Novel insights into L-2-hydroxyglutaric aciduria: Mass isotopomer studies reveal 2-oxoglutaric acid as the metabolic precursor of L-2-hydroxyglutaric acid

被引：25

作者：

Struys, E. A.

Gibson, K. M.

Jakobs, C.

机构：

[1] Vrije Univ Amsterdam Med Ctr, Clin Chem, Metab Unit, NL-1081 HV Amsterdam, Netherlands

[2] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pediat,Biochem Genet Lab,Div Med Genet, Pittsburgh, PA USA

[3] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Pathol,Biochem Genet Lab,Div Med Genet, Pittsburgh, PA USA

[4] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Dept Human Genet,Biochem Genet Lab,Div Med Genet, Pittsburgh, PA USA

来源：

JOURNAL OF INHERITED METABOLIC DISEASE | 2007年 / 30卷 / 05期

关键词：

D O I：

10.1007/s10545-007-0697-5

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 [C-13(6)]glucose and [H-2(5)]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 [C-13(6)]glucose was identical for all end-products. Incubations with [H-2(5)]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.

引用

页码：690 / 693

页数：4

共 9 条

[1] L-2-HYDROXYGLUTARIC ACIDEMIA - CLINICAL AND BIOCHEMICAL FINDINGS IN 12 PATIENTS AND PRELIMINARY-REPORT ON L-2-HYDROXYACID DEHYDROGENASE [J].