Summary of project PR002736
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 PR002736. The data can be accessed directly via it's Project DOI: 10.21228/M80P0S This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002736 |
| Project DOI: | doi: 10.21228/M80P0S |
| Project Title: | Kinetic analysis of cellular fates of cyclic 3-phosphoglyceric anhydride reveals a crucial role of DJ-1 and glutathione in protecting biomolecules from acylation. |
| Project Summary: | A spontaneous cyclization of 1,3-bisphosphoglycerate produces a highly reactive cyclic 3- phosphoglyceric anhydride (cPGA) which damages cellular nucleophiles through indiscriminate acylation. Although evidence suggests that most of the cPGA is inactivated by DJ-1, a highly efficient cPGA hydrolase, it is not known what percentage of cPGA is inactivated by DJ-1 and how the remaining cPGA is distributed in reactions with major cellular nucleophiles. Here, we use a kinetic approach to model cellular fates of cPGA in HCT116 cells. Quantitative assessment of DJ-1 activity and reactivity of cellular nucleophiles toward cPGA indicates that up to 99% of intracellular cPGA is inactivated by DJ-1. Unexpectedly, more than half of cPGA that escapes the inactivation by DJ-1 is predicted to react with the thiol group of glutathione (GSH) to produce a corresponding thioester S-D-3-phosphoglyceroyl glutathione (pgGS). We found that pgGS is unstable and decomposes back to GSH and cPGA with a half-life of 80 minutes providing DJ-1 with another chance to inactivate cPGA. Apart from spontaneous decomposition, pgGS is efficiently hydrolyzed by Glyoxalase II (GlxII), therefore a significant fraction of cPGA that escapes hydrolysis by DJ-1 is trapped by GSH and subsequently detoxified. Experiments with DJ-1-null cells revealed that depletion of GSH causes a multi-fold increase in cellular level of N-glyceroyl glutamine confirming that a reversible formation of pgGS in reaction of cPGA with GSH serves as a second line of defense against acylation of biomolecules by cPGA. |
| Institute: | National Laboratory Astana |
| Last Name: | Akhmadi |
| First Name: | Aizhan |
| Address: | Kabanbay Batyr Ave 53, Astana, Kazakhstan |
| Email: | aizhan.tkirova@nu.edu.kz |
| Phone: | +77172694682 |
| Project Comments: | I |
Summary of all studies in project PR002736
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004322 | Evidence for glutathione-mediated protection against cPGA-induced acylation in human HCT116 DJ-1 knockout cells. | Homo sapiens | National Laboratory Astana | MS | 2025-11-20 | 1 | 9 | Uploaded data (7.2G)* |
