Summary of Study ST001860
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 PR001173. The data can be accessed directly via it's Project DOI: 10.21228/M8341K 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 | ST001860 |
| Study Title | Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters |
| Study Type | Manuscript |
| Study Summary | 8988T cells treated with methyl acetate or 1 mM of alpha-ketoglutarate disodium salt or 1 mM of dimethyl-alpha-ketoglutarate for 3 hours prior to rapid quenching of metabolism and extraction of metabolites in 80% methanol (-80°C) containing internal QC standards. |
| Institute | University of British Columbia |
| Last Name | Parker |
| First Name | Seth |
| Address | 950 W 28th Ave, 2099, Vancouver, British Columbia, Canada V6H 0B3 |
| seth.parker@bcchr.ca | |
| Phone | 6048753121 |
| Submit Date | 2021-05-26 |
| Num Groups | 3 |
| Total Subjects | 9 |
| Num Males | n/a |
| Num Females | n/a |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-08-04 |
| Release Version | 1 |
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Project:
| Project ID: | PR001173 |
| Project DOI: | doi: 10.21228/M8341K |
| Project Title: | Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters |
| Project Type: | Manuscript |
| Project Summary: | α-ketoglutarate (KG), also referred to as 2-oxoglutarate, is a key intermediate of cellular metabolism with pleiotropic functions. Cell-permeable esterified analogs are widely used to study the role of KG in governing bioenergetic and amino acid metabolism and DNA, RNA, and protein hydroxylation reactions, as cellular membranes are thought to be impermeable to KG. Here we show that esterified KG analogs rapidly hydrolyze in aqueous media, yielding KG that, in contrast to prevailing assumptions, can be imported by many cell lines. Esterified KG analogs exhibit spurious KG-independent effects on cellular metabolism, including extracellular acidification, arising from rapid hydrolysis and de-protonation of α-ketoesters, and significant analog-specific inhibitory effects on glycolysis or mitochondrial respiration. In many cell lines, imported KG metabolizes to succinate in the cytosol, and we observe minimal KG utilization for mitochondrial metabolism in normal culture conditions. These findings demonstrate that nuclear and cytosolic KG-dependent reactions may derive KG from functionally distinct subcellular pools and sources. |
| Institute: | University of British Columbia |
| Department: | Biochemistry & Molecular Biology |
| Last Name: | Parker |
| First Name: | Seth |
| Address: | 950 W 28th Ave, Room 2099, Vancouver, British Columbia, Canada V6H 0B3 |
| Email: | seth.parker@bcchr.ca |
| Phone: | 6048753121 |
