Identification of escherichia coli by detection of hydroquinone uracil in the urine system

Maeda, Kenji; Shiraishi, Sanshiro; Sakamoto, Nobuo; Ohki, Toyokazu; Hosoi, Masaharu; Ohta, Kouji; Yamanaka, Naoki

doi:10.1016/0378-4347(85)80130-4

Cited by 4 publications

(1 citation statement)

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“…In addition, there are relatively few citations for 2,3-DHBA. The presence of this metabolite in human urine has been documented on a limited number of occasions [ 38 , 40 , 58 , 59 , 60 , 61 , 62 ] and has also been described in the mouse [ 63 ] and a single dog with insulin-dependent diabetes mellitus (IDDM) [ 38 ]. The observation of abnormal threonine metabolism to 2,3-DHBA in both children and a dog with IDDM [ 38 ] raises the question as to whether or not our observations of elevated plasma 2,3-DHBA in AML with mutated IDH1/2 could be due to diabetes.…”

Section: Discussionmentioning

confidence: 99%

(2R,3S)-Dihydroxybutanoic Acid Synthesis as a Novel Metabolic Function of Mutant Isocitrate Dehydrogenase 1 and 2 in Acute Myeloid Leukemia

Idle

Seipel

Bacher

et al. 2020

Cancers

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Acute myeloid leukemia (AML) frequently harbors mutations in isocitrate 1 (IDH1) and 2 (IDH2) genes, leading to the formation of the oncometabolite (2R)-hydroxyglutaric acid (2R-HG) with epigenetic consequences for AML proliferation and differentiation. To investigate if broad metabolic aberrations may result from IDH1 and IDH2 mutations in AML, plasma metabolomics was conducted by gas chromatography–mass spectrometry (GC–MS) on 51 AML patients, 29 IDH1/2 wild-type (WT), 9 with IDH1R132, 12 with IDH2R140 and one with IDH2R172 mutations. Distinct metabolic differences were observed between IDH1/2 WT, IDH1R132 and IDH2R140 patients that comprised 22 plasma metabolites that were mainly amino acids. Only two plasma metabolites were statistically significantly different (p < 0.0001) between both IDH1R132 and WT IDH1/2 and IDH2R140 and WT IDH1/2, specifically (2R)-hydroxyglutaric acid (2R-HG) and the threonine metabolite (2R,3S)-dihydroxybutanoic acid (2,3-DHBA). Moreover, 2R-HG correlated strongly (p < 0.0001) with 2,3-DHBA in plasma. One WT patient was discovered to have a D-2-hydroxyglutarate dehydrogenase (D2HGDH) A426T inactivating mutation but this had little influence on 2R-HG and 2,3-DHBA plasma concentrations. Expression of transporter genes SLC16A1 and SLC16A3 displayed a weak correlation with 2R-HG but not 2,3-DHBA plasma concentrations. Receiver operating characteristic (ROC) analysis demonstrated that 2,3-DHBA was a better biomarker for IDH mutation than 2R-HG (Area under the curve (AUC) 0.861; p < 0.0001; 80% specificity; 87.3% sensitivity). It was concluded that 2,3-DHBA and 2R-HG are both formed by mutant IDH1R132, IDH2R140 and IDH2R172, suggesting a potential role of 2,3-DHBA in AML pathogenesis.

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