Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2009 Mar 24;25(2):94–99. doi: 10.1007/s12264-009-1113-y

A review on research progress of transketolase

转酮醇酶的研究进展

Jing Zhao 1, Chun-Jiu Zhong 1,2,✉
PMCID: PMC5552578  PMID: 19290028

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.

Keywords: Transketolase, Pentose phosphate pathway, neurodegenerative disease, TKTL-1 gene

References

  • [1].Horecker B.L. The pentose phosphate pathway. J Biol Chem. 2002;277:47965–47971. doi: 10.1074/jbc.X200007200. [DOI] [PubMed] [Google Scholar]
  • [2].Blass J.P., Gibson G.E. Abnormality of a thiamine-requiring enzyme in patients with Wernicke-Korsakoff syndrome. New Engl J Med. 1977;297:1367–1370. doi: 10.1056/NEJM197712222972503. [DOI] [PubMed] [Google Scholar]
  • [3].Gibson G.E., Sheu K.F.R., Baker A.C., Carlson K.C., Harding B., Perrino P., Blass J.P. Reduced activities of thiamine-dependent enzymes in brains and peripheral tissues of Alzheimer’s patients. Arch Neurol. 1988;45:836–840. doi: 10.1001/archneur.1988.00520320022009. [DOI] [PubMed] [Google Scholar]
  • [4].Hammes H.P., 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. doi: 10.1038/nm834. [DOI] [PubMed] [Google Scholar]
  • [5].Boros L.G., Puigjaner J., Cascante M., Lee W.-N., Brandes J.L., Bassilian S., et al. Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. Cancer Res. 1997;57:4242–4248. [PubMed] [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. doi: 10.1002/j.1460-2075.1992.tb05301.x. [DOI] [PMC free article] [PubMed] [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. doi: 10.1016/0167-4838(86)90143-3. [DOI] [PubMed] [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. doi: 10.1006/jmbi.1994.1299. [DOI] [PubMed] [Google Scholar]
  • [9].Usmanov R.A., Kochetov G.A. Study of different conformational states of transketolase by the method of perturbation UV-spectrophotometry. Biokhimiia. 1978;43:1796–1804. [PubMed] [Google Scholar]
  • [10].Sundström M., Lindqvist Y., Schneider G. Three-dimensional structure of apotransketolase. FEBS Lett. 1992;313:229–231. doi: 10.1016/0014-5793(92)81197-T. [DOI] [PubMed] [Google Scholar]
  • [11].Schenk G., Duggleby R.G., Nixon P.F. Properties and functions of the thiamin diphosphate dependent enzyme transketolase. Inter J Biochem Cell Biol. 1998;30:1297–1318. doi: 10.1016/S1357-2725(98)00095-8. [DOI] [PubMed] [Google Scholar]
  • [12].Esakova O.A., Meshalkina L.E., Golbik R., Hübner G., Kochetov G.A. Donor substrate regulation of transketolase. Eur J Biochem. 2004;271(21):4189–4194. doi: 10.1111/j.1432-1033.2004.04357.x. [DOI] [PubMed] [Google Scholar]
  • [13].Booth C.K., Nixon P.F. Reconstitution of holotransketolase is by a thiamin-diphosphate-magnesium complex. Eur J Biochem. 1993;218(1):261–265. doi: 10.1111/j.1432-1033.1993.tb18373.x. [DOI] [PubMed] [Google Scholar]
  • [14].Masri S.W., Ali M., Gubler C.J. 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. doi: 10.1016/0305-0491(88)90056-9. [DOI] [PubMed] [Google Scholar]
  • [15].Williams J.F., Arora K.K., Longenecker J.P. 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. doi: 10.1016/0020-711X(87)90239-4. [DOI] [PubMed] [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. doi: 10.1021/bi00859a046. [DOI] [PubMed] [Google Scholar]
  • [17].Kiely M.E., Tan E.L., Wood T. The purification of transketolase from Candida utilis. Can J Biochem. 1969;47:455–460. doi: 10.1139/o69-071. [DOI] [PubMed] [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. doi: 10.1016/0167-4838(86)90143-3. [DOI] [PubMed] [Google Scholar]
  • [19].Coy J.F., 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. doi: 10.1006/geno.1996.0124. [DOI] [PubMed] [Google Scholar]
  • [20].Glinsky G.V., Krones-Herzig A., Glinskii A.B. 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. doi: 10.1016/S1476-5586(03)80054-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Butterworth R.F., Gaudreau C., Vincelette J., Bourgault A.M., Lamothe F., Nutini A.M. Thiamine deficiency and Wernicke’s encephalopathy in AIDS. Metab Brain Dis. 1991;6:207–212. doi: 10.1007/BF00996920. [DOI] [PubMed] [Google Scholar]
  • [22].Kovina M.V., Selivanov V.A., Kochevova N.V., Kochetov G.A. Kinetic mechanism of active site non-equivalence in transketolase. FEBS Lett. 1991;418:11–14. doi: 10.1016/S0014-5793(97)01331-8. [DOI] [PubMed] [Google Scholar]
  • [23].Victor M., Adams R.D., Collins G.H. 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] [Google Scholar]
  • [24].Thomson A.D., Cook C.C., Touquet R., Henry J.A. 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. doi: 10.1093/alcalc/37.6.513. [DOI] [PubMed] [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. doi: 10.1007/BF01991863. [DOI] [PubMed] [Google Scholar]
  • [26].Hazell A.S., Rao K.V., Danbolt N.C., Pow D.V., Butterworth R.F. 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. doi: 10.1046/j.1471-4159.2001.00436.x. [DOI] [PubMed] [Google Scholar]
  • [27].Langlais P.J., Mair R.G. 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. doi: 10.1523/JNEUROSCI.10-05-01664.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Calingasan N.Y., Gandy S.E., Baker H., Sheu K.F., Kim K.S., Wisniewski H.M., et al. Accumulation of amyloid precusor protein-like immunoreactivity in rat brain in response to thiamine deficiency. Brain Res. 1995;677:50–60. doi: 10.1016/0006-8993(95)00136-E. [DOI] [PubMed] [Google Scholar]
  • [29].Langlais P.J., Anderson G., Guo S.X., Bondy S.C. Increased cerebral free radical production during thiamine deficiency. Metab Brain Dis. 1997;12:137–143. [PubMed] [Google Scholar]
  • [30].Todd K.G., Butterworth R.F. Early microglial response in experimental thiamine deficiency: an immunohistochemical analysis. Glia. 1999;25:190–198. doi: 10.1002/(SICI)1098-1136(19990115)25:2<190::AID-GLIA9>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]
  • [31].Calingasan N.Y., Park L.C., Calo L.L., Trifiletti R.R., Gandy S.E., Gibson G.E. 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. doi: 10.1016/S0002-9440(10)65602-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Desjardins P., Butterworth R.F. 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. doi: 10.1016/0006-291X(90)90686-H. [DOI] [PubMed] [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. doi: 10.1016/0022-510X(91)90147-Y. [DOI] [PubMed] [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. doi: 10.1002/(SICI)1097-4652(199707)172:1<63::AID-JCP7>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]
  • [36].Brownlee M., Vlassara H., Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med. 1984;101:527–537. doi: 10.7326/0003-4819-101-4-527. [DOI] [PubMed] [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 J.H., Guo C.K., Cai P.C. Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells. Cancer Lett. 2007;253(1):108–114. doi: 10.1016/j.canlet.2007.01.010. [DOI] [PubMed] [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. doi: 10.1038/sj.bjc.6602962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Gatenby R.A., Gillies R.J. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4:891–899. doi: 10.1038/nrc1478. [DOI] [PubMed] [Google Scholar]
  • [41].Rais B., Comin B., Puigjaner J., Brandes J.L., 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. doi: 10.1016/S0014-5793(99)00924-2. [DOI] [PubMed] [Google Scholar]
  • [42].Boros L.G., Brandes J.L., Lee W.N., Cascante M., Puigjaner J., Revesz E., et al. Thiamine supplementation to cancer patients: a doubleedged sword. Anticancer Res. 1998;18:595–602. [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES