Summary of Study ST002561
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
Study ID | ST002561 |
Study Title | Metabolomic profiling of PMM2-CDG zebrafish in presence and absence of epalrestat |
Study Summary | Abnormal 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. Targeting AR with epalrestat decreases polyol levels and increases GDP-mannose in vivo in pmm2 mutant zebrafish. |
Institute | Mayo Clinic |
Last Name | Radenkovic |
First Name | Silvia |
Address | 200 2nd Ave SW Rochester MN, USA |
radenkovic.silvia@mayo.edu | |
Phone | 507(77) 6-6107 |
Submit Date | 2023-04-14 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2023-07-18 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN004221 | AN004222 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | Reversed phase | HILIC |
Chromatography system | Waters Acquity | Agilent Infinity |
Column | C-18: Acquity UPLC -HSS T3 1. 8 µm; 2.1 x 150 mm, Waters | Poroshell 120 HILIC-Z PEEK Column 2.1x 150mm, 5 um |
MS Type | ESI | ESI |
MS instrument type | Orbitrap | Orbitrap |
MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Focus |
Ion Mode | NEGATIVE | NEGATIVE |
Units | AUC | AUC |
Chromatography:
Chromatography ID: | CH003130 |
Chromatography Summary: | Reverse phase, IP, C18 column |
Instrument Name: | Waters Acquity |
Column Name: | C-18: Acquity UPLC -HSS T3 1. 8 µm; 2.1 x 150 mm, Waters |
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 |
Chromatography ID: | CH003131 |
Chromatography Summary: | HILIC |
Instrument Name: | Agilent Infinity |
Column Name: | Poroshell 120 HILIC-Z PEEK Column 2.1x 150mm, 5 um |
Column Temperature: | 25 |
Flow Gradient: | A linear gradient was carried out starting with 90% solvent A and 10% solvent B. From 2 to 12 min the gradient changed to 60% B. The gradient was kept on 60% B for 3 minutes and followed by a decrease to 10% B. The chromatography was stopped at 25 min |
Flow Rate: | 0.25 mL/min |
Solvent A: | 100% acetonitrile |
Solvent B: | 100% water; 10 mM sodium acetate, pH 9.3 |
Chromatography Type: | HILIC |