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Human Metabolome Database Version 3.5

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Showing metabocard for Thiamine pyrophosphate (HMDB01372)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:10:25 -0700
HMDB ID HMDB01372
Secondary Accession Numbers None
Metabolite Identification
Common Name Thiamine pyrophosphate
Description Thiamine pyrophosphate 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, including neurotransmitters, 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. 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 Link_out, 11899071 Link_out, 9924800 Link_out).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. Thaimine pyrophosphate
  2. Thiamin diphosphate
  3. Thiamin pyrophosphate
  4. Thiamin-PPi
  5. Thiamine diphosphate
  6. Thiamine pyrophosphate
  7. Thiamine-PPi
  8. Thiamine-pyrophosphate
  9. ThPP
  10. TPP
Chemical Formula C12H19N4O7P2S
Average Molecular Weight 425.314
Monoisotopic Molecular Weight 425.044967696
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 thiamine diphosphate
CAS Registry Number 154-87-0
SMILES CC1=C(CCO[P@](O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N
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
InChI Key AYEKOFBPNLCAJY-UHFFFAOYSA-O
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Heteropolycyclic Compounds
Class Thiamines
Sub Class Thiamine Phosphates
Other Descriptors
  • 1,3-thiazolium cation(ChEBI)
  • Thiamines
  • thiamine phosphate(ChEBI)
Substituents
  • Aminopyrimidine
  • Organic Hypophosphite
  • Organic Phosphite
  • Organic Pyrophosphate
  • Phosphoric Acid Ester
  • Pyrimidine
  • Thiazole
Direct Parent Thiamine Phosphates
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Thiamine metabolism
Application Not Available
Cellular locations
  • Cytoplasm
  • Mitochondria
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.15 g/L ALOGPS
LogP -1.21 ALOGPS
LogP -5.8 ChemAxon
LogS -3.48 ALOGPS
pKa (strongest acidic) 1.78 ChemAxon
pKa (strongest basic) 5.53 ChemAxon
Hydrogen Acceptor Count 8 ChemAxon
Hydrogen Donor Count 4 ChemAxon
Polar Surface Area 168.97 A2 ChemAxon
Rotatable Bond Count 8 ChemAxon
Refractivity 95.15 ChemAxon
Polarizability 36.96 ChemAxon
Formal Charge 1 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Fibroblasts
  • Erythrocyte
  • Brain
Pathways
Name SMPDB Link KEGG Link
Thiamine Metabolism SMP00076 map00730 Link_out
Valine, Leucine and Isoleucine Degradation SMP00032 map00280 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Comments
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
0.0032 +/- 0.0022 uM Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
0.034 (0-0.066) uM Adult (>18 years old) Not Specified Cerebrocortical Degeneration Cerebrocortical degeneration of...
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
0.0025 +/- 0.0017 uM Adult (>18 years old) Both Alzheimer's disease Not Available
Associated Disorders and Diseases
Disease References
Cerebrocortical degeneration
  • 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 Link_out
    Alzheimer's disease
    • 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. 2002 Jul;109(7-8):1035-44. Pubmed: 12111441 Link_out
      Associated OMIM IDs
      DrugBank ID Not Available
      Phenol Explorer Compound ID Not Available
      Phenol Explorer Metabolite ID Not Available
      FoodDB ID FDB022584
      KNApSAcK ID Not Available
      Chemspider ID 1100 Link_out
      KEGG Compound ID C00068 Link_out
      BioCyc ID 2-(alpha-lactyl)-thpp Link_out
      BiGG ID 33732 Link_out
      Wikipedia Link Thiamine pyrophosphate Link_out
      NuGOwiki Link HMDB01372 Link_out
      Metagene Link HMDB01372 Link_out
      METLIN ID 2832 Link_out
      PubChem Compound 1132 Link_out
      PDB ID TPP Link_out
      ChEBI ID 9532 Link_out
      References
      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)
      General References
      1. 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 Link_out
      2. 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 Link_out
      3. Warnock LG: The measurement of erythrocyte thiamin pyrophosphate by high-performance liquid chromatography. Anal Biochem. 1982 Nov 1;126(2):394-7. Pubmed: 7158773 Link_out
      4. 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 Link_out
      5. 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 Link_out
      6. 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. 2002 Jul;109(7-8):1035-44. Pubmed: 12111441 Link_out
      7. 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 Link_out
      8. Duffy P, Morris H, Neilson G: Thiamin status of a Melanesian population. Am J Clin Nutr. 1981 Aug;34(8):1584-92. Pubmed: 7270482 Link_out
      9. Kjosen B, Seim SH: The transketolase assay of thiamine in some diseases. Am J Clin Nutr. 1977 Oct;30(10):1591-6. Pubmed: 910736 Link_out
      10. 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 Link_out
      11. 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 Link_out
      12. 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 Link_out
      13. 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 Link_out
      14. 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 Link_out
      15. 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 Link_out
      16. 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 Link_out
      17. 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 Link_out
      18. 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 Link_out
      Enzymes
      Name: Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
      Reactions:
      • pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2 [RN:R01699]
      Gene Name: PDHB
      Uniprot ID: P11177 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
      Reactions:
      • pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2 [RN:R01699]
      Gene Name: PDHA1
      Uniprot ID: P08559 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial
      Reactions:
      • pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2 [RN:R01699]
      Gene Name: PDHA2
      Uniprot ID: P29803 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial
      Reactions:
      • 3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO2 [RN:R01701]
      Gene Name: BCKDHB
      Uniprot ID: P21953 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
      Reactions:
      • 3-methyl-2-oxobutanoate + [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] lipoyllysine = [dihydrolipoyllysine-residue (2-methylpropanoyl)transferase] S-(2-methylpropanoyl)dihydrolipoyllysine + CO2 [RN:R01701]
      Gene Name: BCKDHA
      Uniprot ID: P12694 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: 2-oxoglutarate dehydrogenase, mitochondrial
      Reactions:
      • 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2 [RN:R01700]
      Gene Name: OGDH
      Uniprot ID: Q02218 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Thiamin pyrophosphokinase 1
      Reactions:
      • ATP + thiamine = AMP + thiamine diphosphate [RN:R00619]
      Gene Name: TPK1
      Uniprot ID: Q9H3S4 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Transketolase-like protein 1
      Reactions:
      • sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate [RN:R01641]
      Gene Name: TKTL1
      Uniprot ID: P51854 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Transketolase
      Reactions:
      • sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate [RN:R01641]
      Gene Name: TKT
      Uniprot ID: P29401 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Ectonucleoside triphosphate diphosphohydrolase 5
      Reactions:
      • a nucleoside diphosphate + H2O = a nucleotide + phosphate [RN:R00329]
      Gene Name: ENTPD5
      Uniprot ID: O75356 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Thiamine-triphosphatase
      Reactions:
      • thiamine triphosphate + H2O = thiamine diphosphate + phosphate [RN:R00618]
      Gene Name: THTPA
      Uniprot ID: Q9BU02 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Transketolase-like protein 2
      Reactions:
      • sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-ribose 5-phosphate + D-xylulose 5-phosphate [RN:R01641]
      Gene Name: TKTL2
      Uniprot ID: Q9H0I9 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Acetolactate synthase-like protein
      Reactions:
        Gene Name: ILVBL
        Uniprot ID: A1L0T0 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Name: 2-hydroxyacyl-CoA lyase 1
        Reactions:
          Gene Name: HACL1
          Uniprot ID: Q9UJ83 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Probable 2-oxoglutarate dehydrogenase E1 component DHKTD1, mitochondrial
          Reactions:
          • 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO2 [RN:R01700]
          Gene Name: DHTKD1
          Uniprot ID: Q96HY7 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: 2-oxoglutarate dehydrogenase-like, mitochondrial
          Reactions:
            Gene Name: OGDHL
            Uniprot ID: Q9ULD0 Link_out
            Protein Sequence: FASTA
            Gene Sequence: FASTA