| Create Account | login

login

Publication

Glycine N-methyltransferase deletion in mice diverts carbon flux from
gluconeogenesis to pathways that utilize excess methionine cycle intermediates.

Authors	Hughey CC, Trefts E, Bracy DP, James FD, Donahue EP, Wasserman DH
Submitted By	Submitted Externally on 8/20/2018
Status	Published
Journal	The Journal of biological chemistry
Year	2018
Date Published	7/1/2018
Volume : Pages	293 : 11944 - 11954
PubMed Reference	29891549
Abstract	Glycine N-methyltransferase (GNMT) is the most abundant liver methyltransferase regulating the availability of the biological methyl donor, S-adenosylmethionine (SAM). Moreover, GNMT has been identified to be down-regulated in hepatocellular carcinoma (HCC). Despite its role in regulating SAM levels and association of its down-regulation with liver tumorigenesis, the impact of reduced GNMT on metabolic reprogramming before the manifestation of HCC has not been investigated in detail. Herein, we used 2H/13C metabolic flux analysis in conscious, unrestrained mice to test the hypothesis that the absence of GNMT causes metabolic reprogramming. GNMT-null (KO) mice displayed a reduction in blood glucose that was associated with a decline in both hepatic glycogenolysis and gluconeogenesis. The reduced gluconeogenesis was due to a decrease in liver gluconeogenic precursors, citric acid cycle fluxes, and anaplerosis and cataplerosis. A concurrent elevation in both hepatic SAM and metabolites of SAM utilization pathways was observed in the KO mice. Specifically, the increase in metabolites of SAM utilization pathways indicated that hepatic polyamine synthesis and catabolism, transsulfuration, and de novo lipogenesis pathways were increased in the KO mice. Of note, these pathways utilize substrates that could otherwise be used for gluconeogenesis. Also, this metabolic reprogramming occurs before the well-documented appearance of HCC in GNMT-null mice. Together, these results indicate that GNMT deletion promotes a metabolic shift whereby nutrients are channeled away from glucose formation toward pathways that utilize the elevated SAM.

Back to Top

Store Credentials?

MMPC-Live web resource – Terms of Use

Warranty disclaimer and copyright notice

THE MMPC-Live MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".

The Mouse Metabolic Phenotyping Centers (MMPC-Live) is an NIDDK funded consortium and adheres to the NIH Data Sharing Policy.

MMPC-Live clients make their data freely available whereby MMPC-Live users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC-Live using the following text: 'The MMPC-Live data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (MMPC-Live, RRID:SCR_008997, www.mmpc.org)'. To cite specific MMPC-Live centers, please use the appropriate RRID available from the MMPC-Live website (https://www.mmpc.org/shared/centers.aspx).

Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC-Live CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.

It is expected that MMPC-Live users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC-Live (such as summary data) and any plots, tables or screenshots depicting those data.

It is possible for invalid or incomplete results to be presented on the MMPC-Live web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.

Prohibited use. Data contributors and data users may not use MMPC-Live in any unlawful manner, or in any manner that could impair MMPC-Live services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.

MMPC-Live is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.

Menu

Home

Contact

About MMPC

Animal Husbandry

Tests Data

Search Data

Analysis

Clients

MMPC Centers

Newsletter

Interested in receiving MMPC News?

Mouse Phenotyping
@NationalMMPC

2017 National MMPC. All Rights Reserved.