thiamin pyrophosphokinase


Summary: An enzyme that catalyzes the formation of thiamine pyrophosphate from ATP and thiamine. EC

Top Publications

  1. Voskoboyev A, Ostrovsky Y. Thiamin pyrophosphokinase: structure, properties, and role in thiamin metabolism. Ann N Y Acad Sci. 1982;378:161-76 pubmed
  2. Timm D, Liu J, Baker L, Harris R. Crystal structure of thiamin pyrophosphokinase. J Mol Biol. 2001;310:195-204 pubmed
    ..TPP synthesis in eukaryotes requires thiamin pyrophosphokinase (TPK), which catalyzes the transfer of a pyrophosphate group from ATP to thiamin...
  3. Egoramaiphol S, Henke Saipt A, Klapp Kunsemüller E, Bitsch I. High-performance liquid chromatographic (HPLC) analysis of thiamin pyrophosphokinase activity in rat liver. Int J Vitam Nutr Res. 1991;61:334-8 pubmed
    ..The mobile phase was acetonitrile/potassium phosphate buffer, pH 8.2, and elution was monitored spectrofluorometrically. ..
  4. Onozuka M, Nosaka K. Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase. J Nutr Sci Vitaminol (Tokyo). 2003;49:156-62 pubmed
    b>Thiamin pyrophosphokinase catalyzes the pyrophosphorylation of thiamin to thiamin pyrophosphate in the presence of ATP and Mg2+...
  5. Melnick J, Lis E, Park J, Kinsland C, Mori H, Baba T, et al. Identification of the two missing bacterial genes involved in thiamine salvage: thiamine pyrophosphokinase and thiamine kinase. J Bacteriol. 2004;186:3660-2 pubmed
    ..The genes encoding thiamine kinase in Escherichia coli (ycfN) and thiamine pyrophosphokinase in Bacillus subtilis (yloS) have been identified. This study completes the identification of the thiamine salvage enzymes in bacteria. ..
  6. de Jong L, Meng Y, Dent J, Hekimi S. Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis elegans. Genetics. 2004;168:845-54 pubmed
  7. Nosaka K, Kaneko Y, Nishimura H, Iwashima A. Isolation and characterization of a thiamin pyrophosphokinase gene, THI80, from Saccharomyces cerevisiae. J Biol Chem. 1993;268:17440-7 pubmed
    ..Kaneko, Y., and Iwashima, A. (1991) J. Bacteriol. 173, 2716-2719) shows markedly reduced activity of thiamin pyrophosphokinase (TPK; EC
  8. Fankhauser H, Zurlinden A, Schweingruber A, Edenharter E, Schweingruber M. Schizosaccharomyces pombe thiamine pyrophosphokinase is encoded by gene tnr3 and is a regulator of thiamine metabolism, phosphate metabolism, mating, and growth. J Biol Chem. 1995;270:28457-62 pubmed
    ..Disruption of the tnr3 gene is lethal, and a tnr3 mutant expressing only residual TPK activity grows slowly and shows aberrant morphology. ..
  9. Baker L, Dorocke J, Harris R, Timm D. The crystal structure of yeast thiamin pyrophosphokinase. Structure. 2001;9:539-46 pubmed
    b>Thiamin pyrophosphokinase (TPK) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP)...

More Information


  1. Zhao R, Gao F, Goldman I. Molecular cloning of human thiamin pyrophosphokinase. Biochim Biophys Acta. 2001;1517:320-2 pubmed
    b>Thiamin pyrophosphokinase (TPK, EC catalyses phosphorylation of thiamin to thiamin pyrophosphate, an active enzyme cofactor. Here we describe the cloning of complete human TPK1 cDNA from an adult liver library...
  2. Nosaka K, Onozuka M, Kakazu N, Hibi S, Nishimura H, Nishino H, et al. Isolation and characterization of a human thiamine pyrophosphokinase cDNA. Biochim Biophys Acta. 2001;1517:293-7 pubmed
    ..The chromosome localization of the hTPK1 gene was assigned to 7q34. ..
  3. Ajjawi I, Rodriguez Milla M, Cushman J, Shintani D. Thiamin pyrophosphokinase is required for thiamin cofactor activation in Arabidopsis. Plant Mol Biol. 2007;65:151-62 pubmed
    ..The enzyme thiamin pyrophosphokinase (TPK) catalyzes the conversion of free thiamin to TPP in plants and other eukaryotic organisms and is ..
  4. Eschbach M, Müller I, Gilberger T, Walter R, Wrenger C. The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine. Biol Chem. 2006;387:1583-91 pubmed
    ..To verify the location of the parasite TPK within the cell, immunofluorescence analyses were performed. Co-staining of PfTPK with a GFP marker visualised its cytosolic localisation. ..
  5. Liu J, Timm D, Hurley T. Pyrithiamine as a substrate for thiamine pyrophosphokinase. J Biol Chem. 2006;281:6601-7 pubmed
    ..This structure also provides the first clear picture of the binding pocket for the nucleoside triphosphate and permits the first detailed understanding of the catalytic requirements for catalysis in this enzyme. ..
  6. Matsuda T, Tonomura H, Baba A, Iwata H. Difference in thiamine metabolism between extensor digitorum longus and soleus muscles. Comp Biochem Physiol B. 1989;94:399-403 pubmed
    ..4. Tenotomy had little effect on thiamine phosphate levels and the thiamine-related enzyme activities in rat skeletal muscles. ..
  7. Akinci A, Tezic T, Erturk G, Tarim O, Dalva K. Thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness. Acta Paediatr Jpn. 1993;35:262-6 pubmed
    ..After thiamine therapy was ceased an increase in insulin requirement was observed and macrocytic anemia developed again. ..
  8. Bellyei S, Szigeti A, Boronkai A, Szabo Z, Bene J, Janaky T, et al. Cloning, sequencing, structural and molecular biological characterization of placental protein 20 (PP20)/human thiamin pyrophosphokinase (hTPK). Placenta. 2005;26:34-46 pubmed screening a human placental cDNA library, which encode a 243 amino acid protein, identical to human thiamin pyrophosphokinase (hTPK) as confirmed by protein sequence analysis...
  9. Rapala Kozik M, Go da A, Kujda M. Enzymes that control the thiamine diphosphate pool in plant tissues. Properties of thiamine pyrophosphokinase and thiamine-(di)phosphate phosphatase purified from Zea mays seedlings. Plant Physiol Biochem. 2009;47:237-42 pubmed publisher
    ..The total activities of TPK and TDP phosphatases were similarly decreased when the seedlings were grown under the illumination, suggesting a coordinated regulation of both enzymes to stabilize the pool of the essential coenzyme...
  10. Yuge S, Richter C, Wright Osment M, Nicks D, Saloka S, Tillitt D, et al. Identification of the thiamin pyrophosphokinase gene in rainbow trout: characteristic structure and expression of seven splice variants in tissues and cell lines and during embryo development. Comp Biochem Physiol B Biochem Mol Biol. 2012;163:193-202 pubmed publisher
    b>Thiamin pyrophosphokinase (TPK) converts thiamin to its active form, thiamin diphosphate. In humans, TPK expression is down-regulated in some thiamin deficiency related syndrome, and enhanced during pregnancy...
  11. Egi Y, Koyama S, Shioda T, Yamada K, Kawasaki T. Identification, purification and reconstitution of thiamin metabolizing enzymes in human red blood cells. Biochim Biophys Acta. 1992;1160:171-8 pubmed
    ..2 nmol/l of packed RBC, respectively, suggesting enzymatic conversion of thiamin to TDP and then to TTP. Thiamin pyrophosphokinase (TPK, EC 2.7.6...
  12. Schyns G, Potot S, Geng Y, Barbosa T, Henriques A, Perkins J. Isolation and characterization of new thiamine-deregulated mutants of Bacillus subtilis. J Bacteriol. 2005;187:8127-36 pubmed
    ..These results are consistent with the proposed "riboswitch" mechanism of thiamine gene regulation (W. C. Winkler, A. Nahvi, and R. R. Breaker, Nature 419:952-956, 2002). ..
  13. Fradin D, Bougneres P. Three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight. Ann Hum Genet. 2007;71:578-85 pubmed
    ..027). These observations suggest that genomic variations in the fetal and maternal TPK1 gene could contribute to the variability of birth weight in normal humans. ..
  14. Salem S, Zaki M, Bystroff C. Iterative non-sequential protein structural alignment. J Bioinform Comput Biol. 2009;7:571-96 pubmed
    ..Classification of folds using SNAP alignments was both highly sensitive and highly selective. The SNAP software along with the datasets are available online at ..
  15. Tokui M, Kubodera T, Gomi K, Yamashita N, Nishimura A. Construction of a thiamine pyrophosphate high-producing strain of Aspergillus oryzae by overexpression of three genes involved in thiamine biosynthesis. J Biosci Bioeng. 2011;111:388-90 pubmed publisher
    ..To improve the productivity of TPP in A. oryzae, we constructed the strain in which thiA, nmtA and thiP were overexpressed simultaneously. The resulting strain accumulated intracellular TPP 4-fold higher than did the control strain. ..
  16. Mayr J, Freisinger P, Schlachter K, Rolinski B, Zimmermann F, Scheffner T, et al. Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway. Am J Hum Genet. 2011;89:806-12 pubmed publisher
    ..A reduced concentration of TPP was found in the muscle and blood. Mutation analysis of TPK1 uncovered three missense, one splice-site, and one frameshift mutation resulting in decreased TPK protein levels. ..
  17. Matsuda T, Tonomura H, Baba A, Iwata H. Postnatal development of thiamine metabolism in rat skeletal muscle. Int J Biochem. 1991;23:203-6 pubmed
    ..3. Thiamine diphosphate level and the activity of 2-oxoglutarate dehydrogenase increased only in soleus muscle and thiamine triphosphate level increased only in extensor digitorum longus during development. ..
  18. Matsuda T, Doi T, Tonomura H, Baba A, Iwata H. Postnatal development of thiamine metabolism in rat brain. J Neurochem. 1989;52:842-6 pubmed
    ..It is concluded that thiamine metabolism in the brain changes during postnatal development in a different way from that in the liver and that the development of thiamine metabolism differs among brain regions. ..
  19. Laforenza U, Patrini C, Gastaldi G, Rindi G. Effects of acute and chronic ethanol administration on thiamine metabolizing enzymes in some brain areas and in other organs of the rat. Alcohol Alcohol. 1990;25:591-603 pubmed
    ..These changes may contribute to an important extent to the disturbances in thiamine cellular uptake and metabolism observed in alcoholism. ..
  20. Santini S, Monchois V, Mouz N, Sigoillot C, Rousselle T, Claverie J, et al. Structural characterization of CA1462, the Candida albicans thiamine pyrophosphokinase. BMC Struct Biol. 2008;8:33 pubmed publisher
    ..Finally, the TPK/Thiamine-PNP complex is consistent with a one step mechanism of pyrophosphorylation. ..
  21. Khan M, Ligon M, Hussey L, Hufnal B, Farber R, Munkácsy E, et al. TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging (Albany NY). 2013;5:741-58 pubmed
    ..Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension. ..
  22. Rindi G, Casirola D, Poggi V, De Vizia B, Patrini C, Laforenza U. Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia. J Inherit Metab Dis. 1992;15:231-42 pubmed
  23. Rindi G, Reggiani C, Patrini C, Gastaldi G, Laforenza U. Effect of ethanol on the in vivo kinetics of thiamine phosphorylation and dephosphorylation in different organs of rat--II. Acute effects. Alcohol Alcohol. 1992;27:505-22 pubmed
    ..T pyrophosphorylation was generally reduced, and T phosphates dephosphorylation generally enhanced. T became the most abundant component in the mixture released from all tissues. ..
  24. Müller I, Bergmann B, Groves M, Couto I, Amaral L, Begley T, et al. The vitamin B1 metabolism of Staphylococcus aureus is controlled at enzymatic and transcriptional levels. PLoS ONE. 2009;4:e7656 pubmed publisher
    ..aureus is strongly regulated at transcriptional as well as enzymatic levels. ..
  25. Paila U, Kondam R, Ranjan A. Genome bias influences amino acid choices: analysis of amino acid substitution and re-compilation of substitution matrices exclusive to an AT-biased genome. Nucleic Acids Res. 2008;36:6664-75 pubmed publisher
    ..This study has important implications on annotation of proteins that are of experimental interest but give poor sequence alignments with standard conventional matrices. ..
  26. Fitzsimons J, Vandenbyllaardt L, Brown S. The use of thiamine and thiamine antagonists to investigate the etiology of early mortality syndrome in lake trout (Salvelinus namaycush). Aquat Toxicol. 2001;52:229-39 pubmed
    ..These data provide experimental evidence supporting the hypothesis that a thiamine deficiency in the natural environment is the cause of EMS. ..
  27. Onozuka M, Konno H, Akaji K, Nishino H, Nosaka K. Molecular cloning and analysis of the 5'-flanking region of the human thiamin pyrophosphokinase gene. J Nutr Sci Vitaminol (Tokyo). 2005;51:274-7 pubmed
    We cloned and analyzed the 5'-flanking region of the human thiamin pyrophosphokinase gene (hTPK1)...
  28. Bettendorff L, Mastrogiacomo F, Kish S, Grisar T. Thiamine, thiamine phosphates, and their metabolizing enzymes in human brain. J Neurochem. 1996;66:250-8 pubmed
    ..These data, consistent with previous observations conducted in blood, suggest a tendency toward decreased thiamine status in older people. ..
  29. Mastrogiacoma F, Bettendorff L, Grisar T, Kish S. Brain thiamine, its phosphate esters, and its metabolizing enzymes in Alzheimer's disease. Ann Neurol. 1996;39:585-91 pubmed
  30. Gastaldi G, Casirola D, Patrini C, Ricci V, Laforenza U, Ferrari G, et al. Intestinal transport of thiamin and thiamin monophosphate in rat everted jejunal sacs: a comparative study using some potential inhibitors. Arch Int Physiol Biochim. 1988;96:223-30 pubmed
    ..In separate experiments, thiamin pyrophosphokinase (TPKase) and thiamin pyrophosphatase (TPPase) activities were determined in mucosal scrapings, with and ..
  31. Borgna Pignatti C, Marradi P, Pinelli L, Monetti N, Patrini C. Thiamine-responsive anemia in DIDMOAD syndrome. J Pediatr. 1989;114:405-10 pubmed
    ..We propose that an inherited abnormality of thiamine metabolism is responsible for the multisystem degenerative disorder known as DIDMOAD syndrome. ..
  32. Poggi V, Rindi G, Patrini C, De Vizia B, Longo G, Andria G. Studies on thiamine metabolism in thiamine-responsive megaloblastic anaemia. Eur J Pediatr. 1989;148:307-11 pubmed
    ..We propose that the disorder is caused by an inherited defect of thiamine transport, possibly related to deficient pyrophosphokinase activity, leading to intracellular depletion of active thiamine metabolite derivatives. ..
  33. Nishimura H, Kawasaki Y, Nosaka K, Kaneko Y, Iwashima A. A constitutive thiamine metabolism mutation, thi80, causing reduced thiamine pyrophosphokinase activity in Saccharomyces cerevisiae. J Bacteriol. 1991;173:2716-9 pubmed
    ..These results suggest that the utilization and synthesis of thiamine in Saccharomyces cerevisiae is controlled negatively by the intracellular thiamine pyrophosphate level. ..
  34. Toyoshima M, Oka A, Egi Y, Yamamoto T, Onozuka M, Nosaka K, et al. Thiamine-responsive congenital lactic acidosis: clinical and biochemical studies. Pediatr Neurol. 2005;33:98-104 pubmed
    ..Careful monitoring of lactate and pyruvate would be useful in determining thiamine dosage. ..
  35. Subramanian V, Subramanya S, Tsukamoto H, Said H. Effect of chronic alcohol feeding on physiological and molecular parameters of renal thiamin transport. Am J Physiol Renal Physiol. 2010;299:F28-34 pubmed publisher
    ..Chronic alcohol feeding also caused a significant reduction in the level of expression of thiamin pyrophosphokinase but not that of the mitochondrial thiamin pyrophosphate transporter...
  36. Grill J, Leblanc T, Baruchel A, Daniel M, Dresch C, Schaison G. Thiamine responsive anemia: report of a new case associated with a thiamine pyrophosphokinase deficiency. Nouv Rev Fr Hematol. 1991;33:543-4 pubmed
    ..Thus, etiology of the syndrome is not only a thiamine pyrophosphokinase deficiency as previously suggested. ..
  37. Iwashima A, Kinugasa A, Nose Y. Radiometric assay for thiamine pyrophosphokinase activity in human leukocytes. Acta Vitaminol Enzymol. 1983;5:41-5 pubmed
    ..2 +/- 6.6 p moles of thiamine pyrophosphate formed per mg protein per hour at 37 degrees C. No thiamine pyrophosphokinase activity was detected in hemolysate of human erythrocytes under the assay condition employed. ..
  38. Zastre J, Hanberry B, Sweet R, McGinnis A, Venuti K, Bartlett M, et al. Up-regulation of vitamin B1 homeostasis genes in breast cancer. J Nutr Biochem. 2013;24:1616-24 pubmed publisher
    ..Overall, these findings demonstrate an adaptive response by breast cancer cells to increase cellular availability of thiamine. ..
  39. Chan X, Wrenger C, Stahl K, Bergmann B, Winterberg M, Müller I, et al. Chemical and genetic validation of thiamine utilization as an antimalarial drug target. Nat Commun. 2013;4:2060 pubmed publisher
    ..Our studies therefore validate thiamine utilization as an antimalarial drug target and demonstrate that a single antimalarial can simultaneously target several enzymes located within distinct organelles. ..