NDLI: Mthfd1 Is an Essential Gene in Mice and Alters Biomarkers of Impaired One-carbon Metabolism

Content Provider	Journal of Biological Chemistry (JBC)
Author	MacFarlane, Amanda J. Perry, Cheryll A. Girnary, Hussein H. Gao, Dacao Allen, Robert H. Stabler, Sally P. Shane, Barry Stover, Patrick J.
Abstract	Cytoplasmic folate-mediated one carbon (1C) metabolism functions to carry and activate single carbons for the de novo synthesis of purines, thymidylate, and for the remethylation of homocysteine to methionine. C1 tetrahydrofolate (THF) synthase, encoded by Mthfd1, is an entry point of 1Cs into folate metabolism through its formyl-THF synthetase (FTHFS) activity that catalyzes the ATP-dependent conversion of formate and THF to 10-formyl-THF. Disruption of FTHFS activity by the insertion of a gene trap vector into the Mthfd1 gene results in embryonic lethality in mice. Mthfd1gt/+ mice demonstrated lower hepatic adenosylmethionine levels, which is consistent with formate serving as a source of 1Cs for cellular methylation reactions. Surprisingly, Mthfd1gt/+ mice exhibited decreased levels of uracil in nuclear DNA, indicating enhanced de novo thymidylate synthesis, and suggesting that serine hydroxymethyltransferase and FTHFS compete for a limiting pool of unsubstituted THF. This study demonstrates the essentiality of the Mthfd1 gene and indicates that formate-derived 1Cs are utilized for de novo purine synthesis and the remethylation of homocysteine in liver. Further, the depletion of cytoplasmic FTHFS activity enhances thymidylate synthesis, affirming the competition between thymidylate synthesis and homocysteine remethylation for THF cofactors.
Related Links	http://www.jbc.org/content/284/3/1533.abstract
Ending Page	1539
Starting Page	1533
Page Count	7
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	3
Volume Number	284
DOI	10.1074/jbc.M808281200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2009-01-16
Access Restriction	Open
Subject Keyword	Metabolism and Bioenergetics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Mthfd1 Is an Essential Gene in Mice and Alters Biomarkers of Impaired One-carbon Metabolism*

Mthfd1 is an essential gene in mice and alters biomarkers of impaired one-carbon metabolism.

Disruption of the Mthfd1 Gene Reveals a Monofunctional 10-Formyltetrahydrofolate Synthetase in Mammalian Mitochondria

A Thyroid Hormone Receptor α Gene Mutation (P398H) Is Associated with Visceral Adiposity and Impaired Catecholamine-stimulated Lipolysis in Mice

Exercise Capacity of Mice Genetically Lacking Muscle Glycogen Synthase IN MICE, MUSCLE GLYCOGEN IS NOT ESSENTIAL FOR EXERCISE

Cytoplasmic Serine Hydroxymethyltransferase Regulates the Metabolic Partitioning of Methylenetetrahydrofolate but Is Not Essential in Mice

Hormone-sensitive Lipase Null Mice Exhibit Signs of Impaired Insulin Sensitivity whereas Insulin Secretion Is Intact

Fumarate Is an Essential Intermediary Metabolite Produced by the Procyclic Trypanosoma brucei

Monothiol Glutaredoxin-1 Is an Essential Iron-Sulfur Protein in the Mitochondrion of African Trypanosomes

Mthfd1 Is an Essential Gene in Mice and Alters Biomarkers of Impaired One-carbon Metabolism

Similar Documents

Mthfd1 Is an Essential Gene in Mice and Alters Biomarkers of Impaired One-carbon Metabolism*

Mthfd1 is an essential gene in mice and alters biomarkers of impaired one-carbon metabolism.

Disruption of the Mthfd1 Gene Reveals a Monofunctional 10-Formyltetrahydrofolate Synthetase in Mammalian Mitochondria

A Thyroid Hormone Receptor α Gene Mutation (P398H) Is Associated with Visceral Adiposity and Impaired Catecholamine-stimulated Lipolysis in Mice

Exercise Capacity of Mice Genetically Lacking Muscle Glycogen Synthase IN MICE, MUSCLE GLYCOGEN IS NOT ESSENTIAL FOR EXERCISE

Cytoplasmic Serine Hydroxymethyltransferase Regulates the Metabolic Partitioning of Methylenetetrahydrofolate but Is Not Essential in Mice

Hormone-sensitive Lipase Null Mice Exhibit Signs of Impaired Insulin Sensitivity whereas Insulin Secretion Is Intact

Fumarate Is an Essential Intermediary Metabolite Produced by the Procyclic Trypanosoma brucei

Monothiol Glutaredoxin-1 Is an Essential Iron-Sulfur Protein in the Mitochondrion of African Trypanosomes

Mthfd1 Is an Essential Gene in Mice and Alters Biomarkers of Impaired One-carbon Metabolism