Summary of project PR001856
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 PR001856. The data can be accessed directly via it's Project DOI: 10.21228/M8T42G This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001856 |
| Project DOI: | doi: 10.21228/M8T42G |
| Project Title: | Glycine homeostasis requires reverse SHMT flux |
| Project Type: | LCMS metabolomics |
| Project Summary: | The folate-dependent enzyme serine hydroxymethyltransferase (SHMT) reversibly converts serine into glycine and a tetrahydrofolate-bound one-carbon unit. Such one-carbon unit production plays a critical role in development, the immune system, and cancer. Using rodent models, here we show that the whole-body SHMT flux acts to net consume rather than produce glycine. Pharmacological inhibition of whole-body SHMT1/2 and genetic knockout of liver SHMT2 elevated circulating glycine levels up to eight-fold. Stable isotope tracing revealed that the liver converts glycine to serine, which is then converted by serine dehydratase into pyruvate and burned in the tricarboxylic acid cycle. In response to diets deficient in serine and glycine, de novo biosynthetic flux was unaltered but SHMT2- and serine dehydratase-mediated catabolic flux was lower. Thus, glucose-derived serine synthesis does not respond to systemic demand. Instead, circulating serine and glycine homeostasis is maintained through variable consumption, with liver SHMT2 a major glycine-consuming enzyme. |
| Institute: | Princeton University |
| Department: | Department of Chemistry |
| Laboratory: | Josh Rabinowitz |
| Last Name: | McBride |
| First Name: | Matthew |
| Address: | Carl Icahn Lab, South Drive, Princeton, NJ 08544 |
| Email: | matthewmcbride@princeton.edu |
| Phone: | 8567457389 |
Summary of all studies in project PR001856
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002980 | Water soluble metabolomics in mice upon loss of SHMT | Mus musculus | Princeton University | MS* | 2023-12-12 | 1 | 36 | Uploaded data (918.6M)* |
