Investigations by mass isotopomer analysis of the formation of D‐2‐hydroxyglutarate by cultured lymphoblasts from two patients with D‐2‐hydroxyglutaric aciduria

FEBS Letters

Jakobs, Cornelis¹  Brunengraber, Henri²  Struys, Eduard A.¹  Verhoeven, Nanda M.¹ 

[1] Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands;Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA

关键词: D-2-Hydroxyglutaric aciduria;    D-2-Hydroxyglutarate;    Origin;    Citric acid cycle;    Mass isotopomer analysis;    2-Ketoglutarate;    Citrate;    GC-MS;   

DOI  :  10.1016/S0014-5793(03)01459-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

D-2-Hydroxyglutaric aciduria is an inborn error of metabolism first described in 1980. To date, more than 40 patients have been diagnosed with this disease. To identify the metabolic precursor of D-2-hydroxyglutarate (D-2-HG), cultured human lymphoblasts from two patients with D-2-HG aciduria were grown in culture medium supplemented with [U-¹³C₆]glucose or [²H₅]glutamate. Mass isotopomer distribution measurements of D-2-HG, 2-ketoglutarate (2-KG) and citrate were performed by gas chromatography-mass spectrometry. The mass isotopomer distributions in D-2-HG, 2-KG and citrate, following [U-¹³C₆]glucose and [²H₅]glutamate incubations, revealed that 2-KG interconverts rapidly to D-2-HG and that D-2-HG is formed within the mitochondria.

【 授权许可】

Unknown