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https://www.readbyqxmd.com/read/29666258/formate-rescues-neural-tube-defects-caused-by-mutations-in-slc25a32
#1
Jimi Kim, Yunping Lei, Jin Guo, Sung-Eun Kim, Bogdan J Wlodarczyk, Robert M Cabrera, Ying Linda Lin, Torbjorn K Nilsson, Ting Zhang, Aiguo Ren, Linlin Wang, Zhengwei Yuan, Yu-Fang Zheng, Hong-Yan Wang, Richard H Finnell
Periconceptional folic acid (FA) supplementation significantly reduces the prevalence of neural tube defects (NTDs). Unfortunately, some NTDs are FA resistant, and as such, NTDs remain a global public health concern. Previous studies have identified SLC25A32 as a mitochondrial folate transporter (MFT), which is capable of transferring tetrahydrofolate (THF) from cellular cytoplasm to the mitochondria in vitro. Herein, we show that gene trap inactivation of Slc25a32 ( Mft ) in mice induces NTDs that are folate (5-methyltetrahydrofolate, 5-mTHF) resistant yet are preventable by formate supplementation...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29596860/endothelial-dysfunction-endothelial-nitric-oxide-bioavailability-tetrahydrobiopterin-and-5-methyltetrahydrofolate-in-cardiovascular-disease-where-are-we-with-therapy
#2
REVIEW
Matthew F Yuyun, Leong L Ng, G André Ng
Homeostasis around vascular endothelium is a function of the equilibrium between the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species (ROS). Within the vascular endothelium, NO enhances vasodilatation, reduces platelet aggression and adhesion (anti-thrombotic), prevents smooth muscle proliferation, inhibits adhesion of leukocytes and expression of pro-inflammatory cytokines genes (anti-inflammatory), and counters the oxidation of low density lipoprotein (LDL) cholesterol. A shift in the equilibrium that favours NO deficiency and ROS formation leads to endothelial dysfunction and cardiovascular disease...
March 26, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29511242/the-pharmacokinetic-advantage-of-5-methyltetrahydrofolate-for-minimization-of-the-risk-for-birth-defects
#3
Steven W Bailey, June E Ayling
Despite efforts to increase folic acid (FA) intake, even within countries mandating FA fortification, there remain pregnant women with folate levels inadequate to minimize congenital disorders (e.g., of the neural tube, heart, and lip/palate). The pharmacokinetics of FA and [6S]-5-methyltetrahydrofolate (5-MTHF) were examined to find a reliable and minimal dose for rapidly rescuing folate status prior to critical periods of embryonic development. Serum total folate increased much more rapidly over the first four days in insufficient women given 7...
March 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29423831/targeted-versus-untargeted-omics-the-cafsa-story
#4
Maria Del Mar Amador, Benoit Colsch, Foudil Lamari, Claude Jardel, Farid Ichou, Agnès Rastetter, Frédéric Sedel, Fabien Jourdan, Clément Frainay, Ronald A Wevers, Emmanuel Roze, Christel Depienne, Christophe Junot, Fanny Mochel
BACKGROUND: In 2009, untargeted metabolomics led to the delineation of a new clinico-biological entity called cerebellar ataxia with elevated cerebrospinal free sialic acid, or CAFSA. In order to elucidate CAFSA, we applied sequentially targeted and untargeted omic approaches. METHODS AND RESULTS: First, we studied five of the six CAFSA patients initially described. Besides increased CSF free sialic acid concentrations, three patients presented with markedly decreased 5-methyltetrahydrofolate (5-MTHF) CSF concentrations...
February 8, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29412638/reduced-18f-folate-conjugates-as-a-new-class-of-pet-tracers-for-folate-receptor-imaging
#5
Silvan D Boss, Cristina Müller, Klaudia Siwowska, Josephine Büchel, Rafaella Schmid, Viola Groehn, Roger Schibli, Simon Mensah Ametamey
5-Methyltetrahydrofolate (5-MTHF), a reduced folate form, is the biologically active folate involved in many different metabolic processes. To date, there are no studies available in the literature on 18F-labeled 6S- and 6R-5-MTHF radiotracers for imaging FR-α-positive tissues. Therefore, the goal of this study was to synthesize four 18F-labeled 5-MTHF derivatives conjugated at either the α- or γ-carboxylic functionality of glutamate and to assess their suitability for folate receptor (FR)-targeting. Organic syntheses of the precursors and the four reference compounds, namely 6S-α, 6S-γ, 6R-α and 6R-γ-click-fluoroethyl-5-MTHF, were carried out in low to moderate overall chemical yields...
February 7, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29364915/helicobacter-pylori-moderates-the-association-between-5-mthf-concentration-and-cognitive-function-in-older-adults
#6
Andrew N Berrett, Shawn D Gale, Lance D Erickson, Bruce L Brown, Dawson W Hedges
OBJECTIVE: To explore potential interactions between folate-cycle factors and Helicobacter pylori seropositivity in the prediction of cognitive function. METHODS: We used data obtained from the 1999-2000 continuous National Health and Nutrition Examination Survey produced by the United States' Centers for Disease Control and Prevention. Using Ordinary Least Squares regression, we tested for associations between multiple folate-cycle factors, Helicobacter pylori seropositivity, and cognitive function assessed by the digit symbol coding subtest of the Wechsler Adult Intelligence Scale-III...
2018: PloS One
https://www.readbyqxmd.com/read/28801717/vitamin-b6-is-essential-for-serine-de-novo-biosynthesis
#7
Rúben J Ramos, Mia L Pras-Raves, Johan Gerrits, Maria van der Ham, Marcel Willemsen, Hubertus Prinsen, Boudewijn Burgering, Judith J Jans, Nanda M Verhoeven-Duif
Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells...
November 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28685492/role-of-intramuscular-levofolinate-administration-in%C3%A2-the%C3%A2-treatment-of-hereditary-folate-malabsorption-report-of-three-cases
#8
Emanuela Manea, Paul Gissen, Simon Pope, Simon J Heales, Spyros Batzios
Hereditary folate malabsorption is a rare autosomal recessive disorder caused by impaired active folate transport across membranes and into the central nervous system due to loss-of-function mutations in proton-coupled folate transporter (PCFT). Newborns with this condition have initially normal folate stores, but as they are unable to absorb dietary folate and use rapidly their stores because of their growth demands, symptoms appear in the early infancy. Significant neurological morbidity usually follows the initial non-specific clinical presentation and delayed initiation of treatment...
July 7, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28649192/deleterious-effects-of-chronic-folate-deficiency-in-the-ts65dn-mouse-model-of-down-syndrome
#9
Susan Helm, Morgan Blayney, Taylor Whited, Mahjabin Noroozi, Sen Lin, Semira Kern, David Green, Ahmad Salehi
Folate is an important B vitamin naturally found in the human diet and plays a critical role in methylation of nucleic acids. Indeed, abnormalities in this major epigenetic mechanism play a pivotal role in the pathogenesis of cognitive deficit and intellectual disability in humans. The most common cause of cognitive dysfunction in children is Down syndrome (DS). Since folate deficiency is very common among the pediatric population, we questioned whether chronic folate deficiency (CFD) exacerbates cognitive dysfunction in a mouse model of DS...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#10
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28551248/evaluating-folate-extraction-from-infant-milk-formulae-and-adult-nutritionals-enzymatic-digestion-versus-enzyme-free-heat-treatment
#11
COMPARATIVE STUDY
Maria V Chandra-Hioe, Martin P Bucknall, Jayashree Arcot
This study compares enzymatic treatments to release folic acid (FA) and endogenous 5-methyltetrahydrofolate (5-MTHF) from infant milk formulae with enzyme-free heat extraction. The limits of detection and quantitation of FA were 1.4ng/mL and 3.1ng/mL, respectively; 7.5ng/mL and 16.2ng/mL for 5-MTHF. Absolute mean recoveries were 85% (FA) and 95% (5-MTHF). The RSD of the within-run variability was 6% and the inter-day variability was 8%. Averaged measurements of FA and 5-MTHF in SRM-1849a were within the certified value range...
November 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28460586/supplementation-with-6s-5-methyltetrahydrofolate-or-folic-acid-equally-reduces-serum-homocysteine-concentrations-in-older-adults
#12
Ewa Sicińska, Anna Brzozowska, Wojciech Roszkowski, Paul M Finglas
Folic acid (FA) supplementation reduces the elevated serum homocysteine (Hcy) concentrations. [6 S]-5-methyltetrahydrofolate ([6 S]-5-MTHF) is an alternative to FA due to possible advantages, that is, no masking cobalamin deficiency. The study aim was to evaluate the effectiveness of [6 S]-5-MTHF in relations to FA supplementation in reducing the serum Hcy. Healthy volunteers, aged 50-65, had normal serum folate and did not use supplements with B-vitamins for 6 months. Forty subjects were divided into two groups: receiving 400 μg/d FA or the equimolar amount of [6 S]-5-MTHF...
February 2018: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/27940130/simultaneous-measurement-of-monoamine-metabolites-and-5-methyltetrahydrofolate-in-the-cerebrospinal-fluid-of-children
#13
Tomoyuki Akiyama, Yumiko Hayashi, Yoshiyuki Hanaoka, Takashi Shibata, Mari Akiyama, Kazuyuki Nakamura, Yu Tsuyusaki, Masaya Kubota, Harumi Yoshinaga, Katsuhiro Kobayashi
BACKGROUND: We describe a new method for simultaneous measurement of monoamine metabolites (3-O-methyldopa [3-OMD], 3-methoxy-4-hydroxyphenylethyleneglycol [MHPG], 5-hydroxyindoleacetic acid [5-HIAA], and homovanillic acid [HVA]) and 5-methyltetrahydrofolate (5-MTHF) and its use on cerebrospinal fluid (CSF) samples from pediatric patients. METHODS: Monoamine metabolites and 5-MTHF were measured by high-performance liquid chromatography with fluorescence detection...
February 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27860207/mediterranean-diet-gene-interactions-a-targeted-metabolomics-study-in-greek-cypriot-women
#14
Maria G Kakkoura, Kleitos Sokratous, Christiana A Demetriou, Maria A Loizidou, Giorgos Loucaides, Eleni Kakouri, Andreas Hadjisavvas, Kyriacos Kyriacou
SCOPE: A high adherence to the Mediterranean diet (MD) was previously associated with a decreased risk of breast cancer (BC) among Greek-Cypriot women. Additionally, particular polymorphisms were shown to modulate this MD-BC association. Herein, we aimed to investigate the effect of polymorphisms-MD interactions on the levels of specific metabolites that could be related to dietary adherence or enzymatic activity, which is itself modulated by polymorphisms. METHODS AND RESULTS: Greek-Cypriot women who were BC controls and had the lowest or the highest MD adherence (vegetables, fruit, legumes, fish) as assessed by principal component analysis (n = 564) were included...
April 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27774577/retrospective-case-control-study-of-correlation-between-mthfr-gene-and-oscc-risk-in-north-india
#15
Hena Naqvi, Mohammad Kaleem Ahmad, Syed Rizwan Hussain, Shalini Gupta, Mohammad Waseem, Abbas Ali Mahdi
BACKGROUND: Oral squamous cell carcinoma (OSCC) occurrence appears to be the number one among all cancers in India. Folate is a methyl donor during DNA methylation, as it provides substrate for methylenetetrahydrofolate reductase (MTHFR) to convert 5,10-MTHF to 5-MTHF and subsequently metabolizes it to methionine. The purpose of this study was to identify MTHFR C677T gene polymorphism in patients with OSCC. MATERIALS AND METHODS: A total of 350 OSCC cases and 350 healthy controls participated in this study...
July 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27523499/neurometabolic-disorders-potentially-treatable-abnormalities-in-patients-with-treatment-refractory-depression-and-suicidal-behavior
#16
Lisa A Pan, Petra Martin, Thomas Zimmer, Anna Maria Segreti, Sivan Kassiff, Brian W McKain, Cynthia A Baca, Manivel Rengasamy, Keith Hyland, Nicolette Walano, Robert Steinfeld, Marion Hughes, Steven K Dobrowolski, Michele Pasquino, Rasim Diler, James Perel, David N Finegold, David G Peters, Robert K Naviaux, David A Brent, Jerry Vockley
OBJECTIVE: Treatment-refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. At least 15% of cases of major depressive disorder remain refractory to treatment. The authors previously identified a young adult with treatment-refractory depression and multiple suicide attempts with an associated severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. Treatment with sapropterin, a tetrahydrobiopterin analogue, led to dramatic and long-lasting remission of depression...
January 1, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/27507672/homocysteine-metabolism-is-associated-with-cerebrospinal-fluid-levels-of-soluble-amyloid-precursor-protein-and-amyloid-beta
#17
Aikaterini Oikonomidi, Piotr Lewczuk, Johannes Kornhuber, Yvo Smulders, Michael Linnebank, Alexander Semmler, Julius Popp
Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. The objective of this study was to investigate the relationships between cerebral amyloid production and both blood and cerebrospinal fluid (CSF) markers of the homocysteine metabolism. We assessed CSF concentrations of soluble APPα, soluble APPβ, and amyloid β1-42 (Aβ1-42), as well as plasma levels of homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of homocysteine (Hcys-CSF), 5-methyltetrahydrofolate (5-MTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) in 59 subjects with normal cognition...
October 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27178705/csf-concentrations-of-5-methyltetrahydrofolate-in-a-cohort-of-young-children-with-autism
#18
John Shoffner, Barbara Trommer, Audrey Thurm, Cristan Farmer, William A Langley, Laura Soskey, Aldeboran N Rodriguez, Precilla D'Souza, Sarah J Spence, Keith Hyland, Susan E Swedo
OBJECTIVE: To examine the association between cerebral folate deficiency and autism, this study examined CSF 5-methyltetrahydrofolate (5-MTHF) concentrations in a group of young children with autism, investigated the natural variation in CSF 5-MTHF over time, and assessed the relationship between CSF 5-MTHF and symptoms. METHODS: CSF was collected from 67 children with a diagnosis of DSM-IV-TR autistic disorder (age, mean ± SD 43 ± 11 months), with a second CSF sample obtained 1-3 years later on 31 of these subjects (time to follow-up, 30 ± 8 months)...
June 14, 2016: Neurology
https://www.readbyqxmd.com/read/27008238/enhanced-oral-bioavailability-of-a-novel-folate-salt-comparison-with-folic-acid-and-a-calcium-folate-salt-in-a-pharmacokinetic-study-in-rats
#19
COMPARATIVE STUDY
Niccolò Miraglia, Marco Agostinetto, Davide Bianchi, Ermanno Valoti
BACKGROUND: Folates play an important role to prevent neurological disorders in embryo development and in cardiovascular diseases. Folate supplementation is suggested, particularly in females of childbearing age, for the prevention of embryonal NTDs during pregnancy. Folic acid and reduced folate ((6S)5-MTHF) are currently used in supplementation. The aim of this study was to compare the bioavailability of Quatrefolic®, a novel patented (6S)5-MTHF glucosamine salt, with (6S)5-MTHF calcium salt and folic acid in Sprague Dawley rats...
April 2016: Minerva Ginecologica
https://www.readbyqxmd.com/read/26898294/treatment-with-mefolinate-5-methyltetrahydrofolate-but-not-folic-acid-or-folinic-acid-leads-to-measurable-5-methyltetrahydrofolate-in-cerebrospinal-fluid-in-methylenetetrahydrofolate-reductase-deficiency
#20
L Knowles, A A M Morris, J H Walter
S-adenosyl methionine, which is formed from methionine, is an essential methyl donor within the central nervous system. Methionine is formed by the enzyme methionine synthase for which 5-methyltetrahydrofolate (5-MTHF) and homocysteine are substrates. Patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency cannot make 5-MTHF and have extremely low levels in the CSF. As a consequence, methylation reactions in the CNS are compromised, and this is likely to play an important role in the neurological abnormalities that occur in MTHFR deficiency...
2016: JIMD Reports
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