Preparative scale enzymatic synthesis of d-sedoheptulose-7-phosphate from β-hydroxypyruvate and d-ribose-5-phosphate

Charmantray, Franck; Hélaine, Virgil; Légeret, Bertrand; Hecquet, Laurence

doi:10.1016/j.molcatb.2008.06.005

Cited by 49 publications

(31 citation statements)

References 24 publications

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“…The 1 H-NMR spectrum shows that the β-furanose form of sedoheptulose had the highest concentration of the four anomeric forms. This is in line with observations on the anomeric forms of sedoheptulose-7-phosphate (α-furanose/β-furanose/α-pyranose= 20%:60%:20%) [15,16]. As indicated in Fig.…”

Section: Resultssupporting

confidence: 92%

“…1A). Resonance assignments were based on previously reported NMR spectra of sedoheptulose (The Human Metabolome Database (HMDB, http://www.hmdb.ca), HMDB ID 03219) and sedoheptulose-7-phosphate [15] and simulated NMR spectra of four sedoheptulose anomers: α -furanose, β-furanose, α-pyranose, and β-pyranose (ACD/HNMR Predictor, Advanced Chemistry Development, Toronto, Ontario, Canada). The 1 H-NMR spectrum shows that the β-furanose form of sedoheptulose had the highest concentration of the four anomeric forms.…”

Section: Resultsmentioning

confidence: 99%

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Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency

Engelke

Zijlstra

Mochel

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Background Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency. Method Urine from 6 TALDO-deficient patients and TALDO-deficient knock-out mice were analyzed using 1H-NMR spectroscopy and GC–mass spectrometry. Results Our data confirm the known metabolic characteristics in TALDO-deficient patients. The β-furanose form was the major sedoheptulose anomer in TALDO-deficient patients. Erythronic acid was identified as a major abnormal metabolite in all patients and in knock-out TALDO mice implicating an as yet unknown biochemical pathway in this disease. A putative sequence of enzymatic reactions leading to the formation of erythronic acid is presented. The urinary concentration of the citric acid cycle intermediates 2-oxoglutaric acid and fumaric acid was increased in the majority of TALDO-deficient patients but not in the knock-out mice. Conclusion Erythronic acid is a novel and major hallmark in TALDO deficiency. The pathway leading to its production may play a role in healthy humans as well. In TALDO-deficient patients, there is an increased flux through this pathway. The finding of increased citric acid cycle intermediates hints toward a disturbed mitochondrial metabolism in TALDO deficiency.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency

Engelke

Zijlstra

Mochel

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Chemoenzymatic Synthesis of S7P-The donor sugar S7P was chemoenzymatically synthesized, relying on the protocol given by Charmantray et al (30) but using wild-type TKT from E. coli. In brief, TKT was reacted with artificial donor ␤-hydroxypyruvate and the physiological acceptor R5P, making the donor halfreaction irreversible.…”

Section: Methodsmentioning

confidence: 99%

The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action

Mitschke

Parthier

Schröder-Tittmann

et al. 2010

Journal of Biological Chemistry

169

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The crystal structure of human transketolase (TKT), a thiamine diphosphate (ThDP) and Ca 2؉ -dependent enzyme that catalyzes the interketol transfer between ketoses and aldoses as part of the pentose phosphate pathway, has been determined to 1.75 Å resolution. The recombinantly produced protein crystallized in space group C2 containing one monomer in the asymmetric unit. Two monomers form the homodimeric biological assembly with two identical active sites at the dimer interface. Transketolase (TKT 3 ; EC 2.2.1.1) is a ubiquitous enzyme in cellular carbon metabolism and requires thiamine diphosphate (ThDP), the biologically active derivative of vitamin B1, and Ca 2ϩ ions as cofactors for enzymatic activity (1, 2). TKT catalyzes the reversible transfer of two-carbon (1,2-dihydroxyethyl) units from ketose phosphates to the C1 position of aldose phosphates and thus provides, together with the Schiff base-forming transaldolase, a reversible link between glycolysis and the pentose phosphate pathway. This shunt permits cells a flexible adaptation to different metabolic needs as the pentose phosphate pathway supplies intermediates for other metabolic pathways; generates precursors for biosynthesis of nucleotides, aromatic amino acids, and vitamins; and further produces NADPH for sustaining the glutathione level and for reductive biosynthetic pathways of, for example, cholesterol and fatty acids.TKT acts on different ketose phosphate (donor) and aldose phosphate (acceptor) substrates of variable carbon chain length (3-7 carbons) in two major, essentially reversible reactions. REACTIONS 1 AND 2A simplified reaction scheme for the TKT-catalyzed conversion of substrates X5P and R5P into products S7P and G3P is shown in Fig. 1. The reaction cycle can be subdivided into a donor half-reaction (donor ligation and cleavage) and an acceptor half-reaction (acceptor ligation and product liberation) (3).After formation of the reactive ylide form of ThDP, the C2 carbanion of ThDP attacks the carbonyl of donor X5P in a nucleophilic manner to yield the covalent donor-ThDP adduct X5P-ThDP (step 1). Ionization of C3-OH and cleavage of the scissile C2-C3 bond of X5P-ThDP results in the formation of product G3P and of the 1,2-dihydroxylethyl-ThDP (DHEThDP) carbanion/enamine intermediate (step 2). This intermediate may then react with either G3P (reverse reaction of step 2) or R5P in competing equilibria. In the latter case, C2␣ of DHE-ThDP ligates to C1 of R5P (in the acyclic form), yielding * This work was supported by a grant from the "Fonds der Chemischen Industrie" (stipend to S. L.) and the Deutsche Forschungsgemeinschaft-funded Gö ttingen Graduate School for Neurosciences and Molecular Biosciences (to K. T.

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“…TK was purified from the crude extract (Charmantray et al, 2009). Typically, 50 mg of proteins from the crude extract was stirred at 4 • C for 2 h with 10 mL of Q-sepharose resin, previously rinsed in 100 mM Tris buffer pH 7.4.…”

Section: Expression and Purification Of Transketolasementioning

confidence: 99%

Fluorogenic substrates for the screening assay of transketolase through beta-elimination of umbelliferone—Development, scope and limitations

Charmantray

Légeret

Hélaine

et al. 2010

Journal of Biotechnology

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Preparative scale enzymatic synthesis of d-sedoheptulose-7-phosphate from β-hydroxypyruvate and d-ribose-5-phosphate

Cited by 49 publications

References 24 publications

Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency

Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency

The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action

Fluorogenic substrates for the screening assay of transketolase through beta-elimination of umbelliferone—Development, scope and limitations

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