Skip to main content

Advertisement

Log in

A review on research progress of transketolase

转酮醇酶的研究进展

  • Minireview
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, catalyzes several key reactions of nonoxidative branch of pentose phosphate pathway. TK is a homodimer with two active sites that locate at the interface between the contacting monomers. Both ThDP and bivalent cations are strictly needed for TK activation, just like that for all ThDP-dependent enzymes. TK exists in all organisms that have been investigated. Up to now, one TK gene (TKT) and two transketolase-like genes (TKTL1 and TKTL2) have been identified in human genome. TKTL1 is reported to play a pivotal role in carcinogenesis and may have important implications in the nutrition and future treatment of patients with cancer. Researchers have found TK variants and reduced activities of TK enzyme in patients with neurodegenerative diseases, diabetes, and cancer. Recent studies indicated TK as a novel role in the prevention and therapy of these diseases.

摘要

转酮醇酶 (Transketolase, TK) 是一种焦磷酸硫胺素 (thiamine diphosphate, ThDP) 依赖性酶, 负责催化磷酸戊糖通路中碳水化合物转化的一个关键反应。 此酶属于同源二聚体, 在单体间的接触界面上存在两个活性部位。 与所有的焦磷酸硫胺素依赖性酶一样, TK 活性不仅依赖于焦磷酸硫胺素的存在, 还需要二价阳离子。 TK 存在于所有研究过的生物体中。 迄今为止, 在人类基因组中, 已经确定了一个 TK 基因和两个 TK 相似基因, 即转酮醇酶基因 (TKT)、 转酮醇酶样基因-1 (transketolase like-1, TKTL-1) 和转酮醇酶样基因-2 (transketolase like-2, TKTL-2)。 据报道, TKTL-1 在肿瘤发生中起着重要的作用, 同时对肿瘤患者的营养搭配及未来的治疗等方面有着重要的提示。 在神经变性疾病、 糖尿病和癌症中均发现转酮醇酶样基因变异体的存在, 转酮醇酶的活性也有所降低。 这些资料为更好地研究这些疾病的发病机理提供了新的线索, 并有助于建立新的预防和治疗手段。

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Horecker BL. The pentose phosphate pathway. J Biol Chem 2002, 277: 47965–47971.

    Article  PubMed  CAS  Google Scholar 

  2. Blass JP, Gibson GE. Abnormality of a thiamine-requiring enzyme in patients with Wernicke-Korsakoff syndrome. New Engl J Med 1977, 297: 1367–1370.

    PubMed  CAS  Google Scholar 

  3. Gibson GE, Sheu KFR, Baker AC, Carlson KC, Harding B, Perrino P, Blass JP. Reduced activities of thiamine-dependent enzymes in brains and peripheral tissues of Alzheimer’s patients. Arch Neurol 1988, 45: 836–840.

    PubMed  CAS  Google Scholar 

  4. Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 2003, 9: 294–99.

    Article  PubMed  CAS  Google Scholar 

  5. Boros LG, Puigjaner J, Cascante M, Lee W-NP, Brandes JL, Bassilian S, et al. Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. Cancer Res 1997, 57: 4242–4248.

    PubMed  CAS  Google Scholar 

  6. Lindqvist Y, Schneider G, Ermler U, Sundstrfim M. Threedimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5A° resolution. EMBO J 1992, 11: 2373–2379.

    PubMed  CAS  Google Scholar 

  7. Takeuchi T, Nishino K, Itokawa Y. Purification and characterisation of and preparation of an antibody to transketolase from human red blood cells. Biochem Biophys Acta 1986, 872: 24–32.

    PubMed  CAS  Google Scholar 

  8. Nikkola M, Lindqvist Y, Schneider G. Refined structure of transketolase from Saccharomyces cerevisiae at 2.0 A° resolution, J Mol Biol 1994, 238: 387–404.

    Article  PubMed  CAS  Google Scholar 

  9. Usmanov RA, Kochetov GA. Study of different conformational states of transketolase by the method of perturbation UV-spectrophotometry. Biokhimiia 1978, 43:1796–1804 (in Russian).

    PubMed  CAS  Google Scholar 

  10. Sundström M, Lindqvist Y, Schneider G. Three-dimensional structure of apotransketolase. FEBS Lett 1992, 313: 229–231.

    Article  PubMed  Google Scholar 

  11. Schenk G, Duggleby RG, Nixon PF. Properties and functions of the thiamin diphosphate dependent enzyme transketolase. Inter J Biochem Cell Biol 1998, 30: 1297–1318.

    Article  CAS  Google Scholar 

  12. Esakova OA, Meshalkina LE, Golbik R, Hübner G, Kochetov GA. Donor substrate regulation of transketolase. Eur J Biochem 2004, 271(21): 4189–4194.

    Article  PubMed  CAS  Google Scholar 

  13. Booth CK, Nixon PF. Reconstitution of holotransketolase is by a thiamin-diphosphate-magnesium complex. Eur J Biochem 1993, 218(1): 261–265.

    Article  PubMed  CAS  Google Scholar 

  14. Masri SW, Ali M, Gubler CJ. Isolation of transketolase from rabbit liver and comparison of some of its kinetic properties with transketolase from other sources. Comp Biochem Physiol 1988, 90B: 167–172.

    CAS  Google Scholar 

  15. Williams JF, Arora KK, Longenecker JP. The pentose pathway: a random harvest. Impediments which oppose acceptance of the classical (F-type) pentose cycle for liver, some neoplasms and photosynthetic tissue. The case for the L-type pentose pathway. Int J Biochem 1987, 19: 749–817.

    Article  PubMed  CAS  Google Scholar 

  16. Katz J, Rognstad R. The labeling of pentose phosphate from glucose-14C and estimation of the rates of transaldolase, transketolase, the contribution of the pentose cycle, and ribose phosphate synthesis. Biochemistry 1967, 6: 2227–2247.

    Article  PubMed  CAS  Google Scholar 

  17. Kiely ME, Tan EL, Wood T. The purification of transketolase from Candida utilis. Can J Biochem 1969, 47: 455–460.

    Article  PubMed  CAS  Google Scholar 

  18. Takeuchi T, Nishino K, Itokawa Y. Purification and characterisation of, and preparation of an antibody to, transketolase from human red blood cells. Biochem Biophys Acta 1986, 872: 24–32.

    PubMed  CAS  Google Scholar 

  19. Coy JF, Dübel S, Kioschis P, Thomas K, Micklem G, Delius H, et al. Molecular cloning of tissue-specific transcripts of a transketolaserelated gene: implications for the evolution of new vertebrate genes. Genomics 1996, 32: 309–316.

    Article  PubMed  CAS  Google Scholar 

  20. Glinsky GV, Krones-Herzig A, Glinskii AB. Malignancy-associated regions of transcriptional activation: gene expression profiling identifies common chromosomal regions of a recurrent transcriptional activation in human prostate, breast, ovarian, and colon cancers. Neoplasia 2003, 5: 218–228.

    PubMed  CAS  Google Scholar 

  21. Butterworth RF, Gaudreau C, Vincelette J, Bourgault AM, Lamothe F, Nutini AM. Thiamine deficiency and Wernicke’s encephalopathy in AIDS. Metab Brain Dis 1991, 6: 207–212.

    Article  PubMed  CAS  Google Scholar 

  22. Kovina MV, Selivanov VA, Kochevova NV, Kochetov GA. Kinetic mechanism of active site non-equivalence in transketolase. FEBS Lett 1991, 418: 11–14.

    Article  Google Scholar 

  23. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff syndrome: A clinical and pathological study of 245 patients, 82 with post-mortem examinations. Contemp Neurol Ser 1971, 7: 1–206.

    PubMed  CAS  Google Scholar 

  24. Thomson AD, Cook CC, Touquet R, Henry JA. Royal College of Physicians, London. The Royal College of Physicians Report on Alcohol: Guidelines for managing Wernicke’s encephalopathy in the Accident and Emergency Department. Alcohol Alcohol 2002, 37(6): 513–521.

    PubMed  CAS  Google Scholar 

  25. Harata N, Iwasaki Y. Evidence for early blood-brain barrier breakdown in experimental deficiency in the mouse. Metabolic Brain Disorder 1995, 10: 159–174.

    Article  CAS  Google Scholar 

  26. Hazell AS, Rao KV, Danbolt NC, Pow DV, Butterworth RF. Selective down-regulation of the astrocyte glutamate transporters GLT1 and GLAST within the medial thalamus in experimental Wernicke’s encephalopathy. J Neurochem 2001, 78: 560–568.

    Article  PubMed  CAS  Google Scholar 

  27. Langlais PJ, Mair RG. Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain. J Neurosci 1990, 10: 1664–1674.

    PubMed  CAS  Google Scholar 

  28. Calingasan NY, Gandy SE, Baker H, Sheu KF, Kim KS, Wisniewski HM, et al. Accumulation of amyloid precusor protein-like immunoreactivity in rat brain in response to thiamine deficiency. Brain Res 1995, 677: 50–60.

    Article  PubMed  CAS  Google Scholar 

  29. Langlais PJ, Anderson G, Guo SX. Bondy SC. Increased cerebral free radical production during thiamine deficiency. Metab Brain Dis 1997, 12: 137–143.

    PubMed  CAS  Google Scholar 

  30. Todd KG, Butterworth RF. Early microglial response in experimental thiamine deficiency: an immunohistochemical analysis. Glia 1999, 25: 190–198.

    Article  PubMed  CAS  Google Scholar 

  31. Calingasan NY, Park LC, Calo LL. Trifiletti RR, Gandy SE, Gibson GE. Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism. Am J Pathol 1998, 153: 599–610.

    PubMed  CAS  Google Scholar 

  32. Desjardins P, Butterworth RF. Pathogenesis of selective neuronal loss in Wernicke-Korsakoff Syndrome: role of oxidative stress. New York: Marcel Dekker, 2003, pp 339–347.

    Google Scholar 

  33. Paoletti F, Mocali A, Marchi M, Sorbi S, Piacentini S. Occurrence of transketolase abnormalities in extracts offoreskin fibroblasts from patients with Alzheimer’s disease. Biochem Biophys Res Commun 1990, 172: 396–401.

    Article  PubMed  CAS  Google Scholar 

  34. Paoletti F, Mocali A. Enhanced proteolytic activities in cultured fibroblasts of Alzheimer patients are revealed by peculiar transketolase alterations. J Neurol Sci 1991, 105: 211–216.

    Article  PubMed  CAS  Google Scholar 

  35. Paoletti F, Mocali A, Tombaccini D. Cysteine proteinases are responsible for characteristic transketolase alterations in Alzheimer fibroblasts. J Cell Physiol 1997, 172: 63–68.

    Article  PubMed  CAS  Google Scholar 

  36. Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med 1984, 101: 527–537.

    PubMed  CAS  Google Scholar 

  37. Cascante M, Comin B, Raïs B, Boren J, Centelles JJ. Application of metabolic control analysis to the design of a new strategy for cancer therapy. The Netherlands: Kluwer Academic 2000, pp 173–180.

  38. Zhang S, Yang JH, Guo CK, Cai PC. Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells. Cancer Lett 2007, 253(1): 108–114.

    Article  PubMed  CAS  Google Scholar 

  39. Langbein S, Zerilli M, Hausen A, Staiger W, Rensch-Boschert K, Lukan N. Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. British Journal of Cancer 2006, 94: 578–585.

    Article  PubMed  CAS  Google Scholar 

  40. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004, 4: 891–899.

    Article  PubMed  CAS  Google Scholar 

  41. Rais B, Comin B, Puigjaner J, Brandes JL, Creppy E, Saboureau D et al. Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich’s tumor cells through inhibition of the pentose cycle. FEBS Lett 1999, 456: 113–18.

    Article  PubMed  CAS  Google Scholar 

  42. Boros LG, Brandes JL, Lee WN, Cascante M, Puigjaner J, Revesz E, et al. Thiamine supplementation to cancer patients: a doubleedged sword. Anticancer Res 1998, 18: 595–602.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chun-Jiu Zhong  (钟春玖).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, J., Zhong, CJ. A review on research progress of transketolase. Neurosci. Bull. 25, 94–99 (2009). https://doi.org/10.1007/s12264-009-1113-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-009-1113-y

Keywords

关键词

CLC number

Navigation