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

U. F H Engelke, F. S M Zijlstra, Fanny Mochel, Vassili Valayannopoulos, Daniel Rabier, L. A J Kluijtmans, András Perl, Nanda M. Verhoeven-Duif, Pascale de Lonlay, M. M C Wamelink, Cornelis Jakobs, Eva Morava-Kozicz, Ron A. Wevers

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1028-1035
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1802
Issue number11
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

Biomarkers
Knockout Mice
Citric Acid Cycle
Ribitol
Erythritol
erythronic acid
Transaldolase Deficiency
Mass Spectrometry
Magnetic Resonance Spectroscopy
Urine
sedoheptulose

Keywords

  • 2-Oxoglutaric acid
  • Citric acid cycle intermediates
  • Erythronic acid
  • NMR spectroscopy
  • Pentose phosphate pathway
  • Polyols
  • Sedoheptulose
  • Transaldolase deficiency

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Engelke, U. F. H., Zijlstra, F. S. M., Mochel, F., Valayannopoulos, V., Rabier, D., Kluijtmans, L. A. J., ... Wevers, R. A. (2010). Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1802(11), 1028-1035. https://doi.org/10.1016/j.bbadis.2010.06.007

Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency. / Engelke, U. F H; Zijlstra, F. S M; Mochel, Fanny; Valayannopoulos, Vassili; Rabier, Daniel; Kluijtmans, L. A J; Perl, András; Verhoeven-Duif, Nanda M.; de Lonlay, Pascale; Wamelink, M. M C; Jakobs, Cornelis; Morava-Kozicz, Eva; Wevers, Ron A.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1802, No. 11, 01.11.2010, p. 1028-1035.

Research output: Contribution to journalArticle

Engelke, UFH, Zijlstra, FSM, Mochel, F, Valayannopoulos, V, Rabier, D, Kluijtmans, LAJ, Perl, A, Verhoeven-Duif, NM, de Lonlay, P, Wamelink, MMC, Jakobs, C, Morava-Kozicz, E & Wevers, RA 2010, 'Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1802, no. 11, pp. 1028-1035. https://doi.org/10.1016/j.bbadis.2010.06.007
Engelke, U. F H ; Zijlstra, F. S M ; Mochel, Fanny ; Valayannopoulos, Vassili ; Rabier, Daniel ; Kluijtmans, L. A J ; Perl, András ; Verhoeven-Duif, Nanda M. ; de Lonlay, Pascale ; Wamelink, M. M C ; Jakobs, Cornelis ; Morava-Kozicz, Eva ; Wevers, Ron A. / Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2010 ; Vol. 1802, No. 11. pp. 1028-1035.
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AU - Engelke, U. F H

AU - Zijlstra, F. S M

AU - Mochel, Fanny

AU - Valayannopoulos, Vassili

AU - Rabier, Daniel

AU - Kluijtmans, L. A J

AU - Perl, András

AU - Verhoeven-Duif, Nanda M.

AU - de Lonlay, Pascale

AU - Wamelink, M. M C

AU - Jakobs, Cornelis

AU - Morava-Kozicz, Eva

AU - Wevers, Ron A.

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N2 - 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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