Transketolase is an enzyme of both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis.

It catalyzes two important reactions, which operate in opposite directions in these two pathways.

First reaction

  1. In the first reaction of the non-oxidative "pentose phosphate pathway^:, the cofactor thiamine diphosphate accepts a 2-carbon fragment from a 5-carbon ketose (D-xylulose-5-P), then transfers this fragment to a 5-carbon aldose (D-ribose-5-P) to form a 7-carbon ketose (sedoheptulose-7-P). The abstraction of two carbons from D-xylulose-5-P yields the 3-carbon aldose glyceraldehyde-3-P.
  2. In the Calvin cycle, transketolase catalyzes the reverse reaction, the conversion of sedoheptulose-7-P and glyceraldehyde-3-P to pentoses, the aldose D-ribose-5-P and the ketose D-xylulose-5-P.

Second reaction

  1. The second reaction catalyzed by transketolase in the pentose phosphate pathway involves the same thiamine diphosphate-mediated transfer of a 2-carbon fragment from D-xylulose-5-P to the aldose erythrose-4-phosphate, affording fructose 6-phosphate and glyceraldehyde-3-P.
  2. Again, in the Calvin cycle exactly the same reaction occurs, but in the opposite direction. Moreover, in the Calvin cycle this is the first reaction catalyzed by transketolase, rather than the second.

In mammals, transketolase connects the pentose phosphate pathway to glycolysis, feeding excess sugar phosphates into the main carbohydrate metabolic pathways. Its presence is necessary for the production of NADPH, especially in tissues actively engaged in biosyntheses, such as fatty acid synthesis by the liver and mammary glands, and for steroid synthesis by the liver and adrenal glands.

Thiamine diphosphate is an essential cofactor, along with calcium.

Lack of Calcium should reduce Transketolase activity enhancing R5P synthesis and indirectly purine nucleotides with increased Uric Acid production


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When relevant for the function

  • Primary structure

  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage


mRNA synthesis
protein synthesis

post-translational modifications


cellular localization,
biological function

TKT activity regulates the ribose-5-phosphate (R5P) level, a substrate for synthesis of nucleotides and nucleic acids.

TKT low activity: high R5P + stoichiometric NADPH = high DNA synthesis

TKT high activity: low R5P + high NADPH = low DNA, high antioxidant activity (erythrocytes?)

TKT high activity: low R5P + high NADPH + higher ATP = low DNA, high fatty acids and cholesterol synthesis, high oxidative metabolism

Quertle: cell+cycle+TRANSKETOLASE

  • Enzymes
BRENDA - The Comprehensive Enzyme Information System"TKT":"TKTL1":
KEGG Pathways"TKT":"TKTL1":
Human Metabolome Database"TKT":"TKTL1":
  • Cell signaling and Ligand transport
  • Structural proteins



EDIM-TKTL1 blood test: a noninvasive method to detect upregulated glucose metabolism in patients with malignancies. 2012

To determine whether the TKTL1 protein epitope detection in monocytes (EDIM) test allows detection of upregulated glucose metabolism in malignancies.


The EDIM-TKTL1 blood test was conducted in 240 patients with 17 different confirmed or suspected malignancies. Test scores were compared with (18)F-fluoro-2-deoxy-D-glucose (FDG)-PET/computed tomography (CT) results.

EDIM-TKTL1 score and FDG-PET results showed a concordance of 90% with a sensitivity of 94% and specificity of 81%. Including CT data, all values were enhanced. A subgroup analysis of non-small-cell lung cancer patients showed a significant correlation between the EDIM-TKTL1 score and the primary tumor size determined by FDG-PET/CT.

EDIM-TKTL1 blood test revealed good concordance with FDG-PET/CT results in patients with malignancies demonstrating its efficacy to detect upregulation of glucose metabolism in primary tumors or metastases.

Mutations in the transketolase-like gene TKTL1: clinical implications for neurodegenerative diseases, diabetes and cancer. 2005

Transketolase proteins or transketolase enzyme activities have been related to neurodegenerative diseases, diabetes, and cancer. Transketolase enzyme variants and reduced transketolase enzyme activities are present in patients with the neurodegenerative disease Wernicke-Korsakoff syndrome. In Alzheimer's disease patients transketolase protein variants with different isoelectric points or a proteolytic cleavage leading to small transketolase protein isoforms have been identified. In diabetes mellitus patients reduced transketolase enzyme activities have been detected and the lipid-soluble thiamine derivative benfotiamine activates transketolase enzyme reactions, thereby blocking three major pathways of hyperglycemic damage and preventing diabetic retinopathy. In cancer inhibition of transketolase enzyme reactions suppresses tumor growth and metastasis. All the observed phenomena have been interpreted solely on the basis of a single transketolase gene (TKT) encoding a single transketolase enzyme. No mutations have been identified so far in TKT transketolase explaining the altered transketolase proteins or transketolase enzyme activities found in neurodegenerative diseases, diabetes and cancer. We demonstrate the presence of a second transketolase enzyme (TKTL1) in humans. During the evolution of the vertebrate genome, mutations in this transketolase gene (TKTL1) have led to tissue-specific transcripts different in size, which encode an enzymatically active transketolase protein as well as different smaller protein isoforms. The mutations within the TKTL1 gene caused a mutant transketolase enzyme with an altered substrate specificity and reaction modus. Here we characterize the TKTL1 gene and its encoded TKTL1 protein(s) and discuss the medical and clinical implications of this mutated transketolase. We furthermore postulate a novel metabolic concept for the understanding, prevention and therapy of neurodegenerative diseases, diabetes and cancer.


Le due isoforme non sono molto distanti (ca 20 proteine) ma potrebbero lo stesso avere effetti antagonistici

alcuni vicini di TKT aumentano il flusso glicolitico (meno R5P?)

From or to R5P??

Strategies for Wheat Stripe Rust Pathogenicity Identified by Transcriptome Sequencing, 2013

Stripe rust caused by the fungus Puccinia striiformis f.sp. tritici (Pst) is a major constraint to wheat production worldwide.

The molecular events that underlie Pst pathogenicity are largely unknown. Like all rusts, Pst creates a specialized cellular structure within host cells called the haustorium to obtain nutrients from wheat (analog to neurites?), and to secrete pathogenicity factors called effector proteins (neurotransmitters?). We purified Pst haustoria and used next-generation sequencing platforms to assemble the haustorial transcriptome as well as the transcriptome of germinated spores. 12,282 transcripts were assembled from 454-pyrosequencing data and used as reference for digital gene expression analysis to compare the germinated uredinospores and haustoria transcriptomes based on Illumina RNAseq data. More than 400 genes encoding secreted proteins which constitute candidate effectors were identified from the haustorial transcriptome, with two thirds of these up-regulated in this tissue compared to germinated spores. RT-PCR analysis confirmed the expression patterns of 94 effector candidates. The analysis also revealed that spores rely mainly on stored energy reserves for growth and development (like glicogen, casein, ferritin for eukaryota?), while haustoria take up host nutrients for massive energy production for biosynthetic pathways and the ultimate production of spores. Together, these studies substantially increase our knowledge of potential Pst effectors and provide new insights into the pathogenic strategies of this important organism.

Similarity with Plasmodium and/or neuron

The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. 2001

Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, approximately 2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study.

[Tumor and body interrelationships in 14C-thiamine utilization].1979

Variations in the content of 14C-thiamine, thiamine-dependent enzyme transketolase (TK), and thiamine diphosphate (TDP) in mouse tissues were studied during Ehrlich's ascites tumour growth. The concentration of TDP in the liver of tumour-bearing animals continuously drops during 10 days after inoculation, TDP level in the tumour itself decreases more abruptly by the terminal period of tumour growth (the 10th day). At the same time the tumour demonstrates sharp deficiency of the coenzyme and redundance of apoenzymatic forms of TK. The growing deficiency of thiamine in the tumour favours greater tension of thiamine metabolism and appearance of competitive tumour-host interrelationships that are most pronounced in the presence of hypovitaminosis.

Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2-13C2]gluco, 1998, fulltext

Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2-13C2]gluco, 1998

Papers citing Mass isotopomer study of the nonoxidative pathways of the pentose cycle with [1,2-13C2]gluco, 1998

Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis. 2013

The mechanisms by which deregulated nuclear factor erythroid-2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and ¹³C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, reprogramming glucose metabolism. Sustained activation of NRF2 signaling in cancer cells attenuated miR-1 and miR-206 expression, leading to enhanced expression of PPP genes. Conversely, overexpression of miR-1 and miR-206 decreased the expression of metabolic genes and dramatically impaired NADPH production, ribose synthesis, and in vivo tumor growth in mice. Loss of NRF2 decreased the expression of the redox-sensitive histone deacetylase, HDAC4, resulting in increased expression of miR-1 and miR-206, and not only inhibiting PPP expression and activity but functioning as a regulatory feedback loop that repressed HDAC4 expression. In primary tumor samples, the expression of miR-1 and miR-206 was inversely correlated with PPP gene expression, and increased expression of NRF2-dependent genes was associated with poor prognosis. Our results demonstrate that microRNA-dependent (miRNA-dependent) regulation of the PPP via NRF2 and HDAC4 represents a novel link between miRNA regulation, glucose metabolism, and ROS homeostasis in cancer cells.

Central carbon metabolism in the progression of mammary carcinoma. 2008

There is a growing belief that the metabolic program of breast tumor cells could be a therapeutic target. Yet, without detailed information on central carbon metabolism in breast tumors it is impossible to know which metabolic pathways to target, and how their inhibition might influence different stages of breast tumor progression. Here we perform the first comprehensive profiling of central metabolism in the MCF10 model of mammary carcinoma, where the steps of breast tumor progression (transformation, tumorigenicity and metastasis) can all be examined in the context of the same genetic background. The metabolism of [U-(13)C]-glucose by a series of progressively more aggressive MCF10 cell lines was tracked by 2D NMR and mass spectrometry. From this analysis the flux of carbon through distinct metabolic reactions was quantified by isotopomer modeling. The results indicate widespread changes to central metabolism upon cellular transformation including increased carbon flux through the pentose phosphate pathway (PPP), the TCA cycle, as well as increased synthesis of glutamate, glutathione and fatty acids (including elongation and desaturation). The de novo synthesis of glycine increased upon transformation as well as at each subsequent step of breast tumor cell progression. Interestingly, the major metabolic shift in metastatic cells is a large increase in the de novo synthesis of proline. This work provides the first comprehensive view of changes to central metabolism as a result of breast tumor progression.

2014-01-17T09:40:07 - Gianpiero Pescarmona

Thiamine and Hashimoto's Thyroiditis: A Report of Three Cases. 2013
J Altern Complement Med.

Abstract Objectives: In a previous study on fatigue and related disorders in inflammatory bowel disease (IBD), we observed that IBD patients improved after treatment with high-dose thiamine. We hypothesized that the chronic fatigue accompanying inflammatory and autoimmune diseases is the clinical manifestation of a mild thiamine deficiency that is probably due to a dysfunction of the intracellular transport or to enzymatic abnormalities. Hashimoto's thyroiditis is both a common automimmune disease and cause of hypothyroidism. Although levothyroxine, a thyroid hormone, is the treatment of choice for hypothyroidism, a significant number of patients on thyroid hormone replacement therapy report not feeling well despite having thyroid function tests within the healthy range. Based on our hypothesis, we started treating the fatigue in patients affected by Hashimoto's thyroiditis and taking a thyroid hormone with thiamine. This is a report of the outcomes of three cases in which the fatigue component reported by patients with Hashimoto's thyroiditis was treated with thiamine. Design: Three patients on thyroid hormone replacement because of Hashimoto's thyroiditis were treated for the fatigue component of the disease from May to July 2011. Fatigue was measured using the Fatigue Severity Scale. Free thiamine in the serum and thiamine pyrophosphate in red cells were tested before and after the therapy. All three patients received oral (600 mg/day) or parenteral (100 mg/ml every four days) doses of thiamine. Results: Treatment with thiamine led to partial or complete regression of the fatigue within a few hours or days. Conclusion: As the administration of thiamine led to a partial or complete regression of the fatigue and related disorders, it is reasonable to infer that the administration of large quantities of thiamine restores thiamine-dependent processes. The mild thiamine deficiency suggested by fatigue and related disorders may be due a dysfunction of the intracellular transport of thiamine or to enzymatic abnormalities most likely related to the autoimmune process of the disease.

Pala MI

600 mg/day Thiamine relieves fatigue

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