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Metabolites
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Folate Absorption and Metabolism
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Folate Absorption and Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 14218

Special Issue Editor

Prof. Dr. Fabio Coppedè

E-Mail Website
Guest Editor
Department of Translational Research and new Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Interests: folate metabolism; polymorphisms of folate-related genes; medical genetics; epigenetics; DNA methylation; DNA repair
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dietary folates are essential B-group vitamins working as donors and acceptors of one-carbon units during the synthesis of nucleic acid precursors, amino acids, and S-adenosylmethionine (SAM), the major intracellular methylating agent.

Impairments in folate absorption and metabolism can lead to hyperhomocysteinemia, chromosome damage and malsegregation, point mutations, impaired cellular division, and epigenetic dysregulation. Indeed, several human diseases have been linked to inadequate folate intake from foods or are suspected to result from an impaired metabolism due to variants and polymorphisms of folate transporters and metabolic genes.

At present, there is a need to shed light on studies addressing this area and to critically review and analyze the available literature. Additional studies addressing previous questions in a deeper manner and with increased statistical power are warranted. Furthermore, the ever-growing field relating impaired folate metabolism to epigenetic changes is timely and attractive, also as an attempt to counteract disease-related epigenetic changes with dietary interventions.

The present Special Issue aims to collect research and review articles, as well as literature meta-analyses on the following topics or in similar areas related to folate absorption and metabolism:

  • Mechanisms of folate absorption and metabolism in humans;
  • Human diseases related to impaired folate absorption and metabolism;
  • Variants and polymorphisms of folate-related genes and human disease;
  • Epigenetic changes related to impaired folate absorption and metabolism;
  • Epigenetic changes related to polymorphisms of folate-related genes;
  • Folate metabolism and DNA methylation;
  • Epidemiological studies related to folic acid fortification of foods in human populations;
  • Dietary interventions (B-vitamins and folic acid supplements) in humans and animal models of human diseases (including those aimed to counteract disease-related epigenetic changes).

Prof. Fabio Coppedè
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • folate metabolism
  • folate transporters
  • polymorphisms of folate-related genes
  • epigenetics
  • DNA methylation
  • Dietary interventions

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Published Papers (3 papers)

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Research

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16 pages, 1371 KiB  
Article
The Key Role of Purine Metabolism in the Folate-Dependent Phenotype of Autism Spectrum Disorders: An In Silico Analysis
by Jan Geryk, Daniel Krsička, Markéta Vlčková, Markéta Havlovicová, Milan Macek, Jr. and Radka Kremlíková Pourová
Metabolites 2020, 10(5), 184; https://doi.org/10.3390/metabo10050184 - 6 May 2020
Cited by 10 | Viewed by 4809
Abstract
Folate deficiency in the critical developmental period has been repeatedly associated with an increased risk of Autism spectrum disorders (ASD), but the key pathophysiological mechanism has not yet been identified. In this work, we focused on identifying genes whose defect has similar consequences [...] Read more.
Folate deficiency in the critical developmental period has been repeatedly associated with an increased risk of Autism spectrum disorders (ASD), but the key pathophysiological mechanism has not yet been identified. In this work, we focused on identifying genes whose defect has similar consequences to folate depletion in the metabolic network. Within the Flux Balance Analysis (FBA) framework, we developed a method of blocked metabolites that allowed us to define the metabolic consequences of various gene defects and folate depletion. We identified six genes (GART, PFAS, PPAT, PAICS, ATIC, and ADSL) whose blocking results in nearly the same effect in the metabolic network as folate depletion. All of these genes form the purine biosynthetic pathway. We found that, just like folate depletion, the blockade of any of the six genes mentioned above results in a blockage of purine metabolism. We hypothesize that this can lead to decreased adenosine triphosphate (ATP) and subsequently, an S-adenosyl methionine (SAM) pool in neurons in the case of rapid cell division. Based on our results, we consider the methylation defect to be a potential cause of ASD, due to the depletion of purine, and consequently S-adenosyl methionine (SAM), biosynthesis. Full article
(This article belongs to the Special Issue Folate Absorption and Metabolism)
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14 pages, 6652 KiB  
Article
Plasma Homocysteine and Polymorphisms of Genes Involved in Folate Metabolism Correlate with DNMT1 Gene Methylation Levels
by Fabio Coppedè, Andrea Stoccoro, Pierpaola Tannorella and Lucia Migliore
Metabolites 2019, 9(12), 298; https://doi.org/10.3390/metabo9120298 - 7 Dec 2019
Cited by 9 | Viewed by 4115
Abstract
DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of DNA methylation patterns during cell division. Several human diseases are characterized by impaired DNMT1 gene methylation, but less is known about the factors that regulate DNMT1 promoter methylation levels. Dietary folates and related [...] Read more.
DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of DNA methylation patterns during cell division. Several human diseases are characterized by impaired DNMT1 gene methylation, but less is known about the factors that regulate DNMT1 promoter methylation levels. Dietary folates and related B-vitamins are essential micronutrients for DNA methylation processes, and we performed the present study to investigate the contribution of circulating folate, vitamin B12, homocysteine, and common polymorphisms in folate pathway genes to the DNMT1 gene methylation levels. We investigated DNMT1 gene methylation levels in peripheral blood DNA samples from 215 healthy individuals. All the DNA samples were genotyped for MTHFR 677C > T (rs1801133) and 1298A > C (rs1801131), MTRR 66A > G (rs1801394), MTR 2756A > G (rs1805087), SLC19A1 (RFC1) 80G > A (rs1051266), TYMS 28-bp tandem repeats (rs34743033) and 1494 6-bp insertion/deletion (indel) (rs34489327), DNMT3A -448A > G (rs1550117), and DNMT3B -149C > T (rs2424913) polymorphisms. Circulating homocysteine, folate, and vitamin B12 levels were available from 158 of the recruited individuals. We observed an inverse correlation between plasma homocysteine and DNMT1 methylation levels. Furthermore, both MTR rs1805087 and TYMS rs34743033 polymorphisms showed a statistically significant effect on DNMT1 methylation levels. The present study revealed several correlations between the folate metabolic pathway and DNMT1 promoter methylation that could be of relevance for those disorders characterized by altered DNA methylation. Full article
(This article belongs to the Special Issue Folate Absorption and Metabolism)
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Review

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12 pages, 1519 KiB  
Review
Overview of Folic Acid Supplementation Alone or in Combination with Vitamin B12 in Dairy Cattle during Periparturient Period
by Muhammad Zahoor Khan, Adnan Khan, Jianxin Xiao, Jinhuan Dou, Lei Liu and Ying Yu
Metabolites 2020, 10(6), 263; https://doi.org/10.3390/metabo10060263 - 25 Jun 2020
Cited by 15 | Viewed by 4637
Abstract
The periparturient period is the period from three weeks before calving to three weeks post-calving. This period is important in terms of health, productivity and profitability, and is fundamental to successful lactation. During this period, the animal experiences stress because of hormonal changes [...] Read more.
The periparturient period is the period from three weeks before calving to three weeks post-calving. This period is important in terms of health, productivity and profitability, and is fundamental to successful lactation. During this period, the animal experiences stress because of hormonal changes due to pregnancy and the significant rise in milk production. In addition, a negative energy balance usually occurs, because the demand for nutrients to sustain milk production increases by more than the nutrient supply during the periparturient period. The immunity of dairy cattle is suppressed around parturition, which increases their susceptibility to infections. Special care regarding nutrition can reduce the risks of metabolism and immunity depression, which dairy cattle face during the periparturient span. Folic acid is relevant in this regard because of its critical role in the metabolism to maintain lactational performance and to improve health. Being a donor of one-carbon units, folic acid has a vital role in DNA and RNA biosynthesis. Generally, the folic acid requirements of dairy cattle can be met by the microbial synthesis in the rumen; however, in special cases, such as during the periparturient period, the requirement for this vitamin strictly increases. Vitamin B12 also has a critical role in the metabolism as a coenzyme of the enzyme methionine synthase for the transfer of a methyl group from folic acid to homocysteine for the regeneration of methionine. In the current review, we highlight the issues facing periparturient dairy cattle, and relevant knowledge and practices, and point out future research directions for utilization of the associated vitamins in ruminants, especially during the periparturient period. Full article
(This article belongs to the Special Issue Folate Absorption and Metabolism)
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