Thiamine Pyrophosphate
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Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1. -
One Carbon Metabolism and Its Clinical Significance
One carbon metabolism and its clinical significance Dr. Kiran Meena Department of Biochemistry Class 5 : 10-10-2019 (8:00 to 9:00 AM ) Specific Learning Objectives Describe roles of folic acid, cobalamin and S-adenosylmethionine (SAM) in transfer of one carbon units between molecules, and apply their relevance to disease states Describe synthesis of S-adenosylmethionine and its role in methylation reactions Explain how a cobalamin deficiency leads to a secondary folate deficiency Introduction Human body cannot synthesize folic acid Its also called vitamin B9 give rise to tetrahydrofolate (THF), carry one carbon groups ex. Methyl group Intestines releases mostly N5-methy-THF into blood One-carbon (1C) metabolism, mediated by folate cofactor, supports biosynthesis of purines and pyrimidines, aa homeostasis (glycine, serine and methionine) Table 14.4: DM Vasudevan’ s Textbook of Biochemistry for Medical Students 6th edition Enzyme co-factors involved in aa catabolism Involves one of three co-factors: Biotin, Tetrahydrofolate (THF) and S- adenosylmethionine (SAM) These cofactors transfer one-carbon groups in different oxidation states: 1. Biotin transfers carbon in its most oxidized state CO2, it require for catabolism and utilization of branched chain aa • Biotin responsible for carbon dioxide transfer in several carboxylase enzymes Cont-- 2. Tetrahydrofolate (THF) transfers one-carbon groups in intermediate oxidation states and as methyl groups • Tetrahydrobiopterin (BH4, THB) is a cofactor of degradation of phenylalanine • Oxidised form of THF, folate is vitamin for mammals • It converted into THF by DHF reductase 3. S-adenosylmethionine (SAM) transfers methyl groups, most reduced state of carbon THF and SAM imp in aa and nucleotide metabolism SAM used in biosynthesis of creatine, phosphatidylcholine, plasmenylcholine and epinephrine, also methylated DNA, RNA and proteins Enzymes use cobalamin as a cofactor 1. -
Recipients of Honoris Causa Degrees and of Scholarships and Awards 1999
Recipients of Honoris Causa Degrees and of Scholarships and Awards 1999 Contents HONORIS CAUSA DEGREES OF THE UNIVERSITY OF MELBOURNE- Members of the Royal Family 1 Other Distinguished Graduates 1-9 SCHOLARSHIPS AND AWARDS- The Royal Commission of the Exhibition of 1851 Science Research Scholarships 1891-1988 10 Rhodes Scholars elected for Victoria 1904- 11 Royal Society's Rutherford Scholarship Holders 1952- 11 Aitchison Travelling Scholarship (from 1950 Aitchison-Myer) Holders 1927- 12 Sir Arthur Sims Travelling Scholarship Holders 1951- 12 Rae and Edith Bennett Travelling Scholarship Holders 1979- 13 Stella Mary Langford Scholarship Holders 1979- 13 University of Melbourne Travelling Scholarships Holders 1941-1983 14 Sir William Upjohn Medal 15 University of Melbourne Silver Medals 1966-1985 15 University of Melbourne Medals (new series) 1987 - Silver 16 Gold 16 31/12/99 RECIPIENTS OF HONORIS CAUSA DEGREES AND OF SCHOLARSHIPS AND AWARDS Honoris Causa Degrees of the University of Melbourne (Where recipients have degrees from other universities this is indicated in brackets after their names.) MEMBERS OF THE ROYAL FAMILY 1868 His Royal Highness Prince Alfred Ernest Albert, Duke of Edinburgh (Edinburgh) LLD 1901 His Royal Highness Prince George Frederick Ernest Albert, Duke of York (afterwards King George V) (Cambridge) LLD 1920 His Royal Highness Edward Albert Christian George Andrew Patrick David, Prince of Wales (afterwards King Edward VIII) (Oxford) LLD 1927 His Royal Highness Prince Albert Frederick Arthur George, -
L-Carnitine, Mecobalamin and Folic Acid Tablets) TRINERVE-LC
For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only (L-Carnitine, Mecobalamin and Folic acid Tablets) TRINERVE-LC 1. Name of the medicinal product Trinerve-LC Tablets 2. Qualitative and quantitative composition Each film- coated tablets contains L-Carnitine…………………….500 mg Mecobalamin……………….1500 mcg Folic acid IP…………………..1.5mg 3. Pharmaceutical form Film- coated tablets 4. Clinical particulars 4.1 Therapeutic indications Vitamin and micronutrient supplementation in the management of chronic disease. 4.2 Posology and method of administration For oral administration only. One tablet daily or as directed by physician. 4.3 Contraindications Hypersensitivity to any constituent of the product. 4.4 Special warnings and precautions for use L-Carnitine The safety and efficacy of oral L-Carnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral L-Carnitine in patients with severely compromised renal function or in ESRD patients on dialysis may result in accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are normally excreted in the urine. Mecobalamin Should be given with caution in patients suffering from folate deficiency. The following warnings and precautions suggested with parent form – vitamin B12 The treatment of vitamin B12 deficiency can unmask the symptoms of polycythemia vera. Megaloblastic anemia is sometimes corrected by treatment with vitamin B12. But this can have very serious side effects. Don’t attempt vitamin B12 therapy without close supervision by healthcare provider. Do not take vitamin B12 if Leber’s disease, a hereditary eye disease. -
Annotation Guidelines for Experimental Procedures
Annotation Guidelines for Experimental Procedures Developed By Mohammed Alliheedi Robert Mercer Version 1 April 14th, 2018 1- Introduction and background information What is rhetorical move? A rhetorical move can be defined as a text fragment that conveys a distinct communicative goal, in other words, a sentence that implies an author’s specific purpose to readers. What are the types of rhetorical moves? There are several types of rhetorical moves. However, we are interested in 4 rhetorical moves that are common in the method section of a scientific article that follows the Introduction Methods Results and Discussion (IMRaD) structure. 1- Description of a method: It is concerned with a sentence(s) that describes experimental events (e.g., “Beads with bound proteins were washed six times (for 10 min under rotation at 4°C) with pulldown buffer and proteins harvested in SDS-sample buffer, separated by SDS-PAGE, and analyzed by autoradiography.” (Ester & Uetz, 2008)). 2- Appeal to authority: It is concerned with a sentence(s) that discusses the use of standard methods, protocols, and procedures. There are two types of this move: - A reference to a well-established “standard” method (e.g., the use of a method like “PCR” or “electrophoresis”). - A reference to a method that was previously described in the literature (e.g., “Protein was determined using fluorescamine assay [41].” (Larsen, Frandesn and Treiman, 2001)). 3- Source of materials: It is concerned with a sentence(s) that lists the source of biological materials that are used in the experiment (e.g., “All microalgal strains used in this study are available at the Elizabeth Aidar Microalgae Culture Collection, Department of Marine Biology, Federal Fluminense University, Brazil.” (Larsen, Frandesn and Treiman, 2001)). -
Nicotinamide Adenine Dinucleotide Is Transported Into Mammalian
RESEARCH ARTICLE Nicotinamide adenine dinucleotide is transported into mammalian mitochondria Antonio Davila1,2†, Ling Liu3†, Karthikeyani Chellappa1, Philip Redpath4, Eiko Nakamaru-Ogiso5, Lauren M Paolella1, Zhigang Zhang6, Marie E Migaud4,7, Joshua D Rabinowitz3, Joseph A Baur1* 1Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 2PARC, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 3Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, United States; 4School of Pharmacy, Queen’s University Belfast, Belfast, United Kingdom; 5Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; 6College of Veterinary Medicine, Northeast Agricultural University, Harbin, China; 7Mitchell Cancer Institute, University of South Alabama, Mobile, United States Abstract Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells *For correspondence: with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties [email protected] results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with †These authors contributed doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate equally to this work that NAD(H) is the imported species. -
The Influence of Vitamin B12on the Content, Distribution and in Vivo
The Influence of Vitamin B12on the Content, Distribution and in Vivo Synthesis of Thiamine Pyrophosphate, Flavin Adenine Dinucleotide and Pyridine Nucleotides in Rat Liver1 URMILA MARFATIA, D. V. REGE, H. P. TIPNIS ANDA. SREENIVASAN Department of Chemical Technology, University of Bombay, Matunga, Bombay Apart from the well-known interrelation (FAD) and pyridine nucleotides (PN), and ships among the B vitamins, there is rea to their in vivo synthesis from the corre son to believe that folie acid and vitamin sponding administered vitamins, in the rat Downloaded from Bu may influence the functioning of other liver. Data on the distribution of these vitamins as cofactors. Thus, dietary folie cofactors in liver cells of the normal rat acid has been known to determine rat are available in the works of Goethart ('52) liver stores of coenzyme A (CoA) and and Dianzani and Dianzani Mor ('57) on adenotriphosphate (ATP) (Popp and Tot TPP, of Carruthers and Suntzeff ('54) and ter, '52; Totter, '53); a decrease in liver Dianzani ('55) on pyridine nucleotides DPN is also caused by aminopterin2 (PN) and of Schneider and Hogeboom jn.nutrition.org (Strength et al., '54). The in vivo incor (Schneider, '56) on FAD. poration of nitcotinamide into pyridino- nucleotides in rat liver is affected in a EXPERIMENTAL deficiency of vitamin B«(Nadkarni et al., Young, male Wistar rats weighing ap '57). Low blood level of citrovorum factor proximately 100 gm each were used. The by guest on April 19, 2011 in the hyperthyroid, vitamin Bi2-deficient animals, housed individually in raised rat is corrected by administration of vita mesh-bottom cages, were initially depleted min B«(Pfander et al., '52). -
Chapter 7. "Coenzymes and Vitamins" Reading Assignment
Chapter 7. "Coenzymes and Vitamins" Reading Assignment: pp. 192-202, 207-208, 212-214 Problem Assignment: 3, 4, & 7 I. Introduction Many complex metabolic reactions cannot be carried out using only the chemical mechanisms available to the side-chains of the 20 standard amino acids. To perform these reactions, enzymes must rely on other chemical species known broadly as cofactors that bind to the active site and assist in the reaction mechanism. An enzyme lacking its cofactor is referred to as an apoenzyme whereas the enzyme with its cofactor is referred to as a holoenzyme. Cofactors are subdivided into essential ions and organic molecules known as coenzymes (Fig. 7.1). Essential ions, commonly metal ions, may participate in substrate binding or directly in the catalytic mechanism. Coenzymes typically act as group transfer agents, carrying electrons and chemical groups such as acyl groups, methyl groups, etc., depending on the coenzyme. Many of the coenzymes are derived from vitamins which are essential for metabolism, growth, and development. We will use this chapter to introduce all of the vitamins and coenzymes. In a few cases--NAD+, FAD, coenzyme A--the mechanisms of action will be covered. For the remainder of the water-soluble vitamins, discussion of function will be delayed until we encounter them in metabolism. We also will discuss the biochemistry of the fat-soluble vitamins here. II. Inorganic cation cofactors Many enzymes require metal cations for activity. Metal-activated enzymes require or are stimulated by cations such as K+, Ca2+, or Mg2+. Often the metal ion is not tightly bound and may even be carried into the active site attached to a substrate, as occurs in the case of kinases whose actual substrate is a magnesium-ATP complex. -
The Autobiography of Patience Loader Rozsa Archer
Utah State University DigitalCommons@USU All USU Press Publications USU Press 2006 Recollections of Past Days: The Autobiography of Patience Loader Rozsa Archer Sandra Ailey Petree Follow this and additional works at: https://digitalcommons.usu.edu/usupress_pubs Part of the United States History Commons Recommended Citation Archer, P. L., & Petree, S. A. (2006). Recollections of past days: The autobiography of Patience Loader Rozsa Archer. Logan, Utah: Utah State University Press. This Book is brought to you for free and open access by the USU Press at DigitalCommons@USU. It has been accepted for inclusion in All USU Press Publications by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. Recollections of Past Days The Autobiography of PATIENCE LOADER ROZSA ARCHER Edited by Sandra Ailey Petree Recollections of Past Days The Autobiography of Patience Loader Rozsa Archer Volume 8 Life Writings of Frontier Women A Series Edited by Maureen Ursenbach Beecher Volume 1 Winter Quarters The 1846 –1848 Life Writings of Mary Haskin Parker Richards Edited by Maurine Carr Ward Volume 2 Mormon Midwife The 1846 –1888 Diaries of Patty Bartlett Sessions Edited by Donna Toland Smart Volume 3 The History of Louisa Barnes Pratt Being the Autobiography of a Mormon Missionary Widow and Pioneer Edited by S. George Ellsworth Volume 4 Out of the Black Patch The Autobiography of Effi e Marquess Carmack Folk Musician, Artist, and Writer Edited by Noel A. Carmack and Karen Lynn Davidson Volume 5 The Personal Writings of Eliza Roxcy Snow Edited by Maureen Ursenbach Beecher Volume 6 A Widow’s Tale The 1884–1896 Diary of Helen Mar Kimball Whitney Transcribed and Edited by Charles M. -
Roles of Vitamin Metabolizing Genes in Multidrug-Resistant Plasmids of Superbugs
bioRxiv preprint doi: https://doi.org/10.1101/285403; this version posted March 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Roles of Vitamin Metabolizing Genes in Multidrug-Resistant Plasmids of Superbugs Asit Kumar Chakraborty, Genetic Engineering Laboratory, Department of Biotechnology & Biochemistry, Oriental Institute of Science & Technology, Vidyasagar University, Midnapore 721102, West Bengal, India. Abstract Superbug crisis has rocked this world with million deaths due to failure of potent antibiotics. Thousands mdr genes with hundreds of mutant isomers are generated. Small integrons and R-plasmids have combined with F'-plasmids creating a space for >10-20 of mdr genes that inactivate antibiotics in different mechanisms. Mdr genes are created to save bacteria from antibiotics because gut microbiota synthesize >20 vitamins and complex bio-molecules needed for >30000 biochemical reactions of human metabolosome. In other words, mdr gene creation is protected from both sides, intestinal luminal cells and gut bacteria in a tight symbiotic signalling system. We have proposed, to avert the crisis all vitamin metabolizing genes will be acquired in MDR- plasmids if we continue oral antibiotics therapy. Therefore, we have checked the plasmid databases and have detected thiamine, riboflavin, folate, cobalamine and biotin metabolizing enzymes in MDR plasmids. Thus vit genes may mobilise recently into MDR-plasmids and are likely essential for gut microbiota protection. Analysis found that cob and thi genes are abundant and likely very essential than other vit genes. -
Enbrace® HR DESCRIPTION: INGREDIENTS
EnBrace® HR with DeltaFolate ™ [1 NF Units] [15 mg DFE Folate] ANTI-ANEMIA PREPARATION as extrinsic/intrinsic factor concentrate plus folate. Prescription Prenatal/Vitamin Drug For Therapeutic Use Multi-phasic Capsules (30ct bottle) NDC 64661-650-30 Rx Only [DRUG] GLUTEN-FREE DESCRIPTION: EnBrace® HR is an orally administered prescription prenatal/vitamin drug for therapeutic use formulated for female macrocytic anemia patients that are in need of treatment, and are under specific direction and monitoring of vitamin B12 and vitamin B9 status by a physician. EnBrace® HR is intended for women of childbearing age who are – or desire to become, pregnant regardless of lactation status. EnBrace® HR may be prescribed for women at risk of depression as a result of folate or cobalamin deficiency - including folate-induced postpartum depression, or are at risk of folate-induced birth defects such as may be found with spina bifida and other neural tube defects (NTDs). INGREDIENTS: Cobalamin intrinsic factor complex 1 NF Units* * National Formulary Units (“NF UNITS”) equivalent to 50 mcg of active coenzyme cobalamin (as cobamamide concentrate with intrinsic factor) ALSO CONTAINS: 1 Folinic acid (B9-vitamer) 2.5 mg + 1 Control-release, citrated folic acid, DHF (B9-Provitamin) 1 mg 2 Levomefolic acid (B9 & B12- cofactor) 5.23 mg 1 6 mg DFE folate (vitamin B9) 2 9 mg DFE l-methylfolate magnesium (molar equivalent). FUNCTIONAL EXCIPIENTS: 13.6 mg FeGC as ferrous glycine cysteinate (1.5 mg 3 3,4 elemental iron ) [colorant], 25 mg ascorbates (24 mg magnesium l-ascorbate, 1 mg zinc l-ascorbate) [antioxidant], at least 23.33 mg phospholipid-omega3 complex5 [marine lipids], 500 mcg betaine (trimethylglycine) [acidifier], 1 mg magnesium l-threonate [stabilizer]. -
Coenzymes and Prosthetic Groups Nomenclature
Coenzymes and prosthetic groups Nomenclature • Cofactor: nonprotein component of enzymes • Cofactor - a co-catalyst required for enzyme activity • Coenzyme - a dissociable cofactor, usually organic • Prosthetic group - non-dissociable cofactor • Vitamin - a required micro-nutrient (organism cannot synthesize adequate quantities for normal health - may vary during life-cycle). – water soluble - not stored, generally no problem with overdose – lipid soluble - stored, often toxic with overdose. • Apoenzyme - enzyme lacking cofactor (inactive) • Holoenzyme - enzyme with cofactors (active) Vitamins are precursors of cofactors Why cofactors? Adenine Nucleotide Coenzymes All use the adenine nucleotide group solely for binding to the enzyme! • pyridine dinucleotides (NADH, NADPH) • flavin mono- and dinucleotides (FMN, FADH) • coenzyme A Nucleotide triphosphates • ATP hydrolysis – resonance stabilizes products – reactants cannot be resonance stabilized because of competition with adjacent bridging anhydrides – charge density greater on reactants than products Coenzyme A • Activation of acyl groups for transfer by nucleophilic attack • activation of the alpha- hydrogen of the acyl group for abstraction as a proton • Both these functions are mediated by the reactive -SH group on CoA, which forms thioesters Coenzyme A Nicotinic Acid/Nicotinamide Coenzymes • These coenzymes are two-electron carriers • They transfer hydride anion (H-) to and from substrates • Two important coenzymes in this class: • Nicotinamide adenine dinucleotide (NAD+) • Nicotinamide