Impaired folate one-carbon metabolism causes formate-preventable hydrocephalus in glycine decarboxylase-deficient mice.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Impaired folate one-carbon metabolism causes formate-preventable hydrocephalus in glycine decarboxylase-deficient mice."

Ventriculomegaly and hydrocephalus are associated with loss of function of glycine decarboxylase (Gldc) in mice and in humans suffering from Non-Ketotic Hyperglycinemia (NKH), a neurometabolic disorder characterised by accumulation of excess glycine. Here, we showed that ventriculomegaly in Gldc-deficient mice is preceded by stenosis of the Sylvian aqueduct and malformation or absence of the sub-commissural organ and pineal gland. Gldc functions in the glycine cleavage system, a mitochondrial component of folate metabolism, whose malfunction results in accumulation of glycine and diminished supply of glycine-derived one-carbon units to the folate cycle. We showed that inadequate one-carbon supply, as opposed to excess glycine is the cause of hydrocephalus associated with loss of function of the glycine cleavage system. Maternal supplementation with formate prevented both ventriculomegaly, as assessed at pre-natal stages, and post-natal development of hydrocephalus in Gldc-deficient mice. Furthermore, ventriculomegaly was rescued by genetic ablation of 5,10-methylene tetrahydrofolate reductase (Mthfr), which results in retention of one-carbon groups in the folate cycle at the expense of transfer to the methylation cycle. In conclusion, a defect in folate metabolism can lead to pre-natal aqueduct stenosis and resultant hydrocephalus. These defects are preventable by maternal supplementation with formate, which acts as a one-carbon donor.


Journal Details

This article was published in the following journal.

Name: The Journal of clinical investigation
ISSN: 1558-8238


DeepDyve research library

PubMed Articles [10706 Associated PubMed Articles listed on BioPortfolio]

Folate as an Adjuvant Therapy in Methanol Poisoning.

Folate and its derivatives have long been used as an adjunctive treatment in methanol poisoning. Methanol is ultimately metabolized to formate, the toxic compound. The accumulation of formate can lead...

Formate concentrations in maternal plasma during pregnancy and in cord blood in a cohort of pregnant Canadian women: relations to genetic polymorphisms and plasma metabolites.

One-carbon metabolism, responsible for purine and thymidylate synthesis and transmethylation reactions, plays a critical role in embryonic and fetal development. Formate is a key player in one-carbon ...

Application of the Preventable Shunt Revision Rate to an Adult Population.

The Preventable Shunt Revision Rate (PSRR) was recently introduced in pediatric hydrocephalus as a quality metric for shunt surgery. We sought to implement the PSRR in an adult hydrocephalus populatio...

Alterations in folate-dependent one-carbon metabolism as colon cell transition from normal to cancerous.

Folate-dependent one-carbon cycle metabolism (FOCM) plays a critical role in maintaining genomic stability through regulating DNA biosynthesis, repair and methylation. Folate metabolites as well as ot...

Renewable methanol and formate as microbial feedstocks.

Methanol and formate are attractive microbial feedstocks as they can be sustainably produced from CO and renewable energy, are completely miscible, and are easy to store and transport. Here, we provid...

Clinical Trials [4228 Associated Clinical Trials listed on BioPortfolio]

Determinants of Formate Concentrations

Formate is an important metabolite, serving as a donor of one-carbon groups to the intracellular tetrahydrofolate pool. However, little is known of its circulating concentrations or of the...

Assessing Colonic Folate Absorption & Metabolism

Folate, a B-vitamin, is necessary in metabolic processes such as amino acid and nucleotide synthesis. Since folate cannot be synthesized by mammals, it must be consumed as foods and dietar...

Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development of NSCLC Patients

Non-small cell lung cancer (NSCLC) accounts for more than two-thirds of lung cancer, which is the leading cause of cancer deaths in Taiwan. The overall prognosis of NSCLC is poor with low ...

Impact of High-dose Folic Acid Supplementation on Pathways Linked to DNA Formation

Periconceptional supplementation with folic acid - the synthetic form of the B-vitamin folate - reduces the occurrence of adverse pregnancy outcomes such as spina bifida. The underlying bi...

Correspondence of Folate Dietary Intake and Biomarker Data

This NHANES analysis compares self-reported dietary folate with serum and red blood cell folate status in U.S. adults.

Medical and Biotech [MESH] Definitions

Flavoproteins that catalyze reversibly the reduction of carbon dioxide to formate. Many compounds can act as acceptors, but the only physiologically active acceptor is NAD. The enzymes are active in the fermentation of sugars and other compounds to carbon dioxide and are the key enzymes in obtaining energy when bacteria are grown on formate as the main carbon source. They have been purified from bovine blood. EC

A carbon-nitrogen ligase that catalyzes the formation of 10-formyltetrahydrofolate from formate and tetrahydrofolate in the presence of ATP. In higher eukaryotes the enzyme also contains METHYLENETETRAHYDROFOLATE DEHYDROGENASE (NADP+) and METHENYLTETRAHYDROFOLATE CYCLOHYDROLASE activity.

Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, INTRACRANIAL HYPERTENSION; HEADACHE; lethargy; URINARY INCONTINENCE; and ATAXIA (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, INTRACRANIAL HEMORRHAGES; CENTRAL NERVOUS SYSTEM INFECTIONS; BRAIN NEOPLASMS; CRANIOCEREBRAL TRAUMA; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from CEREBRAL INFARCTION and other conditions.

An inhibitor of folate metabolism. It is used as a coccidiostat in poultry.

A subtype of GPI-anchored folate receptors that is expressed in PLACENTA and hematopoietic cells.

Quick Search

DeepDyve research library

Relevant Topic

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Article