Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency.
Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency.
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DOI：
10.1016/j.bbadis.2010.06.007
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发表时间：
2010-11
影响因子：
6.2
通讯作者：
Wevers, Ron A.
中科院分区：
文献类型：
--
作者：
Engelke, Udo F. H.;Zijlstra, Fokje S. M.;Mochel, Fanny;Valayannopoulos, Vassili;Rabier, Daniel;Kluijtmans, Leo A. J.;Perl, Andras;Verhoeven-Duif, Nanda M.;de Lonlay, Pascale;Wamelink, Mirjam M. C.;Jakobs, Cornelis;Morava, Eva;Wevers, Ron A.
关键词：
景天庚酮糖、阿糖醇、核糖醇和甘露糖醇已被鉴定为TALDO缺乏症的关键诊断代谢物。使用1H-NMR光谱法和GC-质谱法分析来自6名TALDO缺陷型患者和TALDO缺陷型敲除小鼠的尿液。我们的数据证实了TALDO缺陷患者的已知代谢特征。β-呋喃糖形式是TALDO缺陷患者中主要的景天庚酮糖异头体。在所有患者和TALDO基因敲除小鼠中，赤藓糖酸被鉴定为主要的异常代谢物，这暗示了这种疾病中的一种未知的生化途径。一个假定的序列的酶促反应，导致形成阿托膦酸。柠檬酸循环中间体2-氧代谷氨酸和富马酸的尿浓度在大多数TALDO缺陷患者中增加，但在基因敲除小鼠中没有增加。赤藓糖酸是TALDO缺乏症的一种新的主要标志。导致其产生的途径也可能在健康人类中发挥作用。在TALDO缺陷患者中，通过该途径的通量增加。柠檬酸循环中间产物增加的发现提示TALDO缺乏症中线粒体代谢紊乱。
Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency. Urine from 6 TALDO-deficient patients and TALDO-deficient knock-out mice were analyzed using 1H-NMR spectroscopy and GC–mass spectrometry. 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. 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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影响因子：
4.2
作者：
Wamelink, MMC;Smith, DEC;Verhoeven, NM
通讯作者：
Verhoeven, NM
影响因子：
4.2
作者：
Wamelink, M. M. C.;Struys, E. A.;Jakobs, C.
通讯作者：
Jakobs, C.
影响因子：
4.2
作者：
Verhoeven, NM;Wallot, M;Jakobs, C
通讯作者：
Jakobs, C
影响因子：
4.2
作者：
Wamelink, M. M.;Smith, D. E.;Jakobs, C.
通讯作者：
Jakobs, C.
影响因子：
3.5
作者：
Kardon, Tamas;Stroobant, Vincent;Van Schaftingen, Emile
通讯作者：
Van Schaftingen, Emile