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Methionine Synthase Supports Tumor Tetrahydrofolate Pools
bioRxiv preprint doi: https://doi.org/10.1101/2020.09.05.284521; this version posted September 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Methionine synthase supports tumor tetrahydrofolate pools Joshua Z. Wang1,2,#, Jonathan M. Ghergurovich1,3,#, Lifeng Yang1,2, and Joshua D. Rabinowitz1,2,* 1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA 2 Department of Chemistry, Princeton University, Princeton, New Jersey, USA 3 Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA # These authors contributed equally to this work. *Corresponding author: Joshua Rabinowitz Department of Chemistry and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Rd, Princeton, NJ 08544, USA Phone: (609) 258-8985; e-mail: [email protected] Conflict of Interest Disclosure: J.D.R. is a paid advisor and stockholder in Kadmon Pharmaceuticals, L.E.A.F. Pharmaceuticals, and Rafael Pharmaceuticals; a paid consultant of Pfizer; a founder, director, and stockholder of Farber Partners and Serien Therapeutics. JDR and JMG are inventors of patents in the area of folate metabolism held by Princeton University. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.05.284521; this version posted September 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Mammalian cells require activated folates to generate nucleotides for growth and division. The most abundant circulating folate species is 5-methyl tetrahydrofolate (5-methyl- THF), which is used to synthesize methionine from homocysteine via the cobalamin-dependent enzyme methionine synthase (MTR). -
Routine Administration of Vitamin K1 Prophylaxis to the Newborn
Routine Administration of Vitamin K1 Prophylaxis to the Newborn Practice Resource for Health Care Providers July 2016 Practice Resource Guide: ROUTINE ADMINISTRATION OF VITAMIN K1 PROPHYLAXIS TO THE NEWBORN The information attached is the summary of the position statement and the recommendations from the recent CPS evidence-based guideline for routine intramuscular administration of Vitamin K1 prophylaxis to the newborn*: www.cps.ca/documents/position/administration-vitamin-K-newborns Summary Vitamin K deficiency bleeding or VKDB (formerly known as hemorrhagic disease of the newborn or HDNB) is significant bleeding which results from the newborn’s inability to sufficiently activate vitamin K-dependent coagulation factors because of a relative endogenous and exogenous deficiency of vitamin K.1 There are three types of VKDB: 1. Early onset VKDB, which appears within the first 24 hours of life, is associated with maternal medications that interfere with vitamin K metabolism. These include some anticonvulsants, cephalosporins, tuberculostatics and anticoagulants. 2. Classic VKDB appears within the first week of life, but is rarely seen after the administration of vitamin K. 3. Late VKDB appears within three to eight weeks of age and is associated with inadequate intake of vitamin K (exclusive breastfeeding without vitamin K prophylaxis) or malabsorption. The incidence of late VKDB has increased in countries that implemented oral vitamin K rather than intramuscular administration. There are three methods of Vitamin K1 administration: intramuscular, oral and intravenous. The Canadian Paediatric Society (2016)2 and the American Academy of Pediatrics (2009)3 recommend the intramuscular route of vitamin K administration. The intramuscular route of Vitamin K1 has been the preferred method in North America due to its efficacy and high compliance rate. -
Dispensing of Vitamin Products by Retail Pharmacies in South Africa: Implications for Dietitians
South African Journal of Clinical Nutrition 2016; 29(4):133–138 http://dx.doi.org/10.1080/16070658.2016.1219468 SAJCN ISSN 1607-0658 EISSN 2221-1268 Open Access article distributed under the terms of the © 2016 The Author(s) Creative Commons License [CC BY-NC 3.0] http://creativecommons.org/licenses/by-nc/3.0 RESEARCH Dispensing of vitamin products by retail pharmacies in South Africa: Implications for dietitians Ilse Trutera* and Liana Steenkampb a Department of Pharmacy, Drug Utilisation Research Unit (DURU), Nelson Mandela Metropolitan University, Port Elizabeth, South Africa b HIV & AIDS Research Unit, Nelson Mandela Metropolitan University, Port Elizabeth, South Africa *Corresponding author, email: [email protected] Objective: The objective of this study was to analyse the dispensing patterns of vitamins (Anatomical Therapeutic Chemical (ATC) group A11) over a one-year period in a group of community pharmacies in South Africa. Design and setting: A retrospective drug utilisation study was conducted on community pharmacy electronic dispensing records in South Africa recorded in 2013. Outcome measures: All products for ATC subgroup A11 were extracted and analysed. Results: A total of 164 233 vitamin products were dispensed to 84 805 patients (62.64% female patients). Males received on average 2.09 (SD = 2.63) vitamin products per year, compared to 1.84 (SD = 2.13) products for females. Ergocalciferol (A11CC01) was the most often dispensed (37.48% of all vitamin products), followed by plain Vitamin B-complex products (A11EA00) accounting for 32.77%. Ergocalciferol (vitamin D2) is only available on prescription (50 000 IU tablets or 50 000 IU/ml oily drops) in South Africa. -
Vitamin K: Double Bonds Beyond Coagulation Insights Into Differences Between Vitamin K1 and K2 in Health and Disease
International Journal of Molecular Sciences Review Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease Maurice Halder 1,†, Ploingarm Petsophonsakul 2,†, Asim Cengiz Akbulut 2,†, Angelina Pavlic 2,† , Frode Bohan 3, Eric Anderson 3, Katarzyna Maresz 4, Rafael Kramann 1 and Leon Schurgers 1,2,* 1 Division of Nephrology, RWTH Aachen University, 52074 Aachen, Germany; [email protected] (M.H.); [email protected] (R.K.) 2 Department of Biochemistry, Cardiovascular Research Institute Maastricht, 6200MD Maastricht, The Netherlands; [email protected] (P.P.); [email protected] (A.C.A.); [email protected] (A.P.) 3 NattoPharma ASA, 0283 Oslo, Norway; [email protected] (F.B.); [email protected] (E.A.) 4 International Science & Health Foundation, 30-134 Krakow, Poland; [email protected] * Correspondence: [email protected]; Tel.: +31-43-3881680; Fax: +31-43-3884159 † These authors contributed equally to this work. Received: 24 January 2019; Accepted: 16 February 2019; Published: 19 February 2019 Abstract: Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. -
An Abstract of the Thesis Of
AN ABSTRACT OF THE THESIS OF Larry Stanford Merrifield for the M.S. in Food Science (Name) (Degree) (Major) Date thesis is presented June 26, 1964 Titie FACTORS AFFECTING THE ANTIMICROBIAL ACTIVITY OF VITAMIN K 5 Abstract approved (M^jor Tp&Sfesso/) Vitamin K, 4-amino-2-methyl- 1-naphthol hydrochloride, a 5 water soluble analog of vitamin K has been shown to possess an anti- microbial activity toward many bacteria, molds, and yeast. Much of the work reported in the literature is on its use as a food preserva- tive, and it was the purpose of this study to investigate some of the factors which might affect the antimicrobial activity of vitamin K in order to add insight into its more effective use as a food preserva- tive. Pure cultures of Escherichia coli, Bacillus subtilis, Proteus vulgaris, Staphlococcus aureus, and Pseudomonas fluorescens were utilized. The effect of the method of application of vitamin K on Escherichia coli; the effect of purity of vitamin K against Escherichia coli; the bactericidal concentrations required for Escherichia coli, Bacillus subtilis, Proteus vulgaris, Staphlococcus aureus, and Pseudomonas fluorescens; the effect of an absence of oxygen; the effect of contact time with Escherichia coli; the effect of initial count/ml of Escherichia coli; and the synergistic action in combination with propylene glycol were studied. The results demonstrated that air oxidation of vitamin K was 5 necessary to obtain maximum inhibitory activity against Escherichia coli. The use of white, crystalline vitamin K synthesized in the laboratory, as compared to partially oxidized commercial prepara- tions, gave better results against Escherichia coli. -
The Vitamin B12 Coenzyme
THE VITAMIN B12 COENZYME D. DoLPHIN, A. W. JoHNSON, R. RoDRIGO and N. SHAW Department of Chemistry, University of Nottingham, U.K. INTRODUCTION In 19•58 Barker and his associatesl-3 recognized a new coenzyme which controlled the conversion of glutamate into ß-methylaspartate by Clostridium tetanomorpkim. The coenzyme was shown4 to be related to !f;-vitamin B12, i.e. contair ing an adenine nucleotide grouping in place of the 5,6-dimethyl benziminawle nucleotide of vitamin B12, although similar coenzymes con taining btnziminazole or 5,6-dimethylbenziminazole were produced by growing C. tetanomorphum in the presence of the a ppropriate base5. Other variations of the nucleotide base have been achieved using Propionibacterium arabinosum in the presence of other purines and benziminazoles6• The pres ence of;:he coenzymes in a wide variety of micro-organisms such as several species of Actinomycetes including Streptomyces olivaceus and S. griseus has been dem( mstrated by the glutamate isomerase assay7 or by isolation. I t appears thü Vitamin B12 and its analogues are always biosynthesized in the form of their coenzymes. Preliminary physical and chemical studies sug gested that in the 5,6-dimethylbenzirninazolyl cobamide coenzyme the cyanide gr )up of vitamin B12, cyanocobalamin, was replaced by an adenine nucleoside':, 5, 8 and the determination9 of the complete structure (I; R = 5'-de·)xyadenosyl) of the coenzyme by X-ray analysis revealed the existence c f an essentially covalent bond between the cobalt atom and the S'.. carbon üom of the additional 5'-deoxyadenosine group. The molecule Me CH 2• CO· NH2 In the vitamin 8 12 coenzyme R =5' - deoxyadenosyl = Me Me 539 D. -
Optimal Foods
Optimal Foods 1. Almonds: high in monounsaturated and polyunsaturated fats, with 20% of calories coming from protein and dietary fiber. Nutrients include potassium, magnesium, calcium, iron, zinc, vitamin E and an antioxidant flavonoid called amygdlin also known as laetrile. 2. Barley: Like oat bran it is high in beta-glucan fiber which helps to lower cholesterol. Nutrients include copper, magnesium, phosphorous and niacin. 3. Berries : The darker the berry the higher in anti-oxidants. Nutritionally they are an excellent source of flavonoids, especially anthocyanidins, vitamin C and both soluble and insoluble fiber. 4. Brussels Sprouts : Similar to broccoli, and a member of the cabbage family, it contains cancer fighting glucosinolates. Nutritionally it is an excellent source of vitamin C and K, the B vitamins, beta-carotene, potassium and dietary fiber. 5. Carrots: It contains the highest source of proviatamin A carotenes as well as vitamin K, biotin, vitamin C, B6, potassium, thiamine and fiber. 6. Dark Chocolate: It is rich in the flavonoids, similar to those found in berries and apples, that are more easily absorbed than in other foods. It also provides an amino acid called arginine that helps blood vessels to dilate hence regulating blood flow and helping to lower blood pressure. Choose high-quality semisweet dark chocolate with the highest cocoa content that appeals to your taste buds. 7. Dark leafy greens : Kale, arugula, spinach, mustard greens, chard, collards, etc: low calorie, anti-oxidant dense food with carotenes, vitamin C, folic acid, manganese, copper, vitamin E, copper, vitamin B6, potassium, calcium, iron and dietary fiber. Kale is a particularly excellent bioavailable source of calcium while spinach is not. -
The Potential Protective Role of Vitamin K in Diabetic Neuropathy
VITAMINS The potential protective role of vitamin K in diabetic neuropathy DILIP MEHTA Viridis Biopharma 6/10 Jogani Industrial Complex ew cases of diabetes are symptomatic pain relief (3-5). V. N. Purav Marg, Chunabhatti increasing worldwide at a rapid Mumbai 400022, India The etiopathology of peripheral pace, with the total number of neuropathy is poorly understood and many [email protected] people with diabetes was projected factors, including dietary deficiencies, may www.viridisbiopharma.com Nto rise from 171 million in 2000 to 366 million contribute to the clinical manifestation of the in 2030 – an increase of nearly 200 million in condition. Deficiency of vitamin B12 (also only three decades. There are more cases of known as cobalamin), which results in a lack diabetes in women and urban populations, of a related compound, methylcobalamin, is with diabetes in developing countries projected manifested by megaloblastic anemia, and to double in the coming years (1). has been associated with significant Based on reports from the Centers for neurological pathology, especially peripheral Disease Control and Prevention, type 2 neuropathy (6-8). Vitamin B12 is also diabetes dult onset diabetes affects associated with the onset of diabetic approximately 9.3% of the general neuropathy. In patients with diabetic population in the United States in contrast to neuropathy, vitamin B12 deficiency may be 25.9% among those 65 years or older (2). aggravated by the use of antidiabetic agents Diabetes mellitus accounts for 90% of the such as metformin (9-11). Even short-term cases of diabetes patients (3,4). treatment with metformin causes a decrease The prevalence of type 2 diabetes in serum cobalamin, folic acid and an increases with age, higher then 25 body increase in homocysteine, which leads to mass index and the presence of the disease peripheral neuropathy in patients with in family history. -
Potential Benefits of Methylcobalamin: a Review
Open Access Austin Journal of Pharmacology and Therapeutics Review Article Potential Benefits of Methylcobalamin: A Review Gupta JK* and Qureshi Shaiba Sana Department of Pharmacology, GLA University Mathura, Abstract India Methylcobalamin is an active form of vitamin B12 that helps in synthesis *Corresponding author: Jeetendra Kumar Gupta, of methionine and S-adenosylmethionine. It is required for integrity of myelin, Department of Pharmacology, Institute of Pharmaceutical neuronal function, proper red blood cell formation and DNA synthesis. The largest Research, GLA University Mathura, India group of vitamin B12 deficiency is found in typical vegetarians all over the world, which can be alleviated with its analogue Methylcobalamin. It is a beneficial Received: August 17, 2015; Accepted: September 30, drug to most of the common disorders like cardiovascular disorders, diabetes, 2015; Published: October 08, 2015 anemia, hyperhomocysteinemia and degenerative disorders. Methylcobalamin helps in the synthesis of neuronal lipids, regeneration of axonal nerves and has neuroprotective activity, which promote neurons to function in proper way and thus improves Alzheimer disease, Parkinsonism, Dementia and neuropathic syndromes. It is an approved treatment for peripheral neuropathy. Keywords: Mecobalamin; Neuropathy; Anemia; Nootropic; Dietary supplement Abbreviations essential for cell growth and replication. Sometimes the liver cannot convert cyanocobalamin into adequate amount of methylcobalamin SAMe: S-Adenosyl Methionine; ERK: Extracellular Signal- needed for proper neuronal functioning. Through enhanced Regulated Kinases; PKB: Protein Kinase B; B-globulin: Beta Globulin; methylation, it exerts its nerve cell protective effect and accelerates ENFD: Epidermal Nerve Fiber Density; DPN: Diabetic Peripheral its growth. A lot of energy is required for cyanocobalamin to remove Neuropathy; NSAIDs: Non Steroidal Anti Inflammatory Drugs; THF: its cyanide and replaces it with methyl group [3]. -
Dietary Reference Intakes (Dris): Recommended Dietary Allowances and Adequate Intakes, Vitamins Food and Nutrition Board, Institute of Medicine, National Academies
Dietary Reference Intakes (DRIs): Recommended Dietary Allowances and Adequate Intakes, Vitamins Food and Nutrition Board, Institute of Medicine, National Academies Life Stage Vitamin A Vitamin C Vitamin D Vitamin E Vitamin K Thiamin Riboflavin Niacin Vitamin B6 Folate Vitamin B12 Pantothenic Biotin Choline Group (µg/d)a (mg/d) (µg/d)b,c (mg/d) d (µg/d) (mg/d) (mg/d) (mg/d)e (mg/d) (µg/d)f (µg/d) Acid (mg/d) (µg/d) (mg/d)g Infants 0 to 6 mo 400* 40* 10 4* 2.0* 0.2* 0.3* 2* 0.1* 65* 0.4* 1.7* 5* 125* 6 to 12 mo 500* 50* 10 5* 2.5* 0.3* 0.4* 4* 0.3* 80* 0.5* 1.8* 6* 150* Children 1–3 y 300 15 15 6 30* 0.5 0.5 6 0.5 150 0.9 2* 8* 200* 4–8 y 400 25 15 7 55* 0.6 0.6 8 0.6 200 1.2 3* 12* 250* Males 9–13 y 600 45 15 11 60* 0.9 0.9 12 1.0 300 1.8 4* 20* 375* 14–18 y 900 75 15 15 75* 1.2 1.3 16 1.3 400 2.4 5* 25* 550* 19–30 y 900 90 15 15 120* 1.2 1.3 16 1.3 400 2.4 5* 30* 550* 31–50 y 900 90 15 15 120* 1.2 1.3 16 1.3 400 2.4 5* 30* 550* 51–70 y 900 90 15 15 120* 1.2 1.3 16 1.7 400 2.4h 5* 30* 550* > 70 y 900 90 20 15 120* 1.2 1.3 16 1.7 400 2.4h 5* 30* 550* Females 9–13 y 600 45 15 11 60* 0.9 0.9 12 1.0 300 1.8 4* 20* 375* 14–18 y 700 65 15 15 75* 1.0 1.0 14 1.2 400i 2.4 5* 25* 400* 19–30 y 700 75 15 15 90* 1.1 1.1 14 1.3 400i 2.4 5* 30* 425* 31–50 y 700 75 15 15 90* 1.1 1.1 14 1.3 400i 2.4 5* 30* 425* 51–70 y 700 75 15 15 90* 1.1 1.1 14 1.5 400 2.4h 5* 30* 425* > 70 y 700 75 20 15 90* 1.1 1.1 14 1.5 400 2.4h 5* 30* 425* Pregnancy 14–18 y 750 80 15 15 75* 1.4 1.4 18 1.9 600j 2.6 6* 30* 450* 19–30 y 770 85 15 15 90* 1.4 1.4 18 1.9 600j 2.6 6* 30* 450* 31–50 y 770 85 15 15 90* 1.4 1.4 18 1.9 600j 2.6 6* 30* 450* Lactation 14–18 y 1,200 115 15 19 75* 1.4 1.6 17 2.0 500 2.8 7* 35* 550* 19–30 y 1,300 120 15 19 90* 1.4 1.6 17 2.0 500 2.8 7* 35* 550* 31–50 y 1,300 120 15 19 90* 1.4 1.6 17 2.0 500 2.8 7* 35* 550* NOTE: This table (taken from the DRI reports, see www.nap.edu) presents Recommended Dietary Allowances (RDAs) in bold type and Adequate Intakes (AIs) in ordinary type followed by an asterisk (*). -
Vitamin and Mineral Requirements in Human Nutrition
P000i-00xx 3/12/05 8:54 PM Page i Vitamin and mineral requirements in human nutrition Second edition VITPR 3/12/05 16:50 Page ii WHO Library Cataloguing-in-Publication Data Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements (1998 : Bangkok, Thailand). Vitamin and mineral requirements in human nutrition : report of a joint FAO/WHO expert consultation, Bangkok, Thailand, 21–30 September 1998. 1.Vitamins — standards 2.Micronutrients — standards 3.Trace elements — standards 4.Deficiency diseases — diet therapy 5.Nutritional requirements I.Title. ISBN 92 4 154612 3 (LC/NLM Classification: QU 145) © World Health Organization and Food and Agriculture Organization of the United Nations 2004 All rights reserved. Publications of the World Health Organization can be obtained from Market- ing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permis- sion to reproduce or translate WHO publications — whether for sale or for noncommercial distri- bution — should be addressed to Publications, at the above address (fax: +41 22 791 4806; e-mail: [email protected]), or to Chief, Publishing and Multimedia Service, Information Division, Food and Agriculture Organization of the United Nations, 00100 Rome, Italy. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization and the Food and Agriculture Organization of the United Nations concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. -
The Efficacy and Safety of Intramuscular Injections Of
Original Article Singapore Med J 2011; 52(12) : 868 The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial Chiu C K, Low T H, Tey Y S, Singh V A, Shong H K ABSTRACT both singly or in combination with other forms Introduction:Chronic, nonspecific low back of treatment. pain is a difficult ailment to treat and poses an economic burden in terms of medical Keywords: methylcobalamin, nonspecific low expenses and productivity loss. The aim of back pain, vitamin B12 this study was to determine the efficacy and Singapore Med J 2011; 52(12): 868-873 safety of intramuscular metylcobalamin in the treatment of chronic nonspecific low back INTRODUCTION pain. Low back pain (LBP) affects a substantial proportion of the population. Almost every person will encounter an Methods: This was a double-blinded, episode of back pain at some point in one’s life. Back randomised, controlled experimental study. pain does not discriminate based on gender, age, race or 60 patients were assigned to either the culture. It disables the working adult from performing his methylcobalamin group or the placebo group. duties and paralyses the society due to the cost incurred The former received intramuscular injections in terms of treatment and productivity loss. In 1988, a of 500 mcg parenteral methylcobalamin in 1 survey was conducted in a semirural area in Malaysia. Department of ml solution three times a week for two weeks, Orthopaedic A total of 2,594 individuals from a multi-racial (Malay, Surgery, and the placebo group received 1 ml normal Chinese, Indian) community were interviewed.