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https://www.readbyqxmd.com/read/28842818/association-between-the-mthfr-c677t-isoform-and-structure-of-sperm-dna
#1
Dominique Cornet, Marc Cohen, Arthur Clement, Edouard Amar, Laetitia Fournols, Patrice Clement, Paul Neveux, Yves Ménézo
PURPOSE: The aim of this study is to evaluate whether the MTHFR contribution to male decreased fertility can be attributable to anomalies in sperm nucleus DNA structure in relation to defective methylation. METHODS: The presence of MTHFR C677T, contributing at most for male infertility, was determined from a venous blood sample, using real-time polymerase chain reaction (PCR). Sperm DNA fragmentation (SDF) and sperm nucleus decondensation index (SDI) measurements were performed using acridine orange and flow cytometry...
August 25, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28801717/vitamin-b6-is-essential-for-serine-de-novo-biosynthesis
#2
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...
August 11, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28760597/human-and-plasmodium-serine-hydroxymethyltransferases-differ-in-rate-limiting-steps-and-ph-dependent-substrate-inhibition-behavior
#3
Watcharee Amornwatcharapong, Somchart Maenpuen, Penchit Chitnumsub, Ubolsree Leartsakulpanich, Pimchai Chaiyen
Serine hydroxymethyltransferase (SHMT), an essential enzyme for cell growth and development, catalyzes the transfer of -CH2OH from l-serine to tetrahydrofolate (THF) to form glycine and 5,10-methylenetetrahydrofolate (MTHF) which is used for nucleotide synthesis. Insights into the ligand binding and inhibition properties of human cytosolic SHMT (hcSHMT) and Plasmodium SHMT (PvSHMT) are crucial for designing specific drugs against malaria and cancer. The results presented here revealed strong and pH-dependent THF inhibition of hcSHMT...
September 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28726126/characterization-of-a-cold-adapted-dna-photolyase-from-c-psychrerythraea-34h
#4
Sudipto Munshi, Ananthi Rajamoorthi, Robert J Stanley
The phrB gene encoding a putative cold-adapted DNA photolyase was cloned from the bacterial genomic DNA of Colwellia psychrerythraea 34H, a psychrophilic bacterium. Recombinant DNA photolyase, rCpPL, was overexpressed and purified from three different vectors. rCpPL binds its DNA substrate by flipping a cyclobutane pyrimidine dimer (CPD) into its active site and repairs CPD-containing DNA in vitro. rCpPL contains one catalytic flavin adenine dinucleotide (FAD) cofactor, but displays promiscuity in cofactor binding, in which either a flavin mononucleotide (FMN) or a methenyltetrahydrofolate (MTHF) molecule is bound as an antenna molecule and found in sub-stoichiometric amounts...
July 19, 2017: Extremophiles: Life Under Extreme Conditions
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
#5
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
#6
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
#7
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/28553478/nature-s-hydrides-rapid-reduction-of-halocarbons-by-folate-model-compounds
#8
Michael K Denk, Nicholas S Milutinović, Katherine M Marczenko, Natalie M Sadowski, Athanasios Paschos
Halocarbons R-X are reduced to hydrocarbons R-H by folate model compounds under biomimetic conditions. The reactions correspond to a halide-hydride exchange with the methylenetetrahydrofolate (MTHF) models acting as hydride donors. The MTHF models are also functional equivalents of dehalohydrogenases but, unlike these enzymes, do not require a metal cofactor. The reactions suggest that halocarbons have the potential to act as endocrinological disruptors of biochemical pathways involving MTHF. As a case in point, we observe the rapid reaction of the MTHF models with the inhalation anaesthetic halothane...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28551248/evaluating-folate-extraction-from-infant-milk-formulae-and-adult-nutritionals-enzymatic-digestion-versus-enzyme-free-heat-treatment
#9
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
#10
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...
May 2, 2017: 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
#11
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/27936107/structural-analysis-of-thymidylate-synthase-from-kaposi-s-sarcoma-associated-herpesvirus-with-the-anticancer-drug-raltitrexed
#12
Yong Mi Choi, Hyun Ku Yeo, Young Woo Park, Jae Young Lee
Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), complexes with dUMP (binary), and complexes with both dUMP and raltitrexed (ternary) were determined at 1...
2016: PloS One
https://www.readbyqxmd.com/read/27896774/multiplex-measurement-of-serum-folate-vitamers-by-uplc-ms-ms
#13
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/27863073/catalytic-transfer-hydrogenation-of-furfural-to-2-methylfuran-and-2-methyltetrahydrofuran-over-bimetallic-copper-palladium-catalysts
#14
Xin Chang, An-Feng Liu, Bo Cai, Jin-Yue Luo, Hui Pan, Yao-Bing Huang
The catalytic transfer hydrogenation of furfural to the fuel additives 2-methylfuran (2-MF) and 2-methyltetrahydrofuran (2-MTHF) was investigated over various bimetallic catalysts in the presence of the hydrogen donor 2-propanol. Of all the as-prepared catalysts, bimetallic Cu-Pd catalysts showed the highest catalytic activities towards the formation of 2-MF and 2-MTHF with a total yield of up to 83.9 % yield at 220 °C in 4 h. By modifying the Pd ratios in the Cu-Pd catalyst, 2-MF or 2-MTHF could be obtained selectively as the prevailing product...
December 8, 2016: ChemSusChem
https://www.readbyqxmd.com/read/27860207/mediterranean-diet-gene-interactions-a-targeted-metabolomics-study-in-greek-cypriot-women
#15
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/27774577/retrospective-case-control-study-of-correlation-between-mthfr-gene-and-oscc-risk-in-north-india
#16
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...
October 24, 2016: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27706773/relationship-between-genetic-polymorphisms-of-methylenetetrahydrofolate-reductase-and-breast-cancer-chemotherapy-response
#17
L Yang, X W Wang, L P Zhu, H L Wang, B Wang, T Wu, Q Zhao, D L X T JinSiHan, X Y Wang
Activity of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, is influenced by mutations in the corresponding gene, contributing to a decrease in 5,10-MTHF. Due to such polymorphisms, individuals differ in MTHFR enzyme activity and plasma folate levels. We investigated the relationship between two common MTHFR polymorphisms (C677T and A1298C) and breast cancer (BC) chemotherapy response. From February 2013 to January 2016, 148 advanced BC patients at the Center Hospital of Cangzhou were enrolled and treated with six different chemotherapy regimens...
September 23, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27556743/atmospheric-chemistry-of-tetrahydrofuran-2-methyltetrahydrofuran-and-2-5-dimethyltetrahydrofuran-kinetics-of-reactions-with-chlorine-atoms-od-radicals-and-ozone
#18
Christina Andersen, Ole John Nielsen, Freja F Østerstrøm, Stina Ausmeel, Elna J K Nilsson, Mads P Sulbaek Andersen
FTIR smog chamber techniques were used to study the kinetics of the gas-phase reactions of Cl atoms, OD radicals, and O3 with the five-membered ring-structured compounds tetrahydrofuran (C4H8O, THF), 2-methyltetrahydrofuran (CH3C4H7O, 2-MTHF), 2,5-dimethyltetrahydrofuran ((CH3)2C4H5O, 2,5-DMTHF), and furan (C4H4O). The rate coefficients determined using relative rate methods were kTHF+Cl = (1.96 ± 0.24) × 10(-10), kTHF+OD = (1.81 ± 0.27) × 10(-11), kTHF+O3 = (6.41 ± 2.90) × 10(-21), k2-MTHF+Cl = (2.65 ± 0...
September 22, 2016: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/27523499/neurometabolic-disorders-potentially-treatable-abnormalities-in-patients-with-treatment-refractory-depression-and-suicidal-behavior
#19
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
#20
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
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