Novel insights into L-2-hydroxyglutaric aciduria: Mass isotopomer studies reveal 2-oxoglutaric acid as the metabolic precursor of L-2-hydroxyglutaric acid
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- Struys, E.A., Gibson, K.M. & Jakobs, C. J Inherit Metab Dis (2007) 30: 690. doi:10.1007/s10545-007-0697-5
Employing lymphoblasts derived from two non related patients with l-2-HG aciduria, we examined the origin of l-2-hydroxyglutaric acid (l-2-HG) through incubation with [13C6]glucose and [2H5]glutamic acid. Formation of labelled 2-ketoglutaric acid (2-KG), citric acid and l-2-HG was determined by GC-MS. The quantitative and qualitative isotopomer pattern following incubation with [13C6]glucose was identical for all end-products. Incubations with [2H5]glutamic acid as precursor revealed the formation of identical isotopomers for 2-KG and l-2-HG. Our data indicate that 2-KG is the metabolic precursor of l-2-HG, adding to previous studies which revealed that 2-KG is the metabolic precursor of d-2-HG. These data suggest that 2-KG has a pathophysiological role in combined d/l-2-HG aciduria.