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5-methyltetrahydrofolate

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https://www.readbyqxmd.com/read/27916687/a-unique-combination-of-micronutrients-rejuvenates-cognitive-performance-in-aged-mice
#1
Sam D Perez, Kristy Du, Catarina Rendeiro, Lin Wang, Qian Wu, Stanislav S Rubakhin, Rema Vazhappilly, Jeffrey H Baxter, Jonathan V Sweedler, Justin S Rhodes
It is widely believed that diet can influence the onset and severity of cognitive aging, but the optimal combination of micronutrients and molecular and cellular mechanisms remain elusive. The purpose of this study was to compare the effects of eight distinct diets, consisting of various concentrations of selected micronutrients, on learning and memory as well as markers of neuronal plasticity, and metabolic and neuro-immune status of the aged hippocampus. Eighteen-month-old male and female C57BL/6J mice were fed the diets for 16 weeks, followed by learning and memory trials on the active avoidance task...
December 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27896774/multiplex-measurement-of-serum-folate-vitamers-by-uplc-ms-ms
#2
Sarah Meadows
The implementation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to measure six folate vitamers in serum samples allows a more individual and accurate measurement than the commonly used immunoassays. In the described method, serum samples undergo solid phase extraction followed by liquid chromatography coupled with electrospray ionization tandem mass spectrometry with a run time of 3.5 min. Recovery is 95 % for the most important folate metabolite, 5-methyltetrahydrofolate (MTHF), and greater than 78 % for other minor folate forms...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27881594/hepatic-activity-and-transcription-of-betaine-homocysteine-methyltransferase-methionine-synthase-and-cystathionine-synthase-in-periparturient-dairy-cows-are-altered-to-different-extents-by-supply-of-methionine-and-choline
#3
Zheng Zhou, Timothy A Garrow, Xianwen Dong, Daniel N Luchini, Juan J Loor
BACKGROUND: Compared with choline, Met enhances milk yield and feed intake, and elicits a better immuno-metabolic status in periparturient cows. It is unknown whether hepatic activity and transcription of betaine-homocysteine methyltransferase (BHMT), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and cystathionine β-synthase (CBS) are responsive to Met and choline supply. OBJECTIVE: This study sought to characterize hepatic BHMT, MTR, and CBS transcription and activity in response to Met and choline supplementation...
November 23, 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/27860207/mediterranean-diet-gene-interactions-a-targeted-metabolomics-study-in-greek-cypriot-women
#4
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...
November 18, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27845713/novel-approaches-to-investigate-one-carbon-metabolism-and-related-b-vitamins-in-blood-pressure
#5
REVIEW
Amy McMahon, Helene McNulty, Catherine F Hughes, J J Strain, Mary Ward
Hypertension, a major risk factor for heart disease and stroke, is the world's leading cause of preventable, premature death. A common polymorphism (677C→T) in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with increased blood pressure, and there is accumulating evidence demonstrating that this phenotype can be modulated, specifically in individuals with the MTHFR 677TT genotype, by the B-vitamin riboflavin, an essential co-factor for MTHFR. The underlying mechanism that links this polymorphism, and the related gene-nutrient interaction, with hypertension is currently unknown...
November 11, 2016: Nutrients
https://www.readbyqxmd.com/read/27808252/functional-variants-of-the-5-methyltetrahydrofolate-homocysteine-methyltransferase-gene-significantly-increase-susceptibility-to-prostate-cancer-results-from-an-ethnic-han-chinese-population
#6
Yuan-Yuan Qu, Shu-Xian Zhou, Xuan Zhang, Rui Zhao, Cheng-Yuan Gu, Kun Chang, Xiao-Qun Yang, Hua-Lei Gan, Bo Dai, Hai-Liang Zhang, Guo-Hai Shi, Yao Zhu, Ding-Wei Ye, Jian-Yuan Zhao
Aberrant DNA methylation has been implicated in prostate carcinogenesis. The one-carbon metabolism pathway and related metabolites determine cellular DNA methylation and thus is thought to play a pivotal role in PCa occurrence. This study aimed to investigate the contribution of genetic variants in one-carbon metabolism genes to prostate cancer (PCa) risk and the underlying biological mechanisms. In this hospital-based case-control study of 1817 PCa cases and 2026 cancer-free controls, we genotyped six polymorphisms in three one-carbon metabolism genes and assessed their association with the risk of PCa...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27757515/high-throughput-and-simultaneous-quantitative-analysis-of-homocysteine-methionine-cycle-metabolites-and-co-factors-in-blood-plasma-and-cerebrospinal-fluid-by-isotope-dilution-lc-ms-ms
#7
Seu Ping Guiraud, Ivan Montoliu, Laeticia Da Silva, Loïc Dayon, Antonio Núñez Galindo, John Corthésy, Martin Kussmann, Francois-Pierre Martin
The methionine cycle is a key pathway contributing to the regulation of human health, with well-established involvement in cardiovascular diseases and cognitive function. Changes in one-carbon cycle metabolites have also been associated with mild cognitive decline, vascular dementia, and Alzheimer's disease. Today, there is no single analytical method to monitor both metabolites and co-factors of the methionine cycle. To address this limitation, we here report for the first time a new method for the simultaneous quantitation of 17 metabolites in the methionine cycle, which are homocysteic acid, taurine, serine, cysteine, glycine, homocysteine, riboflavin, methionine, pyridoxine, cystathionine, pyridoxamine, S-adenosylhomocysteine, S-adenosylmethionine, betaine, choline, dimethylglycine, and 5-methyltetrahydrofolic acid...
October 18, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27743887/severe-leukoencephalopathy-with-cortical-involvement-and-peripheral-neuropathy-due-to-folr1-deficiency
#8
Yu Kobayashi, Jun Tohyama, Tomoyuki Akiyama, Shinichi Magara, Hideshi Kawashima, Noriyuki Akasaka, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto
Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy...
October 12, 2016: Brain & Development
https://www.readbyqxmd.com/read/27743313/functional-characterization-of-missense-mutations-in-severe-methylenetetrahydrofolate-reductase-deficiency-using-a-human-expression-system
#9
Patricie Burda, Terttu Suormala, Dorothea Heuberger, Alexandra Schäfer, Brian Fowler, D Sean Froese, Matthias R Baumgartner
5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NADPH-dependent reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using FAD as the cofactor. Severe MTHFR deficiency is the most common inborn error of folate metabolism, resulting in hyperhomocysteinemia and homocystinuria. Approximately 70 missense mutations have been described that cause severe MTHFR deficiency, however, in most cases their mechanism of dysfunction remains unclear. Few studies have investigated mutational specific defects; most of these assessing only activity levels from a handful of mutations using heterologous expression...
October 14, 2016: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27707701/moderate-folic-acid-supplementation-and-mthfd1-synthetase-deficiency-in-mice-a-model-for-the-r653q-variant-result-in-embryonic-defects-and-abnormal-placental-development
#10
Karen E Christensen, Wenyang Hou, Renata H Bahous, Liyuan Deng, Olga V Malysheva, Erland Arning, Teodoro Bottiglieri, Marie A Caudill, Loydie A Jerome-Majewska, Rima Rozen
BACKGROUND: Moderately high folic acid intake in pregnant women has led to concerns about deleterious effects on the mother and fetus. Common polymorphisms in folate genes, such as methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) R653Q, may modulate the effects of elevated folic acid intake. OBJECTIVES: We investigated the effects of moderate folic acid supplementation on reproductive outcomes and assessed the potential interaction of the supplemented diet with MTHFD1-synthetase (Mthfd1S) deficiency in mice, which is a model for the R653Q variant...
October 5, 2016: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27692648/development-of-stable-isotope-dilution-assays-for-the-quantitation-of-intra-and-extracellular-folate-patterns-of-bifidobacterium-adolescentis
#11
Markus Kopp, Kerstin Dürr, Matthias Steigleder, Thomas Clavel, Michael Rychlik
Folate-producing bifidobacteria have been studied extensively but appropriate methods for detailed quantitation of intra- and extracellular pteroylmono- and pteroylpolyglutamate patterns are lacking. Therefore, B. adolescentis DSM 20083(T) was cultivated in folate-free medium (FFM) for 24h to develop and validate stable isotope dilution assays (SIDAs) coupled with LC-MS/MS for the determination of 5-formyltetrahydrofolic acid (5-HCO-H4folate), 10-formylfolic acid (10-HCO-PteGlu), tetrahydrofolic acid (H4folate), folic acid (PteGlu) and 5-methyltetrahydrofolic acid (5-CH3-H4folate) including its di-, tri-, and tetraglutamic vitamers (5-CH3-H4PteGlu2-4)...
October 21, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27655522/nutraceutical-approaches-to-homocysteine-lowering-in-hypertensive-subjects-at-low-cardiovascular-risk-a-multicenter-randomized-clinical-trial
#12
A Mazza, A F Cicero, E Ramazzina, S Lenti, L Schiavon, E Casiglia, G Gussoni
Although the role of homocysteine (HCys) in secondary cardiovascular prevention has been scaled down, hyper-homocysteinemia remains a risk factor for cerebrovascular events. The aim of this study was to investigate the efficacy of nutraceuticals in lowering HCys serum levels versus a conventional vitamin supplementation in hypertensive subjects at low cardiovascular risk. One-hundred and four patients (mean age 62.8±14.5 years, 63.5% males), 52 for each treatment group, were enrolled. The study recruited patients with stage 1 essential hypertension and hyper-homocysteinemia (HCys ≥15 μmol/L), without a history of cardiovascular and cerebrovascular disease...
July 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/27507672/homocysteine-metabolism-is-associated-with-cerebrospinal-fluid-levels-of-soluble-amyloid-precursor-protein-and-amyloid-beta
#13
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/27474977/the-effect-of-increasing-concentrations-of-dl-methionine-and-2-hydroxy-4-methylthio-butanoic-acid-on-hepatic-genes-controlling-methionine-regeneration-and-gluconeogenesis
#14
Qian Zhang, Sandra J Bertics, N Daniel Luchini, Heather M White
Metabolizable methionine (Met) concentrations can be increased by feeding rumen-protected dl-Met or the isopropyl ester of 2-hydroxy-4-(methylthio) butanoic acid (HMBi). Hepatic responses to increasing concentrations of metabolizable Met as a result of supplementation of different Met sources have not been comparatively examined. The objective of this experiment was to examine the regulation of key genes for Met metabolism, gluconeogenesis, and fatty acid oxidation in response to increasing concentrations of dl-Met or 2-hydroxy-4-(methylthio) butanoic acid (HMB) in bovine primary hepatocytes...
October 2016: Journal of Dairy Science
https://www.readbyqxmd.com/read/27473058/associations-between-polymorphisms-in-folate-metabolizing-genes-and-pancreatic-cancer-risk-in-japanese-subjects
#15
Haruhisa Nakao, Kenji Wakai, Norimitsu Ishii, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda, Mitsuru Mori, Masanori Nojima, Yasutoshi Kimura, Takao Endo, Masato Matsuyama, Hiroshi Ishii, Makoto Ueno, Sawako Kuruma, Naoto Egawa, Keitaro Matsuo, Satoyo Hosono, Shinichi Ohkawa, Kozue Nakamura, Akiko Tamakoshi, Mami Takahashi, Kazuaki Shimada, Takeshi Nishiyama, Shogo Kikuchi, Yingsong Lin
BACKGROUND: Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects. METHODS: Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene...
2016: BMC Gastroenterology
https://www.readbyqxmd.com/read/27431289/elevated-homocysteine-with-pseudo-homozygosity-for-mthfr677t-as-predisposing-factors-for-transient-ischemic-attacks-a-case-report
#16
A Sobczyńska-Malefora, J Cutler, Y Rahman
A 21 year old male presented with a history of intermittent, transient neurological events. A brain MRI showed an area of restricted diffusion in keeping with an infarct, and an angiogram demonstrated an intracranial stenosis in the internal carotid artery, consistent with atherosclerosis. Laboratory investigations revealed a highly elevated plasma homocysteine, with low plasma folate and 5-methyltetrahydrofolate and methionine at the lower end of the normal ranges. The homocysteine normalized following treatment with folic acid...
October 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27363740/determination-of-csf-5-methyltetrahydrofolate-in-children-and-its-application-for-defects-of-folate-transport-and-metabolism
#17
Mari Akiyama, Tomoyuki Akiyama, Kaoruko Kanamaru, Mutsuko Kuribayashi, Hiroko Tada, Tsugumi Shiokawa, Soichiro Toda, Katsumi Imai, Yu Kobayashi, Jun Tohyama, Takafumi Sakakibara, Harumi Yoshinaga, Katsuhiro Kobayashi
OBJECTIVE: To describe an assay of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF) of children, to determine reference values, and to report the clinical significance of this assay in metabolic disorders affecting folate transport and metabolism. METHODS: CSF 5MTHF was determined by high-performance liquid chromatography with fluorescent detection in pediatric patients including one with FOLR1 gene mutation and one with methylenetetrahydrofolate reductase (MTHFR) deficiency...
September 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27328863/neurological-improvement-following-intravenous-high-dose-folinic-acid-for-cerebral-folate-transporter-deficiency-caused-by-folr-1-mutation
#18
Françoise Delmelle, Beat Thöny, Philippe Clapuyt, Nenad Blau, Marie-Cécile Nassogne
BACKGROUND: Cerebral folate transporter deficiency caused by FOLR-1 mutations has been described in 2009. This condition is characterized by a 5MTHF level <5 nmol/l in the CSF, along with regression of acquisition in the second year of life, ataxia, and refractory myoclonic epilepsy. Oral or intravenous folinic acid (5-formyltetrahydrofolate) treatment has been shown to improve clinical status. CASE PRESENTATION: We present the cases of two sisters with cerebral folate transport deficiency caused by mutation in the folate receptor 1 (FOLR1) gene (MIM *136430)...
December 0: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/27325425/erratum-to-treatment-with-mefolinate-5-methyltetrahydrofolate-but-not-folic-acid-or-folinic-acid-leads-to-measurable-5-methyltetrahydrofolate-in-cerebrospinal-fluid-in-methylenetetrahydrofolate-reductase-deficiency
#19
https://www.readbyqxmd.com/read/27276031/stable-isotope-dilution-assays-for-clinical-analyses-of-folates-and-other-one-carbon-metabolites-application-to-folate-deficiency-studies
#20
Markus Kopp, Rosalie Morisset, Peter Koehler, Michael Rychlik
Folate deficiency is generally accepted as a potential direct or indirect risk factor for diseases including spina bifida, coronary heart diseases, malfunctions of the central nervous system, and cancer. The direct inclusion of folates in the methylation cycle, including the remethylation of homocysteine and regeneration of S-adenosylmethionine, underlines the importance of these vitamins and other components of one-carbon metabolism. Therefore, the aim of the present study was to develop a multiple stable isotope dilution assay (SIDA) for the respective analytes in plasma and tissue samples to allow for a closer look at the interaction between a severe folate deficiency and local folate status, as well as further interactions with circulating S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine...
2016: PloS One
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