title: Investigations by mass isotopomer analysis of the formation of D-2-hydroxyglutarate by cultured lymphoblasts from two patients with D-2-hydroxyglutaric aciduria.
abstract: 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-(13)C(6)]glucose or [(2)H(5)]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-(13)C(6)]glucose and [(2)H(5)]glutamate incubations, revealed that 2-KG interconverts rapidly to D-2-HG and that D-2-HG is formed within the mitochondria.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. e.struys@vumc.nl
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Struys
authors.forename: Nanda M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: Henri
authors.initials: H
authors.lastname: Brunengraber
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D002460:Cell Line; D002951:Citrates / Q000378:metabolism; D005977:Glutarates / Q000378:metabolism* / Q000652:urine*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008954:Models, Biological; D013237:Stereoisomerism
chemical_list: D002951:Citrates; D005977:Glutarates; C019417:alpha-hydroxyglutarate