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5-methyltetrahydrofolate

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https://www.readbyqxmd.com/read/29891918/structural-basis-for-the-regulation-of-human-5-10-methylenetetrahydrofolate-reductase-by-phosphorylation-and-s-adenosylmethionine-inhibition
#1
D Sean Froese, Jolanta Kopec, Elzbieta Rembeza, Gustavo Arruda Bezerra, Anselm Erich Oberholzer, Terttu Suormala, Seraina Lutz, Rod Chalk, Oktawia Borkowska, Matthias R Baumgartner, Wyatt W Yue
The folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 Å resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain...
June 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29878267/l-5-methyltetrahydrofolate-supplementation-increases-blood-folate-concentrations-to-a-greater-extent-than-folic-acid-supplementation-in-malaysian-women
#2
Amanda M Henderson, Rika E Aleliunas, Su Peng Loh, Geok Lin Khor, Sarah Harvey-Leeson, Melissa B Glier, David D Kitts, Tim J Green, Angela M Devlin
Background: Folic acid fortification of grains is mandated in many countries to prevent neural tube defects. Concerns regarding excessive intakes of folic acid have been raised. A synthetic analog of the circulating form of folate, l-5-methyltetrahydrofolate (l-5-MTHF), may be a potential alternative. Objective: The objective of this study was to determine the effects of folic acid or l-5-MTHF supplementation on blood folate concentrations, methyl nutrient metabolites, and DNA methylation in women living in Malaysia, where there is no mandatory fortification policy...
June 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29737822/effects-of-mthfr-a1298c-polymorphism-on-peripheral-blood-folate-concentration-in-healthy-populations-a-meta-analysis-of-observational-studies
#3
Yu Xin, Lihua Wu, Xiaolin Lu, Shaofang Shangguan, Zhen Wang, Shaoyan Chang, Jiyong Yin, Wei Piao, Ting Zhang, Li Wang
BACKGROUND AND OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) irreversibly converts 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is the main form of folate used in the body. Previous studies suggest that MTHFR polymorphism influences folate metabolism, but conflicting results are reported. We performed a meta-analysis to accurately characterize the association between MTHFR A1298C polymorphism and peripheral blood folate concentration in healthy populations...
2018: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29733806/exploiting-methionine-restriction-for-cancer-treatment
#4
REVIEW
Sushma Chaturvedi, Robert M Hoffman, Joseph R Bertino
Normal cells can synthesize sufficient methionine for growth requirements from homocysteine and 5-methyltetrahydrofolate and vitamin B12. However, many cancer-cell types require exogenous methionine for survival and therefore methionine restriction is a promising avenue for treatment. While the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) deficiency is associated with methionine dependence in cancer cells, there are other causes for tumors to require exogenous methionine. In this review we describe studies that show restricting methionine to certain cancers by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics is a promising antitumor strategy...
May 4, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29666258/formate-rescues-neural-tube-defects-caused-by-mutations-in-slc25a32
#5
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...
May 1, 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
#6
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 27, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29545912/more-severe-toxicity-of-genetic-polymorphisms-on-mthfr-activity-in-osteosarcoma-patients-treated-with-high-dose-methotrexate
#7
Lu Xie, Wei Guo, Yi Yang, Tao Ji, Jie Xu
5,10-Methylenetrahydrofolate reductase (MTHFR), a key enzyme for folate metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is located at the end of the short arm (1p36.3). Two common non-synonymous variants, the C677T (Ala222Val) and A1298C (Glu429Ala), were mainly described with decreased enzymatic activity and an alteration of intracellular folate distribution. Osteosarcomas are currently treated with high dose of methotrexate (MTX). The decreased enzyme activity of MTHFR theoretically could increase the drug action of MTX and at the same time increase toxic and side effect...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29511242/the-pharmacokinetic-advantage-of-5-methyltetrahydrofolate-for-minimization-of-the-risk-for-birth-defects
#8
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/29468149/improved-stable-isotope-dilution-assay-for-dietary-folates-using-lc-ms-ms-and-its-application-to-strawberries
#9
Lisa Striegel, Soraya Chebib, Michael E Netzel, Michael Rychlik
Folates play an important role in the human body and a deficiency of this vitamin can cause several diseases. Therefore, a reliable analytical method is crucial for the determination of folate vitamers in strawberries and other dietary folate sources. A stable isotope dilution LC-MS/MS method for analyzing folates in food was developed and validated. The folate vitamers Pteroylmonoglutamic acid, tetrahydrofolate, 5-methyltetrahydrofolate, and 5-formyltetrahydrofolate were quantified using 13 C-labeled internal standards...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29423831/targeted-versus-untargeted-omics-the-cafsa-story
#10
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-18-f-folate-conjugates-as-a-new-class-of-pet-tracers-for-folate-receptor-imaging
#11
Silvan D Boss, Cristina Müller, Klaudia Siwowska, Josephine I Büchel, Raffaella M Schmid, Viola Groehn, Roger Schibli, Simon M 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 18 F-labeled 6 S- and 6 R-5-MTHF radiotracers for imaging folate receptor (FR)-α-positive tissues. Therefore, the goal of this study was to synthesize four 18 F-labeled 5-MTHF derivatives conjugated at either the α- or γ-carboxylic functionality of glutamate and to assess their suitability for FR-targeting...
April 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29407039/a-role-for-glutamine-183-in-the-folate-oxidative-half-reaction-of-methylenetetrahydrofolate-reductase-from-escherichia-coli
#12
Chong Zuo, Amber L Jolly, Andriana P Nikolova, David I Satzer, Sirui Cao, Jeremy S Sanchez, David P Ballou, Elizabeth E Trimmer
The flavoprotein methylenetetrahydrofolate reductase (MTHFR) from Escherichia coli catalyzes a ping-pong reaction with NADH and 5,10-methylenetetrahydrofolate (CH2 -H4 folate) to produce NAD+ and 5-methyltetrahydrofolate (CH3 -H4 folate). This work focuses on the function of the invariant, active-site aminoacyl residue Gln183. X-ray structures of the enzyme complexes Ered (wild-type)•NADH and Eox (Glu28Gln)•CH3 -H4 folate indicate that Gln183 makes key hydrogen-bonding interactions with both NADH and folate in their respective half-reactions, suggesting roles in binding each substrate...
March 15, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29364915/helicobacter-pylori-moderates-the-association-between-5-mthf-concentration-and-cognitive-function-in-older-adults
#13
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/29344585/hereditary-folate-malabsorption-due-to-a-mutation-in-the-external-gate-of-the-proton-coupled-folate-transporter-slc46a1
#14
Srinivas Aluri, Rongbao Zhao, Charlotte Lubout, Susanna M I Goorden, Andras Fiser, I David Goldman
Hereditary folate malabsorption (HFM) is an autosomal recessive disorder characterized by impaired intestinal folate absorption and impaired folate transport across the choroid plexus due to loss of function of the proton-coupled folate transporter (PCFT-SLC46A1). We report a novel mutation, causing HFM, affecting a residue located in the 11th transmembrane helix within the external gate. The mutant N411K-PCFT was stable, trafficked to the cell membrane, and had sufficient residual activity to characterize the transport defect and the structural requirements at this site for gate function...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29321350/neuro-fuzzy-model-of-homocysteine-metabolism
#15
Shaik Mohammad Naushad, Akella Radha Rama Devi, Sriraman Nivetha, Ganapathy Lakshmitha, Alex Balraj Stanley, Tajamul Hussain, Vijay Kumar Kutala
In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and genetic variables in influencing homocysteinemetabolism and investigated the influence of life style modulations in controlling homocysteine levels. Total plasma homocysteine levels were measured in fasting samples using reverse phase HPLC. Multiple linear regression (MLR) and neuro-fuzzy models were developed...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29243819/novel-dietary-supplement-association-reduces-symptoms-in-endometriosis-patients
#16
Pietro G Signorile, Rosa Viceconte, Alfonso Baldi
Endometriosis is characterized by disabling symptoms that afflict young women with severe physical discomfort, difficulty in relationship life, and infertility; however, the currently available therapeutic strategies are unsatisfactory. Goal of this research was to identify a new combination of natural active ingredients that, administered as dietary supplements, could have the effect of reducing inflammatory response in endometriosis patients, decreasing the symptoms the disease produces and its harmful effects on affected organs...
August 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29090559/-liver-metabonomics-of-acute-gouty-arthritis-treated-by-diosocorea-nipponica
#17
Shu-Min Liu, Ning Zhang, Dong-Hua Yu, Yu Wang, Qi Zhou, Fang Lu
To explore the prevention and protection effect of Diosocorea nipponica (DNM)) on acute gouty arthritis (AGA) rats based on liver metabonomics, and find potential biomarkers and related pathways. AGA model rats were induced by monosodium urate crystal suspension. UPLC-TOF-MS coupled with pattern recognition technique was employed to find out the potential biomarkers and related metabolic pathways. Eleven common potential biomarkers were identified. Among the potential intervention targets in normal rats given by DNM, 4 biomarkers were up-regulated, and the other 4 targets were down regulated...
May 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29058482/identification-and-determination-of-naturally-occurring-folates-in-grains-of-rice-oryza-sativa-l-by-uplc-ms-ms-analysis
#18
Kaliyaperumal Ashokkumar, Paramasivam Sivakumar, Muthukrishnan Saradhadevi
The genetic potential and biofortification of India-grown rice with bioavailable folate has not been studied yet. The objectives of this study were to determine the folates concentration in four cultivars of rice through UPLC-MS/MS. Total folate concentration in rice cultivars ranged from 11.0 to 51 μg/100 g with a mean of 26.0 μg/100 g. Among the four rice cultivars, the pigmented grain cultivar Nootripathu possesses two-fold rich sources of total folates than the other three non-pigmented grain cultivars...
October 23, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28991880/folic-acid-impairs-the-uptake-of-5-methyltetrahydrofolate-in-human-umbilical-vascular-endothelial-cells
#19
Desiree Smith, Jacqueline Hornstra, Monica Rocha, Gerrit Jansen, Yehuda Assaraf, Inbal Lasry, Henk Blom, Yvo M Smulders
BACKGROUND: Adequate folate status supports endothelial structure and function. Folic acid (FA), an oxidized synthetic folate, which is present in the plasma of patients consuming fortified food or FA supplements, may impair cellular uptake of physiological, reduced folates. We studied the effect of FA on uptake of the dominant circulatory folate, 5-methyltetrahydrofolate (5MTHF) in endothelial cells. METHODS AND RESULTS: For short-term effects of FA, primary human umbilical vein endothelial cells (HUVECs) were maintained in growth medium containing 200 nM 5MTHF and preincubated with 20 nM FA 10 minutes before the 5MTHF uptake assessment...
October 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28984387/gene-expression-differences-in-the-methionine-remethylation-and-transsulphuration-pathways-under-methionine-restriction-and-recovery-with-d-l-methionine-or-d-l-hmtba-in-meat-type-chickens
#20
S E Aggrey, F González-Cerón, R Rekaya, Y Mercier
This study examined the molecular mechanisms of methionine pathways in meat-type chickens where birds were provided with a diet deficient in methionine from 3 to 5 weeks of age. The birds on the deficient diet were then provided with a diet supplemented with either D,L-methionine or D,L-HMTBA from 5 to 7 weeks. The diet of the control birds was supplemented with L-methionine from hatch till 7 weeks of age. We studied the mRNA expression of methionine adenosyltransferase 1, alpha, methionine adenosyltransferase 1, beta, 5-methyltetrahydrofolate-homocysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine S-methyltransferase, glycine N-methyltransferase, S-adenosyl-L-homocysteine hydrolase and cystathionine beta synthase genes in the liver, duodenum, Pectoralis (P...
February 2018: Journal of Animal Physiology and Animal Nutrition
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