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https://www.readbyqxmd.com/read/29679304/analytic-approaches-for-the-treatment-of-hyperhomocysteinemia-and-its-impact-on-vascular-disease
#1
REVIEW
Soo-Sang Kang, Robert S Rosenson
Homocysteine is an intermediary metabolite in the methionine cycle. Accumulation of homocysteine is caused either by mutation of relevant genes or by nutritional depletion of related vitamin(s). This review covers the historical background of hyperhomocysteinemia in which indispensable subjects in relation to underlying pathophysiological processes are discussed with the view of metabolism and genetics of folate and methionine cycles. This review emphasizes the unique role of homocysteine that is clearly distinct from other risk factors, particularly cholesterol in the development of vascular disease...
April 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29666258/formate-rescues-neural-tube-defects-caused-by-mutations-in-slc25a32
#2
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
#3
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/29511242/the-pharmacokinetic-advantage-of-5-methyltetrahydrofolate-for-minimization-of-the-risk-for-birth-defects
#4
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
#5
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
#6
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/29372624/selective-hydrogenolysis-of-furfural-derivative-2-methyltetrahydrofuran-into-pentanediol-acetate-and-pentanol-acetate-over-pd-c-and-sc-otf-3-cocatalytic-system
#7
Kun Zhang, Xing-Long Li, Shi-Yan Chen, Hua-Jian Xu, Jin Deng, Yao Fu
It is of great significance to convert platform molecules and their derivatives into high value-added alcohols, which have multitudinous applications. This study concerns systematic conversion of 2-methyltetrahydrofuran (MTHF), which is obtained from furfural, into 1-pentanol acetate (PA) and 1,4-pentanediol acetate (PDA). Reaction parameters, such as the Lewis acid species, reaction temperature, and hydrogen pressure, were investigated in detail. 1 H NMR spectroscopy and reaction dynamics study were also conducted to help clarify the reaction mechanism...
February 22, 2018: ChemSusChem
https://www.readbyqxmd.com/read/29364915/helicobacter-pylori-moderates-the-association-between-5-mthf-concentration-and-cognitive-function-in-older-adults
#8
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/29363957/integrative-co-2-capture-and-hydrogenation-to-methanol-with-reusable-catalyst-and-amine-toward-a-carbon-neutral-methanol-economy
#9
Sayan Kar, Raktim Sen, Alain Goeppert, G K Surya Prakash
Herein we report an efficient and recyclable system for tandem CO2 capture and hydrogenation to methanol. After capture in an aqueous amine solution, CO2 is hydrogenated in high yield to CH3 OH (>90%) in a biphasic 2-MTHF/water system, which also allows for easy separation and recycling of the amine and catalyst for multiple reaction cycles. Between cycles, the produced methanol can be conveniently removed in vacuo. Employing this strategy, catalyst Ru-MACHO-BH and polyamine PEHA were recycled three times with 87% of the methanol producibility of the first cycle retained, along with 95% of catalyst activity after four cycles...
February 7, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29054081/reductive-dehalogenation-of-ddt-with-folate-models-formation-of-the-ddt-metabolite-spectrum-under-biomimetic-conditions
#10
Michael K Denk, Nicholas S Milutinović
The insecticide DDT is an omnipresent environmental contaminant and an ongoing toxicological concern. The recent discovery that methylenetetrahydrofolate (MTHF) models are capable of reducing a range of halocarbons to hydrocarbons under biomimetic conditions has prompted us to investigate the possible role of MTHF in the metabolism of DDT. We now report that the reaction of MTHF models with DDT produces no less than five known in vivo metabolites of DDT, namely DDD, DDE, DDMU, DBP, and DDM. The capability of the MTHF models to produce the full spectrum of known DDT dehalogenation products is strong evidence that the mechanistically obscure metabolism of DDT may involve MTHF...
January 2018: Chemosphere
https://www.readbyqxmd.com/read/28842818/association-between-the-mthfr-c677t-isoform-and-structure-of-sperm-dna
#11
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...
October 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28801717/vitamin-b6-is-essential-for-serine-de-novo-biosynthesis
#12
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/28760597/human-and-plasmodium-serine-hydroxymethyltransferases-differ-in-rate-limiting-steps-and-ph-dependent-substrate-inhibition-behavior
#13
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 -CH2 OH 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
#14
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...
September 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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