NDLI: Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.

Please wait, while we are loading the content...

Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program.

Anthocyanin analysis in banana fruit--a mistake.

Hidden vegetables: an effective strategy to reduce energy intake and increase vegetable intake in adults.

Daily consumption of vitamin D- or vitamin D + calcium-fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial.

Low-carbohydrate diet scores and risk of type 2 diabetes in men.

Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971-2006.

Marked differences in gustatory and gastrointestinal sensitivity to oleic acid between lean and obese men.

Is there really a negative association between waist circumference and height in adults?

Oral acetyl-l-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled $study^{1},^{2},^{3}$

Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort.

The association between breastfeeding and the cardiovascular system in early childhood.

Randomized trial of a behavioral intervention to prevent excessive gestational weight gain: the Fit for Delivery Study.

Sensing of energy and nutrients by AMP-activated protein kinase.

Fundamental misunderstanding of the relation between energy density (kcal/g) and energy cost (\$/kcal).

Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women.

Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis.

Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.

Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288,498 men and women.

Confronting reality: pitfalls of calorie posting.

Genome-wide association studies of alcohol intake--a promising cocktail?

Year: 2011 Volume: 93 Issue: 3

Year: 2011 Volume: 93 Issue: 2

Year: 2011 Volume: 93 Issue: 1

Year: 2010 Volume: 92

Year: 2010 Volume: 91

Year: 2009 Volume: 90

Year: 2009 Volume: 89

Year: 2008 Volume: 88

Year: 2008 Volume: 87

Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Beaudin, Anna E. Abarinov, Elena V. Noden, Drew M. Perry, Cheryll A. Chu, Stephanie Stabler, Sally P. Allen, Robert H. Stover, Patrick J.
Description	Country affiliation: United States Author Affiliation: Beaudin AE ( Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.)
Abstract	BACKGROUND: Folic acid supplementation prevents the occurrence and recurrence of neural tube defects (NTDs), but the causal metabolic pathways underlying folic acid-responsive NTDs have not been established. Serine hydroxymethyltransferase (SHMT1) partitions folate-derived one-carbon units to thymidylate biosynthesis at the expense of cellular methylation, and therefore SHMT1-deficient mice are a model to investigate the metabolic origin of folate-associated pathologies. OBJECTIVES: We examined whether genetic disruption of the Shmt1 gene in mice induces NTDs in response to maternal folate and choline deficiency and whether a corresponding disruption in de novo thymidylate biosynthesis underlies NTD pathogenesis. DESIGN: Shmt1 wild-type, Shmt1(+/-), and Shmt1(-/-) mice fed either folate- and choline-sufficient or folate- and choline-deficient diets were bred, and litters were examined for the presence of NTDs. Biomarkers of impaired folate metabolism were measured in the dams. In addition, the effect of Shmt1 disruption on NTD incidence was investigated in Pax3(Sp) mice, an established folate-responsive NTD mouse model. RESULTS: Shmt1(+/-) and Shmt1(-/-) embryos exhibited exencephaly in response to maternal folate and choline deficiency. Shmt1 disruption on the Pax3(Sp) background exacerbated NTD frequency and severity. Pax3 disruption impaired de novo thymidylate and purine biosynthesis and altered amounts of SHMT1 and thymidylate synthase protein. CONCLUSIONS: SHMT1 is the only folate-metabolizing enzyme that has been shown to affect neural tube closure in mice by directly inhibiting folate metabolism. These results provide evidence that disruption of Shmt1 expression causes NTDs by impairing thymidylate biosynthesis and shows that changes in the expression of genes that encode folate-dependent enzymes may be key determinates of NTD risk.
File Format	HTM / HTML
ISSN	00029165
e-ISSN	19383207
DOI	10.3945/ajcn.110.002766
Journal	American Journal of Clinical Nutrition
Issue Number	4
Volume Number	93
Language	English
Publisher	American Society for Nutrition
Publisher Date	2011-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Nutritional Sciences Folic Acid Deficiency Complications Folic Acid Pharmacology Glycine Hydroxymethyltransferase Genetics Mutation Neural Tube Defects Etiology Thymidine Monophosphate Biosynthesis Vitamin B Complex Animals Biological Markers Blood Choline Choline Deficiency Disease Models, Animal Gene Expression Metabolism Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Knockout Purines Severity Of Illness Index Thymidylate Synthase Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Medicine

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

Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice.

Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice 1 2 3 4

Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency.

Azoxymethane-induced colon carcinogenesis in mice occurs independently of de novo thymidylate synthesis capacity.

Neural Tube Defects, Folic Acid and Methylation

One-carbon metabolism-genome interactions in folate-associated pathologies.

Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice 1 2 3 4 5

C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice.

Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.

Similar Documents

Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice.

Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice 1 2 3 4

Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency.

Azoxymethane-induced colon carcinogenesis in mice occurs independently of de novo thymidylate synthesis capacity.

Neural Tube Defects, Folic Acid and Methylation

One-carbon metabolism-genome interactions in folate-associated pathologies.

Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

Dietary folate, but not choline, modifies neural tube defect risk in Shmt1 knockout mice 1 2 3 4 5

C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice.

Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.