TY - JOUR
T1 - Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency
AU - Engelke, Udo F.H.
AU - Zijlstra, Fokje S.M.
AU - Mochel, Fanny
AU - Valayannopoulos, Vassili
AU - Rabier, Daniel
AU - Kluijtmans, Leo A.J.
AU - Perl, András
AU - Verhoeven-Duif, Nanda M.
AU - de Lonlay, Pascale
AU - Wamelink, Mirjam M.C.
AU - Jakobs, Cornelis
AU - Morava, Éva
AU - Wevers, Ron A.
PY - 2010/11
Y1 - 2010/11
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.
AB - 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.
KW - 2-Oxoglutaric acid
KW - Citric acid cycle intermediates
KW - Erythronic acid
KW - NMR spectroscopy
KW - Pentose phosphate pathway
KW - Polyols
KW - Sedoheptulose
KW - Transaldolase deficiency
UR - http://www.scopus.com/inward/record.url?scp=77956651793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956651793&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2010.06.007
DO - 10.1016/j.bbadis.2010.06.007
M3 - Article
C2 - 20600873
AN - SCOPUS:77956651793
SN - 0925-4439
VL - 1802
SP - 1028
EP - 1035
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 11
ER -