Summary of Study ST002563

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001653. The data can be accessed directly via it's Project DOI: 10.21228/M81Q6Q This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002563
Study TitleMetabolomic profiling of PMM2-CDG after siRNA mediated KD of AKR1b1
Study SummaryAbnormal polyol metabolism has been predominantly associated with diabetes, where excess glucose is converted to sorbitol by aldose reductase (AR). Recently, abnormal polyol metabolism has also been implicated in phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), and epalrestat, an AR inhibitor, proposed as a potential therapy for this disorder. Given that the PMM enzyme is not closely connected to polyol metabolism, and, unlike in diabetes, PMM2-CDG does not present with hyperglycemia in blood, the increased polyol production, and the therapeutic mechanism of epalrestat in PMM2-CDG remained largely elusive. PMM2-CDG is caused by deficiency of the PMM enzyme and results in a depletion of mannose-1-P and guanosine diphosphate mannose (GDP-mannose), which is essential for glycosylation. Here, we show that apart from glycosylation abnormalities, PMM2 deficiency also leads to changes in intracellular glucose flux, which results in an increase in intracellular polyols. Ssing tracer glucose studies, we demonstrate that AR inhibition diverts glucose flux away from polyol production towards the synthesis of sugar nucleotides.
Mayo Clinic
Last NameRadenkovic
First NameSilvia
Address200 2nd Ave SW Rochester MN, USA
Phone507(77) 6-6107
Submit Date2023-04-15
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-07-18
Release Version1
Silvia Radenkovic Silvia Radenkovic application/zip

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Combined analysis:

Analysis ID AN004224
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters Acquity
Column Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Units AUC


Chromatography ID:CH003133
Chromatography Summary:C18 iP REVERSE PHASE
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
Column Temperature:40
Flow Gradient:The gradient started with 5% of solvent B and 95% solvent A and remained at 5% B until 2 min post injection. A linear gradient to 37% B was carried out until 7 min and increased to 41% until 14 min. Between 14 and 26 minutes the gradient increased to 95% of B and remained at 95% B for 4 minutes. At 30 min the gradient returned to 5% B. The chromatography was stopped at 40 min.
Flow Rate:0.25 mL/min
Solvent A:100% water; 10mM tributylamine; 15mM acetic acid
Solvent B:100% methanol
Chromatography Type:Reversed phase