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methyl tetrahydrofolate reductase

Stephanie Fryar-Williams
The Mental Health Biomarker Project (2010-2016) explored variables for psychosis in schizophrenia and schizoaffective disorder. Blood samples from 67, highly characterized symptomatic cases and 67 gender and age matched control participants were analyzed for methyl tetrahydrofolate reductase (MTHFR) 677C → T gene variants and for vitamin B6, B12 and D, folate, unbound copper, zinc cofactors for enzymes in the methylation cycle, and related catecholamine pathways. Urine samples were analyzed for indole-catecholamines, their metabolites, and oxidative-stress marker, hydroxylpyrolline-2-one (HPL)...
2016: Frontiers in Psychiatry
Q S Anders, E Stur, L P Agostini, F M Garcia, R S Reis, J A Santos, S O Mendes, L L Maia, G T Peterle, V Stange, M B Carvalho, E H Tajara, M Santos, A M A Silva-Conforti, I D Louro
The C677T and A1298C polymorphisms in methylene-tetrahydrofolate reductase (MTHFR), which regulates the release of active folate in the body, may have reduced activity. Given that folate participates in important intracellular pathways, such as nucleotide synthesis and biomolecule methylation, it seems plausible that patients with head and neck squamous cell carcinoma (HNSCC) may respond differently to radiotherapy treatments, based on genetic polymor-phisms. Therefore, this study sought to understand the role of these polymorphisms in HNSCC patient radiotherapy response...
2015: Genetics and Molecular Research: GMR
Miriam Pertegal, Francisco J Fenoy, Moisés Hernández, Jaime Mendiola, Juan L Delgado, Bárbara Bonacasa, Andrés Corno, Bernardo López, Vicente Bosch, Isabel Hernández
OBJECTIVE: To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels. DESIGN: Prospective case-control study. SETTING: University hospital. PATIENT(S): A total of 53 preeclamptic and 72 normal pregnant women...
January 2016: Fertility and Sterility
Marco Cascella, Marco Mc Cascella, Manuela Arcamone, Manuela Ma Arcamone, Emanuela Morelli, Emanuela Em Morelli, Daniela Viscardi, Daniela Dv Viscardi, Viera Russo, Viera Vr Russo, Silvia De Franciscis, Silvia Sdf De Franciscis, Andrea Belli, Andrea Ab Belli, Rosanna Accardo, Rosanna Ra Accardo, Domenico Caliendo, Domenico Dc Caliendo, Elena De Luca, Elena Edl De Luca, Barbara Di Caprio, Barbara Bdc Di Caprio, Francesco Di Sauro, Francesco Fds Di Sauro, Giovanni Giannoni, Giovanni Gg Giannoni, Carmine Iermano, Carmine Ci Iermano, Maria Maciariello, Maria Mm Maciariello, Marcella Marracino, Marcella Mm Marracino, Arturo Cuomo, Arturo Ac Cuomo
INTRODUCTION: Hyperhomocysteinemia is a known risk factor for myocardial infarction, stroke, peripheral vascular disease, and thrombosis. Elevated plasma homocysteine levels have been demonstrated in patients with recurrent episodes or a single episode of thrombosis. Here we describe the development of cardiovascular disease as a complication of a surgical intervention in a patient with colorectal cancer and hyperhomocysteinemia. CASE PRESENTATION: A 65-year-old Caucasian man complained of pain and constipation, attributed to previously diagnosed adenocarcinoma (stage IIB) of the hepatic flexure...
2015: Journal of Medical Case Reports
G Szabó, L Lazar, B Nagy, J Rigo
INTRODUCTION: One-carbon cycle is involved in two essential physiological processes: The synthesis of purins and pyrimidines required for DNA synthesis and repair. The other is the methylation with the methionine cycle. These one-carbon groups are served by the tetrahydrofolate and the S-adenosylmethionine. Deficiencies of the folate, or other abnormalities within the methionine pathway lead to elevated homocysteine levels. These disorders have been implicated in placental diseases. Earlier studies have shown that homocysteine levels are elevated by patients with severe pre-eclampsia than by healthy pregnant normotensive women...
July 2012: Pregnancy Hypertension
R Dhananjayan, T Malati, Y Rupasree, Vijay Kumar Kutala
The present work was aimed to study the association of one carbon genetic variants, hyperhomocysteinemia and oxidative stress markers, i.e., serum nitrite, plasma malondialdehyde (MDA) and glutathione (GSH) on intimal medial thickening (IMT) in patients with type 2 diabetes mellitus (T2D). A total number of 76 subjects from ACS Medical College and Hospital, Chennai, India were included in the study, i.e., Group I (n = 42) of T2D and Group II (n = 34) of age- and sex matched healthy controls. The glycated haemoglobin was measured by ion-exchange resin method; plasma homocysteine by Enzyme Linked Immunosorbant Assay method; serum nitrite (nitric oxide, NO), plasma MDA and GSH by spectrophotometric methods; the IMT by high frequency ultrasound...
July 2015: Indian Journal of Clinical Biochemistry: IJCB
Vivian Cody, Jim Pace, Ojas A Namjoshi, Aleem Gangjee
To further define the interactions that enhance the selectivity of binding and to directly compare the binding of the most potent analogue {N(6)-methyl-N(6)-(3,4,5-trifluorophenyl)pyrido[2,3-d]pyrimidine-2,4,6-triamine; compound 26} in the series of bicyclic pyrido[2,3-d]pyrimidine analogues of piritrexim (PTX) with native human (h), Pneumocystis carinii (pc) and Pneumocystis jirovecii (pj) dihydrofolate reductase (DHFR) enzymes, the crystal structures of hDHFR complexed with N(6)-methyl-N(6)-(4-isopropylphenyl)pyrido[2,3-d]pyrimidine-2,4,6-triamine (compound 22), of hDHFR complexed with compound 26 and of pcDHFR complexed with N(6)-methyl-N(6)-1-naphthylpyrido[2,3-d]pyrimidine-2,4,6-triamine (compound 24) are reported as ternary complexes with NADPH...
June 2015: Acta Crystallographica. Section F, Structural Biology Communications
Rumit Maini, Sandipan Roy Chowdhury, Larisa M Dedkova, Basab Roy, Sasha M Daskalova, Rakesh Paul, Shengxi Chen, Sidney M Hecht
In an earlier study, β³-puromycin was used for the selection of modified ribosomes, which were utilized for the incorporation of five different β-amino acids into Escherichia coli dihydrofolate reductase (DHFR). The selected ribosomes were able to incorporate structurally disparate β-amino acids into DHFR, in spite of the use of a single puromycin for the selection of the individual clones. In this study, we examine the extent to which the structure of the β³-puromycin employed for ribosome selection influences the regio- and stereochemical preferences of the modified ribosomes during protein synthesis; the mechanistic probe was a single suppressor tRNA(CUA) activated with each of four methyl-β-alanine isomers (1-4)...
June 16, 2015: Biochemistry
Johannes Bertsch, Christian Öppinger, Verena Hess, Julian D Langer, Volker Müller
UNLABELLED: The methylenetetrahydrofolate reductase (MTHFR) of acetogenic bacteria catalyzes the reduction of methylene-THF, which is highly exergonic with NADH as the reductant. Therefore, the enzyme was suggested to be involved in energy conservation by reducing ferredoxin via electron bifurcation, followed by Na(+) translocation by the Rnf complex. The enzyme was purified from Acetobacterium woodii and shown to have an unprecedented subunit composition containing the three subunits RnfC2, MetF, and MetV...
May 2015: Journal of Bacteriology
Bharath Srinivasan, Jeffrey Skolnick
Dihydrofolate reductase (DHFR) is a pivotal enzyme involved in the de novo pathway of purine synthesis, and hence, represents an attractive target to disrupt systems that require rapid DNA turnover. The enzyme acquires resistance to available drugs by various molecular mechanisms, which necessitates the continuous discovery of novel antifolates. Previously, we identified a set of novel molecules that showed binding to E. coli DHFR by means of a thermal shift without establishing whether they inhibited the enzyme...
May 2015: FEBS Journal
Leslie P Stone, P Michael Stone, Emily A Rydbom, Lucas A Stone, T Elliot Stone, Lindsey E Wilkens, Kathryn Reynolds
A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention...
November 2014: Global Advances in Health and Medicine: Improving Healthcare Outcomes Worldwide
Vinita Khot, Anvita Kale, Asmita Joshi, Preeti Chavan-Gautam, Sadhana Joshi
We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels...
2014: BioMed Research International
Brenda A Hartman, Zia Fazili, Christine M Pfeiffer, Deborah L O'Connor
It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30-36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid...
September 2014: Journal of Nutrition
Imran Patanwala, Maria J King, David A Barrett, John Rose, Ralph Jackson, Mark Hudson, Mark Philo, Jack R Dainty, Anthony J A Wright, Paul M Finglas, David E Jones
BACKGROUND: Current thinking, which is based mainly on rodent studies, is that physiologic doses of folic acid (pterylmonoglutamic acid), such as dietary vitamin folates, are biotransformed in the intestinal mucosa and transferred to the portal vein as the natural circulating plasma folate, 5-methyltetrahydrofolic acid (5-MTHF) before entering the liver and the wider systemic blood supply. OBJECTIVE: We tested the assumption that, in humans, folic acid is biotransformed (reduced and methylated) to 5-MTHF in the intestinal mucosa...
August 2014: American Journal of Clinical Nutrition
Tyler Duellman, Christopher L Warren, Jon Matsumura, Jay Yang
BACKGROUND: The natural history of abdominal aortic aneurysms (AAAs) suggests that some remain slow in growth rate whereas many develop a more accelerated growth rate and reach a threshold for intervention. We hypothesized that different mechanisms are responsible for AAAs that remain slow growing and never become actionable vs the aggressive AAAs that require intervention and may be reflected by distinct associations with genetic polymorphisms. METHODS: AAA growth rate was determined from serial imaging data in 168 control and 141 AAA patients with ultrasound or computed tomography imaging studies covering ∼5 years...
September 2014: Journal of Vascular Surgery
Nithya Narayanan, Sathnur Basappa Pushpakumar, Srikanth Givvimani, Sourav Kundu, Naira Metreveli, Dexter James, Adrienne P Bratcher, Suresh C Tyagi
Hyperhomocysteinemia (HHcy) is prevalent in patients with hypertension and is an independent risk factor for aortic pathologies. HHcy is known to cause an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), leading to the accumulation of collagen in the aorta and resulting in stiffness and development of hypertension. Although the exact mechanism of extracellular matrix (ECM) remodeling is unclear, emerging evidence implicates epigenetic regulation involving DNA methylation...
August 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wei-Qin Zhuang, Shan Yi, Markus Bill, Vanessa L Brisson, Xueyang Feng, Yujie Men, Mark E Conrad, Yinjie J Tang, Lisa Alvarez-Cohen
The acetyl-CoA "Wood-Ljungdahl" pathway couples the folate-mediated one-carbon (C1) metabolism to either CO2 reduction or acetate oxidation via acetyl-CoA. This pathway is distributed in diverse anaerobes and is used for both energy conservation and assimilation of C1 compounds. Genome annotations for all sequenced strains of Dehalococcoides mccartyi, an important bacterium involved in the bioremediation of chlorinated solvents, reveal homologous genes encoding an incomplete Wood-Ljungdahl pathway. Because this pathway lacks key enzymes for both C1 metabolism and CO2 reduction, its cellular functions remain elusive...
April 29, 2014: Proceedings of the National Academy of Sciences of the United States of America
Sandra Piras, Antonio Carta, Irene Briguglio, Paola Corona, Giuseppe Paglietti, Rosaria Luciani, Maria Paola Costi, Stefania Ferrari
Based on our previous results on the ascertained potent growth inhibition effect against a panel of 60 human tumors cell lines at National Cancer Institute of Bethesda (NCI), we have synthesized a novel series of thirty-one 2-[N-methyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines (1-31). The lead compound 1 was previously reported to be endowed with significant inhibition against hDHFR enzyme, with a Ki of 0.2 μM. Docking studies were performed on compound 1 and here reported to predict its binding conformation to human dihydrofolate reductase (hDHFR)...
March 21, 2014: European Journal of Medicinal Chemistry
Anca Botezatu, Razvan Socolov, Demetra Socolov, Iulia Virginia Iancu, Gabriela Anton
Alterations in DNA methylation patterns in several genes may lead to abnormal male sexual development and infertility. This study investigated the promoter methylation status of MTHFR and SNRPN in infertile men from Romania by quantitative methylation-specific PCR in order to investigate possible correlations with sperm abnormalities. The study groups included patients (n=27) with a median age of 31 years (range 26-41 years) as well as controls (n=11) with a median age of 30 years (range 24-37 years) recruited from couples seeking advice for infertility...
February 2014: Reproductive Biomedicine Online
Mervat Mamdooh Khorshied, Iman Abdel Mohsen Shaheen, Reham E Abu Khalil, Rania Elsayed Sheir
Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study...
January 2014: Medical Oncology
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