. 1984;54(2-3):165-71. [PubMed:6500839 ]
- Essama-Tjani JC, Guilland JC, Fuchs F, Lombard M, Richard D: Changes in thiamin, riboflavin, niacin, beta-carotene, vitamins, C, A, D and E status of French Elderly Subjects during the first year of institutionalization. Int J Vitam Nutr Res. 2000 Mar;70(2):54-64. [PubMed:10804457 ]
- Warnock LG: The measurement of erythrocyte thiamin pyrophosphate by high-performance liquid chromatography. Anal Biochem. 1982 Nov 1;126(2):394-7. [PubMed:7158773 ]
- Lynch PL, Trimble ER, Young IS: High-performance liquid chromatographic determination of thiamine diphosphate in erythrocytes using internal standard methodology. J Chromatogr B Biomed Sci Appl. 1997 Nov 7;701(1):120-3. [PubMed:9389346 ]
- Naito E, Ito M, Yokota I, Saijo T, Ogawa Y, Kuroda Y: Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency. J Neurol Sci. 2002 Sep 15;201(1-2):33-7. [PubMed:12163191 ]
- Molina JA, Jimenez-Jimenez FJ, Hernanz A, Fernandez-Vivancos E, Medina S, de Bustos F, Gomez-Escalonilla C, Sayed Y: Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease. J Neural Transm (Vienna). 2002 Jul;109(7-8):1035-44. [PubMed:12111441 ]
- Baines M: Improved high performance liquid chromatographic determination of thiamin diphosphate in erythrocytes. Clin Chim Acta. 1985 Nov 29;153(1):43-8. [PubMed:4075519 ]
- Duffy P, Morris H, Neilson G: Thiamin status of a Melanesian population. Am J Clin Nutr. 1981 Aug;34(8):1584-92. [PubMed:7270482 ]
- Kjosen B, Seim SH: The transketolase assay of thiamine in some diseases. Am J Clin Nutr. 1977 Oct;30(10):1591-6. [PubMed:910736 ]
- Winston AP, Jamieson CP, Madira W, Gatward NM, Palmer RL: Prevalence of thiamin deficiency in anorexia nervosa. Int J Eat Disord. 2000 Dec;28(4):451-4. [PubMed:11054793 ]
- Foulon V, Sniekers M, Huysmans E, Asselberghs S, Mahieu V, Mannaerts GP, Van Veldhoven PP, Casteels M: Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids. J Biol Chem. 2005 Mar 18;280(11):9802-12. Epub 2005 Jan 11. [PubMed:15644336 ]
- Levy S, Herve C, Delacoux E, Erlinger S: Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases. Dig Dis Sci. 2002 Mar;47(3):543-8. [PubMed:11911339 ]
- Talwar D, Davidson H, Cooney J, St JO'Reilly D: Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay. Clin Chem. 2000 May;46(5):704-10. [PubMed:10794754 ]
- Fidanza F, Simonetti MS, Floridi A, Codini M, Fidanza R: Comparison of methods for thiamin and riboflavin nutriture in man. Int J Vitam Nutr Res. 1989;59(1):40-7. [PubMed:2722424 ]
- Tate JR, Nixon PF: Measurement of Michaelis constant for human erythrocyte transketolase and thiamin diphosphate. Anal Biochem. 1987 Jan;160(1):78-87. [PubMed:3565758 ]
- Frank T, Bitsch R, Maiwald J, Stein G: High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine. Eur J Clin Pharmacol. 2000 Jun;56(3):251-7. [PubMed:10952481 ]
- Shimon I, Almog S, Vered Z, Seligmann H, Shefi M, Peleg E, Rosenthal T, Motro M, Halkin H, Ezra D: Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995 May;98(5):485-90. [PubMed:7733128 ]
- Lavoie J, Butterworth RF: Reduced activities of thiamine-dependent enzymes in brains of alcoholics in the absence of Wernicke's encephalopathy. Alcohol Clin Exp Res. 1995 Aug;19(4):1073-7. [PubMed:7485819 ]
- Casteels M, Foulon V, Mannaerts GP, Van Veldhoven PP: Alpha-oxidation of 3-methyl-substituted fatty acids and its thiamine dependence. Eur J Biochem. 2003 Apr;270(8):1619-27. [PubMed:12694175 ]
- Singleton CK, Martin PR: Molecular mechanisms of thiamine utilization. Curr Mol Med. 2001 May;1(2):197-207. [PubMed:11899071 ]
- Schenk G, Duggleby RG, Nixon PF: Properties and functions of the thiamin diphosphate dependent enzyme transketolase. Int J Biochem Cell Biol. 1998 Dec;30(12):1297-318. [PubMed:9924800 ]
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