Low Folate Status and Relationship with Betaine and Homocysteine

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Abstract

Folate and betaine participate in homocysteine metabolism through the methionine synthase (MS) and betaine-homocysteine methyltransferase (BMHT) pathways, respectively. The ubiquitous MS pathway depends on 5-methyltetrahydrofolate and cobalamin as cofactors in the remethylation of homocysteine to methionine. When folate and cobalamin supply are adequate, homocysteine remethylation to methionine is predominantly by the MS pathway. The BHMT pathway appears to play an important role in very early embryogenesis and fetal development (in animal studies) but is then limited mainly to the kidney and liver in human adults.

Low or suboptimal folate status still affects non-supplement users and low consumers of voluntarily fortified foods in populations where mandatory fortification with folic acid is absent.

Limited dietary folate and/or cobalamin intake impairs homocysteine remethylation via the MS pathway thus leading to increased blood homocysteine and reduced methionine synthesis. Evidence from in vitro and animal studies shows that the BHMT pathway is upregulated when folate status is low. Preliminary evidence supports the hypothesis that homocysteine remethylation by BHMT is enhanced when the MS pathway is impaired due to low folate status in human adults and during pregnancy. Further research is required to demonstrate that BHMT activity increases in response to low folate status and to determine the extent to which the BHMT pathway can compensate for MS pathway impairment.

Keywords

Folate Betaine Cobalamin Homocysteine Methionine synthase Betaine-homocysteine methyltransferase Methionine 

List of Abbreviations

1C

One carbon

1CM

One carbon metabolism

5,10-CH2THF

5,10-Methylenetetrahydrofolate

5-CH3THF

5-Methyltetrahydrofolate

BHMT

Betaine-homocysteine methyltransferase

CBS

Cystathionine-beta-synthase

CHDH

Choline dehydrogenase

DMG

Dimethylglycine

DMGDH

Dimethylglycine dehydrogenase

FAD

Flavin adenine dinucleotide

MS

Methionine synthase

MTHFR

Methylenetetrahydrofolate reductase

NTDs

Neural tube defects

PML

Post-methionine load

PMNS

Pune Maternal Nutrition Study

SAM

S-adenosyl methionine

SARDH

Sarcosine dehydrogenase

SNPs

Single nucleotide polymorphisms

tHcy

Fasting total plasma homocysteine

THF

Tetrahydrofolate

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Unit of Preventive Medicine and Public Health, Department of Basic Medical Sciences, Faculty of Medicine and Health SciencesIISPV, Universitat Rovira i VirgiliReus, TarragonaSpain
  2. 2.Biomedical Research Networking Center for the Pathophysiology of ObesityCarlos III Institute of HealthMadridSpain

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