Summary of project PR002184
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 PR002184. The data can be accessed directly via it's Project DOI: 10.21228/M89V56 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002184 |
| Project DOI: | doi: 10.21228/M89V56 |
| Project Title: | Restricting lysine normalizes toxic catabolites associated with ALDH7A1-deficiency in cells and mice |
| Project Type: | Manuscript |
| Project Summary: | Lysine metabolism converges at α-aminoadipic semialdehyde dehydrogenase (ALDH7A1). Rare loss-of-function mutations in ALDH7A1 cause a toxic accumulation of lysine catabolites, including piperideine 6-carboxylate (P6C), that are thought to cause fatal seizures in children unless strictly managed with dietary lysine reduction. In this study, we perform metabolomics and expression analysis of tissues from Aldh7a1-deficient mice, which reveal tissue-specific differences in lysine metabolism and other metabolic pathways. We also develop a fluorescent biosensor to characterize lysine transporter activity and identify competitive substrates that reduce the accumulation of lysine catabolites in ALDH7A1-deficient HEK293 cells. Lastly, we show that intravenous administration of lysine α-oxidase from Trichoderma viride reduces lysine and P6C levels by >80% in mice. Our results improve our understanding of lysine metabolism and make inroads towards improving therapeutic strategies for lysine catabolic disorders. |
| Institute: | University of British Columbia |
| Department: | Biochemistry & Molecular Biology |
| Laboratory: | Parker laboratory |
| Last Name: | Parker |
| First Name: | Seth |
| Address: | 950 W 28th Ave, Vancouver, British Columbia, V6H 0B3, Canada |
| Email: | seth.parker@bcchr.ca |
| Phone: | 6048753121 |
Summary of all studies in project PR002184
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003548 | Metabolomics of Aldh7a1-/- mice treated with lysine alpha-oxidase from Trichoderma viride | Mus musculus | University of British Columbia | MS | 2024-11-15 | 1 | 18 | Uploaded data (3.9G)* |
