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| riboflavin |
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| CHEBI:17015 |
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| D-Ribitol in which the hydroxy group at position 5 is substituted by a 7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl moiety. It is a nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables, but the richest natural source is yeast. The free form occurs only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as flavin mononucleotide and flavin-adenine dinucleotide. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:45214, CHEBI:15044, CHEBI:27299, CHEBI:8843, CHEBI:529204
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| ChemicalBook:CB4383318, eMolecules:711592, Selleckchem:Riboflavin-Vitamin-B2, ZINC000002036848 |
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Molfile
XML
SDF
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more structures >>
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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__821257128963044__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__821257128963044__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:17015","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__821257128963044__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"821257128963044","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__821257128963044__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol RBF - 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| Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in energy metabolism, cellular respiration, and antibody production, as well as normal growth and development. The coenzymes are also required for the metabolism of niacin, vitamin B6, and folate. Riboflavin is prescribed to treat corneal thinning, and taken orally, may reduce the incidence of migraine headaches in adults.
Riboflavin deficiency is rare and is usually accompanied by deficiencies of other vitamins and nutrients. It may be prevented or treated by oral supplements or by injections. As a water-soluble vitamin, any riboflavin consumed in excess of nutritional requirements is not stored; it is either not absorbed or is absorbed and quickly excreted in urine, causing the urine to have a bright yellow tint. Natural sources of riboflavin include meat, fish and fowl, eggs, dairy products, green vegetables, mushrooms, and almonds. Some countries require its addition to grains.
In its purified, solid form, it is a water-soluble yellow-orange crystalline powder. In addition to its function as a vitamin, it is used as a food coloring agent. Biosynthesis takes place in bacteria, fungi and plants, but not animals. Industrial synthesis of riboflavin was initially achieved using a chemical process, but current commercial manufacturing relies on fermentation methods using strains of fungi and genetically modified bacteria. |
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Read full article at Wikipedia
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InChI=1S/C17H20N4O6/c1- 7-3-9-10(4-8(7)2)21(5-11(23)14(25)12(24)6-22)15-13(18-9)16(26)20-17(27)19-15/h3-4,11-12,14,22-25H,5-6H2,1-2H3,(H,20,26,27)/t11-,12+,14-/m0/s1 |
| AUNGANRZJHBGPY-SCRDCRAPSA-N |
| CC1=C(C)C=C2N(C[C@H](O)[C@H](O)[C@H](O)CO)C3=NC(=O)NC(=O)C3=NC2=C1 |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Mangifera indica
(NCBI:txid29780)
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See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
Geigy Scientific Tables, 8th Rev edition, pp. 165-177. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.
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Homo sapiens
(NCBI:txid9606)
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Found in
saliva
(UBERON:0001836).
See:
Sugimoto et al. (2013) Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles.
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Homo sapiens
(NCBI:txid9606)
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Found in
urine
(BTO:0001419).
See:
Geigy Scientific Tables, 8th Rev edition, pp. 130. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp. Basel, Switzerland c1981-1992.
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Homo sapiens
(NCBI:txid9606)
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Found in
cerebrospinal fluid
(UBERON:0001359).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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antioxidant
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
cofactor
An organic molecule or ion (usually a metal ion) that is required by an enzyme for its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
food colouring
A food additive that imparts colour to food. In European countries, E-numbers for permitted food colours are from E 100 to E 199, divided into yellows (E 100-109), oranges (E 110-119), reds (E 120-129), blues and violets (E 130-139), greens (E 140-149), browns and blacks (E 150-159), and others (E 160-199).
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
human urinary metabolite
Any metabolite (endogenous or exogenous) found in human urine samples.
fundamental metabolite
Any metabolite produced by all living cells.
water-soluble vitamin (role)
Any vitamin that dissolves in water and readily absorbed into tissues for immediate use. Unlike the fat-soluble vitamins, they are not stored in the body and need to be replenished regularly in the diet and will rarely accumulate to toxic levels since they are quickly excreted from the body via urine.
(via B vitamin )
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photosensitizing agent
A chemical compound that can be excited by light of a specific wavelength and subsequently transfer energy to a chosen reactant. This is commonly molecular oxygen within a cancer tissue, which is converted to (highly rective) singlet state oxygen. This rapidly reacts with any nearby biomolecules, ultimately killing the cancer cells.
food colouring
A food additive that imparts colour to food. In European countries, E-numbers for permitted food colours are from E 100 to E 199, divided into yellows (E 100-109), oranges (E 110-119), reds (E 120-129), blues and violets (E 130-139), greens (E 140-149), browns and blacks (E 150-159), and others (E 160-199).
anti-inflammatory agent
Any compound that has anti-inflammatory effects.
nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
(via B vitamin )
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View more via ChEBI Ontology
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1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)-D-ribitol
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riboflavin
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WHO MedNet
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riboflavina
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WHO MedNet
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riboflavine
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WHO MedNet
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riboflavinum
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WHO MedNet
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1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
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NIST Chemistry WebBook
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5-deoxy-5-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)-D-ribitol
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ChEBI
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6,7-dimethyl-9-D-ribitylisoalloxazine
 Note: (2004-06-30) Uses obsolete isoalloxazine skeletal numbering system. |
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ChemIDplus
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7,8-dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4(3H,10H)-dione
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ChEBI
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7,8-dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)isoalloxazine
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ChemIDplus
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7,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4(3H,10H)-dione
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IUPAC
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7,8-dimethyl-10-ribitylisoalloxazine
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KEGG COMPOUND
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E101
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ChEBI
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lactoflavin
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KEGG COMPOUND
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riboflavin (vit B2)
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DrugCentral
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Vitamin B2
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KEGG COMPOUND
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vitamin B2
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ChEBI
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vitamin G
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DrugBank
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vitasan B2
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ChemIDplus
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Aqua-Flave
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ChemIDplus
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Beflavin
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ChemIDplus
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Beflavine
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ChemIDplus
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Bisulase
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KEGG DRUG
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Dermadram
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ChemIDplus
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Fiboflavin
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ChemIDplus
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Flavaxin
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ChemIDplus
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Flavin Bb
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ChemIDplus
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Flaxain
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ChemIDplus
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Hyflavin
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ChemIDplus
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2834
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DrugCentral
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431981
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ChemSpider
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C00001552
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KNApSAcK
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C00255
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KEGG COMPOUND
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D00050
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KEGG DRUG
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DB00140
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DrugBank
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FDB012160
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FooDB
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HMDB0000244
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HMDB
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LSM-4084
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LINCS
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RBF
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PDBeChem
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Riboflavin
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Wikipedia
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RIBOFLAVIN
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MetaCyc
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US2807611
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Patent
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US2876169
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Patent
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| View more database links |
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83-88-5
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CAS Registry Number
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KEGG COMPOUND
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83-88-5
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CAS Registry Number
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NIST Chemistry WebBook
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83-88-5
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CAS Registry Number
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ChemIDplus
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97831
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Reaxys Registry Number
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Reaxys
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Plantone D, Pardini M, Rinaldi G (2021)
Riboflavin in Neurological Diseases: A Narrative Review.
Clinical drug investigation 41, 513-527 [PubMed:33886098]
[show Abstract]
Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors and is required for numerous flavoprotein-catalysed reactions. Riboflavin has important antioxidant properties, essential for correct cell functioning. It is required for the conversion of oxidised glutathione to the reduced form and for the mitochondrial respiratory chain as complexes I and II contain flavoprotein reductases and electron transferring flavoproteins. Riboflavin deficiency has been demonstrated to impair the oxidative state of the body, especially in relation to lipid peroxidation status, in both animal and human studies. In the nervous system, riboflavin is essential for the synthesis of myelin and its deficiency can determine the disruption of myelin lamellae. The inherited condition of restricted riboflavin absorption and utilisation, reported in about 10-15% of world population, warrants further investigation in relation to its association with the main neurodegenerative diseases. Several successful trials testing riboflavin for migraine prevention were performed, and this drug is currently classified as a Level B medication for migraine according to the American Academy of Neurology evidence-based rating, with evidence supporting its efficacy. Brown-Vialetto-Van Laere syndrome and Fazio-Londe diseases are now renamed as "riboflavin transporter deficiency" because these are autosomal recessive diseases caused by mutations of SLC52A2 and SLC52A3 genes that encode riboflavin transporters. High doses of riboflavin represent the mainstay of the therapy of these diseases and high doses of riboflavin should be rapidly started as soon as the diagnosis is suspected and continued lifelong. Remarkably, some mitochondrial diseases respond to supplementation with riboflavin. These include multiple acyl-CoA-dehydrogenase deficiency (which is caused by ETFDH gene mutations in the majority of the cases, or mutations in the ETFA and ETFB genes in a minority), mutations of ACAD9 gene, mutations of AIFM1 gene, mutations of the NDUFV1 and NDUFV2 genes. Therapeutic riboflavin administration has been tried in other neurological diseases, including stroke, multiple sclerosis, Friedreich's ataxia and Parkinson's disease. Unfortunately, the design of these clinical trials was not uniform, not allowing to accurately assess the real effects of this molecule on the disease course. In this review we analyse the properties of riboflavin and its possible effects on the pathogenesis of different neurological diseases, and we will review the current indications of this vitamin as a therapeutic intervention in neurology. | Pandey G, Joshi A (2021)
Riboflavin as an internal marker for spoilage and adulteration detection in milk.
Food chemistry 357, 129742 [PubMed:33892358]
[show Abstract]
Milk is a common consumable in daily life due to its nutritional values. Ensuring milk's integrity and authenticity is a prime task for researchers and food industries by providing solutions to prevent spoilage and adulteration. We present a robust and reliable optical method to ensure milk quality through its constituent riboflavin as an internal biomarker. Riboflavin is a widely present constituent in several food matrices. This research demonstrates the characteristic fluorescence of riboflavin for checking spoilage and urea adulteration in real-time. The proposed method can even detect and quantify high urea adulteration levels up to 80 mM (i.e., eight times permissible standard value) with a LOD value of 9.3 mM. The linearity (0-80 mM) and high R2 value (0.98, 0.93) of riboflavin's fluorescence in pure and milk solutions, respectively present this strategy closely associated with fate of milk samples in terms of spoilage and adulteration. Thus, this optical method of riboflavin biosensing in real-time is intuitive and conclusive for determining milk quality. | Zhao G, Dong F, Lao X, Zheng H (2021)
Strategies to Increase the Production of Biosynthetic Riboflavin.
Molecular biotechnology 63, 909-918 [PubMed:34156642]
[show Abstract]
Riboflavin is widely regarded as an essential nutrient that is involved in biological oxidation in vivo. In addition to preventing and treating acyl-CoA dehydrogenase deficiency in patients with keratitis, stomatitis, and glossitis, riboflavin is also closely related to the treatment of radiation mucositis and cardiovascular disease. Chemical synthesis has been the dominant method for producing riboflavin for approximately 50 years. Nevertheless, due to the intricate synthesis process, relatively high cost, and high risk of pollution, alternative methods of chemical syntheses, such as the fermentation method, began to develop and eventually became the main methods for producing riboflavin. At present, there are three types of strains used in industrial riboflavin production: Ashbya gossypii, Candida famata, and Bacillus subtilis. Additionally, many recent studies have been conducted on Escherichia coli and Lactobacillus. Fermentation increases the yield of riboflavin using genetic engineering technology to modify and induce riboflavin production in the strain, as well as to regulate the metabolic flux of the purine pathway and pentose phosphate pathway (PP pathway), thereby optimizing the culture process. This article briefly introduces recent progress in the fermentation of riboflavin. | Averianova LA, Balabanova LA, Son OM, Podvolotskaya AB, Tekutyeva LA (2020)
Production of Vitamin B2 (Riboflavin) by Microorganisms: An Overview.
Frontiers in bioengineering and biotechnology 8, 570828 [PubMed:33304888]
[show Abstract]
Riboflavin is a crucial micronutrient that is a precursor to coenzymes flavin mononucleotide and flavin adenine dinucleotide, and it is required for biochemical reactions in all living cells. For decades, one of the most important applications of riboflavin has been its global use as an animal and human nutritional supplement. Being well-informed of the latest research on riboflavin production via the fermentation process is necessary for the development of new and improved microbial strains using biotechnology and metabolic engineering techniques to increase vitamin B2 yield. In this review, we describe well-known industrial microbial producers, namely, Ashbya gossypii, Bacillus subtilis, and Candida spp. and summarize their biosynthetic pathway optimizations through genetic and metabolic engineering, combined with random chemical mutagenesis and rational medium components to increase riboflavin production. | Ahn H, Lee GS (2020)
Riboflavin, vitamin B2, attenuates NLRP3, NLRC4, AIM2, and non-canonical inflammasomes by the inhibition of caspase-1 activity.
Scientific reports 10, 19091 [PubMed:33154451]
[show Abstract]
Riboflavin is commonly taken as a nutritional supplement, and it converts to coenzymes during the process of energy production from carbohydrates, fats, and proteins. Although riboflavin is considered to be an anti-inflammatory vitamin because of its antioxidant properties, the effects of riboflavin on inflammasome have been not reported. Inflammasome, a cytosolic surveillance protein complex, leads to the activation of caspase-1, cytokine maturation, and pyroptosis. In the present study, riboflavin attenuated the indicators of NLRP3 inflammasome activation in macrophages, such as the maturation and secretion of interleukin (IL)-1β, IL-18, and caspase-1; the formation of Asc pyroptosome; and the cleavage of gasdermin D. In addition, the oral and peritoneal administration of riboflavin inhibited the peritoneal production of IL-1β and IL-18 in a mouse model. Mechanistically, riboflavin prevented mitochondrial perturbations, such as mitochondrial ROS production and mitochondrial DNA release, which trigger the NLRP3 inflammasome assembly. Riboflavin was further confirmed to disrupt the activity of caspase-1, and it also inhibited the AIM2, NLRC4, and non-canonical inflammasomes. Therefore, riboflavin has both an antioxidant effect and an anti-inflammasome property that regulates the inflammatory response. | Chang CY, Yan X, Crnovcic I, Annaval T, Chang C, Nocek B, Rudolf JD, Yang D, Hindra, Babnigg G, Joachimiak A, Phillips GN, Shen B (2018)
Resistance to Enediyne Antitumor Antibiotics by Sequestration.
Cell chemical biology 25, 1075-1085.e4 [PubMed:29937405]
[show Abstract]
The enediynes, microbial natural products with extraordinary cytotoxicities, have been translated into clinical drugs. Two self-resistance mechanisms are known in the enediyne producers-apoproteins for the nine-membered enediynes and self-sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share a similar β barrel-like structure, bind TNMs with nanomolar KD values, and confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes. Mechanisms of self-resistance in producers serve as models to predict and combat future drug resistance in clinical settings. Enediyne-based chemotherapies should now consider the fact that the human microbiome harbors genes encoding enediyne resistance. | Endres S, Granzin J, Circolone F, Stadler A, Krauss U, Drepper T, Svensson V, Knieps-Grünhagen E, Wirtz A, Cousin A, Tielen P, Willbold D, Jaeger KE, Batra-Safferling R (2015)
Structure and function of a short LOV protein from the marine phototrophic bacterium Dinoroseobacter shibae.
BMC microbiology 15, 30 [PubMed:25887755]
[show Abstract]
BackgroundLight, oxygen, voltage (LOV) domains are widely distributed in plants, algae, fungi, bacteria, and represent the photo-responsive domains of various blue-light photoreceptor proteins. Their photocycle involves the blue-light triggered adduct formation between the C(4a) atom of a non-covalently bound flavin chromophore and the sulfur atom of a conserved cysteine in the LOV sensor domain. LOV proteins show considerable variation in the structure of N- and C-terminal elements which flank the LOV core domain, as well as in the lifetime of the adduct state.ResultsHere, we report the photochemical, structural and functional characterization of DsLOV, a LOV protein from the photoheterotrophic marine α-proteobacterium Dinoroseobacter shibae which exhibits an average adduct state lifetime of 9.6 s at 20°C, and thus represents the fastest reverting bacterial LOV protein reported so far. Mutational analysis in D. shibae revealed a unique role of DsLOV in controlling the induction of photopigment synthesis in the absence of blue-light. The dark state crystal structure of DsLOV determined at 1.5 Å resolution reveals a conserved core domain with an extended N-terminal cap. The dimer interface in the crystal structure forms a unique network of hydrogen bonds involving residues of the N-terminus and the β-scaffold of the core domain. The structure of photoexcited DsLOV suggests increased flexibility in the N-cap region and a significant shift in the Cα backbone of β strands in the N- and C-terminal ends of the LOV core domain.ConclusionsThe results presented here cover the characterization of the unusual short LOV protein DsLOV from Dinoroseobacter shibae including its regulatory function, extremely fast dark recovery and an N-terminus mediated dimer interface. Due to its unique photophysical, structural and regulatory properties, DsLOV might thus serve as an alternative model system for studying light perception by LOV proteins and physiological responses in bacteria. | Serer MI, Bonomi HR, Guimarães BG, Rossi RC, Goldbaum FA, Klinke S (2014)
Crystallographic and kinetic study of riboflavin synthase from Brucella abortus, a chemotherapeutic target with an enhanced intrinsic flexibility.
Acta crystallographica. Section D, Biological crystallography 70, 1419-1434 [PubMed:24816110]
[show Abstract]
Riboflavin synthase (RS) catalyzes the last step of riboflavin biosynthesis in microorganisms and plants, which corresponds to the dismutation of two molecules of 6,7-dimethyl-8-ribityllumazine to yield one molecule of riboflavin and one molecule of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. Owing to the absence of this enzyme in animals and the fact that most pathogenic bacteria show a strict dependence on riboflavin biosynthesis, RS has been proposed as a potential target for antimicrobial drug development. Eubacterial, fungal and plant RSs assemble as homotrimers lacking C3 symmetry. Each monomer can bind two substrate molecules, yet there is only one active site for the whole enzyme, which is located at the interface between two neighbouring chains. This work reports the crystallographic structure of RS from the pathogenic bacterium Brucella abortus (the aetiological agent of the disease brucellosis) in its apo form, in complex with riboflavin and in complex with two different product analogues, being the first time that the structure of an intact RS trimer with bound ligands has been solved. These crystal models support the hypothesis of enhanced flexibility in the particle and also highlight the role of the ligands in assembling the unique active site. Kinetic and binding studies were also performed to complement these findings. The structural and biochemical information generated may be useful for the rational design of novel RS inhibitors with antimicrobial activity. | Ravi G, Venkatesh YP (2014)
Recognition of riboflavin and the capsular polysaccharide of Haemophilus influenzae type b by antibodies generated to the haptenic epitope D-ribitol.
Glycoconjugate journal 31, 247-258 [PubMed:24643482]
[show Abstract]
D-Ribitol, a five-carbon sugar alcohol, is an important metabolite in the pentose phosphate pathway; it is an integral part of riboflavin (vitamin B2) and cell wall polysaccharides in most Gram-positive and a few Gram-negative bacteria. Antibodies specific to D-ribitol were generated in New Zealand white rabbits by using reductively aminated D-ribose-BSA conjugate as the immunogen. MALDI-TOF and amino group analyses of ribitol-BSA conjugate following 120 h reaction showed ~27-30 mol of ribitol conjugated per mole BSA. The presence of sugar alcohol in the conjugates was also confirmed by an increase in molecular mass and a positive periodic acid-Schiff staining in SDS-PAGE. Caprylic acid precipitation of rabbit serum followed by hapten affinity chromatography on ribitol-KLH-Sepharose CL-6B resulted in pure ribitol-specific antibodies (~45-50 μg/mL). The affinity constant of ribitol antibodies was found to be 2.9 × 10(7) M(-1) by non-competitive ELISA. Ribitol antibodies showed 100% specificity towards ribitol, ~800% cross-reactivity towards riboflavin, 10-15% cross-reactivity with sorbitol, xylitol and mannitol, and 5-7% cross-reactivity with L-arabinitol and meso-erythritol. The specificity of antibody to ribitol was further confirmed by its low cross-reactivity (0.4%) with lumichrome. Antibodies to D-ribitol recognized the purified capsular polysaccharide of Haemophilus influenzae type b, which could be specifically inhibited by ribitol. In conclusion, antibodies specific to D-ribitol have been generated and characterized, which have potential applications in the detection of free riboflavin and ribitol in biological samples, as well as identification of cell-surface macromolecules containing ribitol. | Ravi G, Venkatesh YP (2014)
Recognition of flavin mononucleotide, Haemophilus influenzae type b and its capsular polysaccharide vaccines by antibodies specific to D-ribitol-5-phosphate.
Glycoconjugate journal 31, 573-585 [PubMed:25108762]
[show Abstract]
D-Ribitol-5-phosphate (Rbt-5-P) is an important metabolite in the pentose phosphate pathway and an integral part of bacterial cell wall polysaccharides, specifically as polyribosyl ribitol phosphate (PRP) in Haemophilus influenzae type b (Hib). The major objective of this study was to investigate whether an antibody specific to Rbt-5-P can recognize the PRP of Hib. D-Ribose-5-phosphate was reacted with proteins in the presence of sodium cyanoborohydride to obtain Rbt-5-P epitopes; 120 h reaction resulted in conjugation of ~30 and ~17 moles of Rbt-5-P/mole of BSA and OVA, respectively, based on decrease in amino groups, MALDI-TOF analyses, an increase in apparent molecular weight (SDS-PAGE) and glycoprotein staining. Immunization of rabbits with Rbt-5-P-BSA conjugate generated antibodies to Rbt-5-P as demonstrated by dot immunoblot and non-competitive ELISA. Homogeneous Rbt-5-P-specific antibody was purified from Rbt-5-P-BSA antiserum subjected to caprylic acid precipitation followed by hapten-affinity chromatography; its affinity constant is 7.1 × 10(8) M(-1). Rbt-5-P antibody showed 100 % specificity to Rbt-5-P, ~230 %, 10 % and 3.4 % cross-reactivity to FMN, riboflavin and FAD, respectively; the antibody showed ~4 % cross-reactivity to D-ribitol and <3 % to other sugars/sugar alcohols. Rbt-5-P-specific antibody recognized Hib conjugate vaccines containing PRP which was inhibited specifically by Rbt-5-P, and also detected Hib cell-surface capsular polysaccharides by immunofluorescence. In conclusion, Rbt-5-P-protein conjugate used as an immunogen elicited antibodies binding to an epitope also present in PRP and Hib bacteria. Rbt-5-P-specific antibody has potential applications in the detection and quantification of free/bound Rbt-5-P and FMN as well as immunological recognition of Hib bacteria and its capsular polysaccharide. | Rivera-Cancel G, Ko WH, Tomchick DR, Correa F, Gardner KH (2014)
Full-length structure of a monomeric histidine kinase reveals basis for sensory regulation.
Proceedings of the National Academy of Sciences of the United States of America 111, 17839-17844 [PubMed:25468971]
[show Abstract]
Although histidine kinases (HKs) are critical sensors of external stimuli in prokaryotes, the mechanisms by which their sensor domains control enzymatic activity remain unclear. Here, we report the full-length structure of a blue light-activated HK from Erythrobacter litoralis HTCC2594 (EL346) and the results of biochemical and biophysical studies that explain how it is activated by light. Contrary to the standard view that signaling occurs within HK dimers, EL346 functions as a monomer. Its structure reveals that the light-oxygen-voltage (LOV) sensor domain both controls kinase activity and prevents dimerization by binding one side of a dimerization/histidine phosphotransfer-like (DHpL) domain. The DHpL domain also contacts the catalytic/ATP-binding (CA) domain, keeping EL346 in an inhibited conformation in the dark. Upon light stimulation, interdomain interactions weaken to facilitate activation. Our data suggest that the LOV domain controls kinase activity by affecting the stability of the DHpL/CA interface, releasing the CA domain from an inhibited conformation upon photoactivation. We suggest parallels between EL346 and dimeric HKs, with sensor-induced movements in the DHp similarly remodeling the DHp/CA interface as part of activation. | Staudt H, Hoesl MG, Dreuw A, Serdjukow S, Oesterhelt D, Budisa N, Wachtveitl J, Grininger M (2013)
Directed manipulation of a flavoprotein photocycle.
Angewandte Chemie (International ed. in English) 52, 8463-8466 [PubMed:23818044] | Roux A, Xu Y, Heilier JF, Olivier MF, Ezan E, Tabet JC, Junot C (2012)
Annotation of the human adult urinary metabolome and metabolite identification using ultra high performance liquid chromatography coupled to a linear quadrupole ion trap-Orbitrap mass spectrometer.
Analytical chemistry 84, 6429-6437 [PubMed:22770225]
[show Abstract]
Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory. They were also grouped, thanks to software tools, and annotated using public databases. Metabolite identification was achieved using two complementary approaches: (i) formal identification by matching chromatographic retention times, mass spectra, and also product ion spectra (if required) of metabolites to be characterized in biological data sets to those of reference compounds and (ii) putative identification from biological data thanks to MS/MS experiments for metabolites not available in our chemical library. By these means, 384 metabolites corresponding to 1484 annotated features (659 in negative ion mode and 825 in positive ion mode) were characterized in human urine samples. Of these metabolites, 192 and 66 were formally and putatively identified, respectively, and 54 are reported in human urine for the first time. These lists of features could be used by other laboratories to annotate their ESI-MS metabolomics data sets. | Sato Y, Shimizu S, Ohtaki A, Noguchi K, Miyatake H, Dohmae N, Sasaki S, Odaka M, Yohda M (2010)
Crystal structures of the lumazine protein from Photobacterium kishitanii in complexes with the authentic chromophore, 6,7-dimethyl- 8-(1'-D-ribityl) lumazine, and its analogues, riboflavin and flavin mononucleotide, at high resolution.
Journal of bacteriology 192, 127-133 [PubMed:19854891]
[show Abstract]
Lumazine protein (LumP) is a fluorescent accessory protein having 6,7-dimethyl-8-(1'-d-ribityl) lumazine (DMRL) as its authentic chromophore. It modulates the emission of bacterial luciferase to shorter wavelengths with increasing luminous strength. To obtain structural information on the native structure as well as the interaction with bacterial luciferase, we have determined the crystal structures of LumP from Photobacterium kishitanii in complexes with DMRL and its analogues, riboflavin (RBF) and flavin mononucleotide (FMN), at resolutions of 2.00, 1.42, and 2.00 A. LumP consists of two beta barrels that have nearly identical folds, the N-terminal and C-terminal barrels. The structures of LumP in complex with all of the chromophores studied are all essentially identical, except around the chromophores. In all of the structures, the chromophore is tethered to the narrow cavity via many hydrogen bonds in the N-terminal domain. These are absent in the C-terminal domain. Hydrogen bonding in LumP-FMN is decreased in comparison with that in LumP-RBF because the phosphate moiety of FMN protrudes out of the narrow cavity. In LumP-DMRL, the side chain of Gln65 is close to the ring system, and a new water molecule that stabilizes the ligand is observed near Ser48. Therefore, DMRL packs more tightly in the ligand-binding site than RBF or FMN. A docking simulation of bacterial luciferase and LumP suggests that the chromophore is located close enough for direct energy transfer to occur. Moreover, the surface potentials around the ligand-binding sites of LumP and bacterial luciferase exhibit complementary charge distributions, which would have a significant effect on the interaction between LumP and luciferase. | Serganov A, Huang L, Patel DJ (2009)
Coenzyme recognition and gene regulation by a flavin mononucleotide riboswitch.
Nature 458, 233-237 [PubMed:19169240]
[show Abstract]
The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches, also known as RFN elements, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B(2)) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg(2+)-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains. | Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM (2009)
Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.
Nature 457, 910-914 [PubMed:19212411]
[show Abstract]
Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity. | Juárez O, Nilges MJ, Gillespie P, Cotton J, Barquera B (2008)
Riboflavin is an active redox cofactor in the Na+-pumping NADH: quinone oxidoreductase (Na+-NQR) from Vibrio cholerae.
The Journal of biological chemistry 283, 33162-33167 [PubMed:18832377]
[show Abstract]
Here we present new evidence that riboflavin is present as one of four flavins in Na+-NQR. In particular, we present conclusive evidence that the source of the neutral radical is not one of the FMNs and that riboflavin is the center that gives rise to the neutral flavosemiquinone. The riboflavin is a bona fide redox cofactor and is likely to be the last redox carrier of the enzyme, from which electrons are donated to quinone. We have constructed a double mutant that lacks both covalently bound FMN cofactors (NqrB-T236Y/NqrC-T225Y) and have studied this mutant together with the two single mutants (NqrB-T236Y and NqrC-T225Y) and a mutant that lacks the noncovalently bound FAD in NqrF (NqrF-S246A). The double mutant contains riboflavin and FAD in a 0.6:1 ratio, as the only flavins in the enzyme; noncovalently bound flavins were detected. In the oxidized form, the double mutant exhibits an EPR signal consistent with a neutral flavosemiquinone radical, which is abolished on reduction of the enzyme. The same radical can be observed in the FAD deletion mutant. Furthermore, when the oxidized enzyme reacts with ubiquinol (the reduced form of the usual electron acceptor) in a process that reverses the physiological direction of the electron flow, a single kinetic phase is observed. The kinetic difference spectrum of this process is consistent with one-electron reduction of a neutral flavosemiquinone. The presence of riboflavin in the role of a redox cofactor is thus far unique to Na+-NQR. | Grininger M, Zeth K, Oesterhelt D (2006)
Dodecins: a family of lumichrome binding proteins.
Journal of molecular biology 357, 842-857 [PubMed:16460756]
[show Abstract]
Dodecin is a small dodecameric flavoprotein from Halobacterium salinarum that contains two flavins stacked between two tryptophan residues to form an aromatic tetrade. The functional properties of heterologously expressed dodecin were investigated by fluorescence spectroscopy, which allowed the determination of dissociation constants for a number of protein-ligand complexes. The values obtained were in the nanomolar to micromolar range and correlate positively with the ligand size. These data were supplemented by X-ray crystal structures of the apododecin and holocomplexes with lumichrome, lumiflavin, riboflavin and FMN at resolutions between 1.55 to 1.95 A to unravel a gating mechanism as the structural basis for the preferential binding of the small ligands lumichrome and lumiflavin. The detailed analysis of the dodecin manifold for preferential binding of lumichrome and lumiflavin provides insight on a subatom level into a protein's strategy to gain selectivity for low molecular mass compounds by steric restrictions rather than specific interactions. Investigations on the ligand composition of a wild-type dodecin crystal (1.32 A resolution) support conclusions of functional and structural investigations on heterologously expressed dodecin, and strongly suggest that lumichrome, a molecule associated with the flavin metabolism, is a ligand of dodecin in vivo. Studies on mutant protein and a Halorhodospira halophila homologue spread the idea of a lumichrome binding system as a possible "waste"-trapping device, widely distributed in prokaryotes. | Verdrengh M, Tarkowski A (2005)
Riboflavin in innate and acquired immune responses.
Inflammation research : official journal of the European Histamine Research Society ... [et al.] 54, 390-393 [PubMed:16273338]
[show Abstract]
Objective and designRiboflavin, also known as vitamin B2, is a micronutrient with a key role in maintaining human health. It has also been shown to enhance host resistance to bacterial infections in mice. The aim of this study was to assess the role of vitamin B2 treatment in inflammatory conditions.Subjects and methodsThree models of inflammatory states were assessed. One of them encompasses neutrophil mediated but T cell/macrophage independent cutaneous inflammation. Another one is delayed type hypersensitivity reaction (DTH), a T cell/macrophage dependent but neutrophil independent inflammatory response. The third one is collagen- induced arthritis, having components from both of the above described reactions. Mice were treated with vitamin B2, administered by peritoneal injections, throughout the course of the experiments.ResultsThe granulocyte dependent reaction to olive oil was significantly reduced in vitamin B2 treated mice. In contrast, DTH reactivity and collagen II arthritis were not affected by the treatment.ConclusionRiboflavin administration affects neutrophil migration but does not alter acquired immune responsiveness. | Meining W, Eberhardt S, Bacher A, Ladenstein R (2003)
The structure of the N-terminal domain of riboflavin synthase in complex with riboflavin at 2.6A resolution.
Journal of molecular biology 331, 1053-1063 [PubMed:12927541]
[show Abstract]
Riboflavin synthase of Escherichia coli is a homotrimer with a molecular mass of 70 kDa. The enzyme catalyzes the dismutation of 6,7-dimethyl-8-(1'-D-ribityl)-lumazine, affording riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. The N-terminal segment (residues 1-87) and the C-terminal segment (residues 98-187) form beta-barrels with similar fold and a high degree of sequence similarity. A recombinant peptide comprising amino acid residues 1-97 forms a dimer, which binds riboflavin with high affinity. Here, we report the structure of this construct in complex with riboflavin at 2.6A resolution. It is demonstrated that the complex can serve as a model for ligand-binding in the native enzyme. The structure and riboflavin-binding mode is in excellent agreement with structural information obtained from the native enzyme from Escherichia coli and riboflavin synthase from Schizosaccharomyces pombe. The implications for the binding specificity and the regiospecificity of the catalyzed reaction are discussed. | Zhou X, Huang C, Hong J, Yao S (2003)
[Nested case-control study on riboflavin levels in blood and urine and the risk of lung cancer].
Wei sheng yan jiu = Journal of hygiene research 32, 597-8, 601 [PubMed:14963913]
[show Abstract]
The present study is designed to explore the relationship between the riboflavin levels in blood and urine and the risk of lung cancer among miners in Yunnan Tin Corporation(YTC) by means of nested case-control design. Cases were patients with lung cancer newly diagnosed from 1992 to 1995. For each case, 2 controls were randomly matched with occupational exposure history, age, the time of collecting blood or urine samples. The indexes for evaluating the riboflavin nutritional status were erythrocyte glutathione reductase activation coefficient (EGR-AC) and the ratio of riboflavin and creatinine in urine. When analyzed as either the continuous or the rank variables, the odds ratios(ORs) used to estimate the relative risk of lung cancer have no statistical significance(P > 0.05) after adjusting the confusing factors. No association of riboflavin indexes in blood and urine with the lung cancer risk among YTC miners were observed in the present study. | Gerhardt S, Haase I, Steinbacher S, Kaiser JT, Cushman M, Bacher A, Huber R, Fischer M (2002)
The structural basis of riboflavin binding to Schizosaccharomyces pombe 6,7-dimethyl-8-ribityllumazine synthase.
Journal of molecular biology 318, 1317-1329 [PubMed:12083520]
[show Abstract]
Riboflavin is an essential cofactor in all organisms. Its direct biosynthetic precursor, 6,7-dimethyl-8-ribityllumazine, is synthesised by the enzyme 6,7-dimethyl-8-ribityllumazine synthase. Recently, we have found that the enzyme from Schizosaccharomyces pombe binds riboflavin, the final product of the pathway with a relatively high affinity with a KD of 1.2 microM. Here, we report on the crystal structure of lumazine synthase from S. pombe with bound riboflavin and compare the binding mode with those of the substrate analogue inhibitor 5-nitro-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione and of the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine. In all complexes the pyrimidinedione moieties of each respective ligand bind in a very similar orientation. Binding of riboflavin additionally involves a stacking interaction of the dimethylbenzene moiety with the side-chain of His94, a highly conserved residue in all lumazine synthases. The enzyme from Bacillus subtilis showed a KD of at least 1 mM whereas the very homologous enzyme from Saccharomyces cerevisiae had a comparable KD of 3.9 microM. Structural comparison of the S. cerevisiae, the S. pombe, and the mutant enzymes suggests that fine tuning of affinity is achieved by influencing this stacking interaction. | Mathew JL, Kabi BC, Rath B (2002)
Anti-oxidant vitamins and steroid responsive nephrotic syndrome in Indian children.
Journal of paediatrics and child health 38, 450-437 [PubMed:12354259]
[show Abstract]
ObjectiveIn recent years, it has been proposed that nephrotic syndrome is a consequence of an imbalance between oxidant and anti-oxidant activity. In the present study, the levels of micronutrient anti-oxidant vitamins (vitamin E, vitamin C, carotene and riboflavin) in Indian children with steroid responsive nephrotic syndrome were investigated. Their levels were measured during the acute proteinuric phase of the disease, as well as during clinical recovery (remission), in order to understand the possible role of nutritionally modifiable anti-oxidants in the aetiopathogenesis of the disease.MethodsThe study was a hospital based, prospective cohort study. Serum and erythrocyte vitamin E, leucocyte vitamin C, serum carotene, erythrocyte riboflavin activity and serum malonyldialdehyde (MDA) levels were measured in 30 consecutive cases of children with nephrotic syndrome (International Study of Kidney Diseases in Children (ISKDC) criteria) during the proteinuric phase of the disease and at 4 weeks after remission was induced by steroid therapy. The same biochemical parameters were measured in healthy siblings (controls) of the 30 patients.ResultsMean vitamin E (serum and erythrocyte), vitamin C and carotene were significantly lower during the proteinuric phase of the disease, and there was decreased erythrocyte riboflavin activity. There was significant elevation in the serum level of MDA during this phase. In addition, all these parameters tended to improve during remission, although complete normalization did not occur.ConclusionThese vitamins were active in performing their anti-oxidant function, as indicated by significant depression in their levels during the acute (proteinuric) phase, followed by partial recovery during remission. It may be concluded that steroid responsive nephrotic syndrome in children is associated with oxidative stress. | Mikalunas V, Fitzgerald K, Rubin H, McCarthy R, Craig RM (2001)
Abnormal vitamin levels in patients receiving home total parenteral nutrition.
Journal of clinical gastroenterology 33, 393-396 [PubMed:11606856]
[show Abstract]
The administration of multivitamins to patients receiving home parenteral nutrition (HPN) was decreased from once daily to three times weekly during the parenteral multivitamin shortage in 1997. Blood vitamin levels were measured to examine whether the decrement in the infused vitamins affected the levels. Six patients with normal renal and liver function, receiving HPN for 6 months to 10 years, were studied 6 months after the institution of 10 mL of multivitamins thrice weekly. Two patients with renal insufficiency who required hemodialysis and HPN were also studied. Multivitamin administration was eliminated in one patient and was reduced to once weekly when elevated pyridoxine levels were found in association with possible neurotoxicity. Five of the six patients with normal renal function had low serum ascorbic acid levels. Serum riboflavin levels were found to be low in one patient, serum pyridoxine was low in one, serum retinoids were low in three, and serum niacin was low in one. There were no clinically obvious untoward effects caused by the vitamin deficiencies. Each of the dialysis patients had elevated serum pyridoxine levels and had some neurologic disturbance (peripheral neuropathy, involuntary movements). The serum pyridoxine levels fell to normal in each after the cessation or decrease of the multivitamin preparation. Ascorbic acid levels were low in one patient and fell into abnormally low levels in the other when the parenteral multivitamins were reduced, but they corrected with the separate administration of intravenous vitamin C. In conclusion, the reduced administration of multivitamins in 1997 resulted in diminished ascorbic acid levels in seven of eight patients receiving total parenteral nutrition. Less often, low levels of retinoids, niacin, pyridoxine, and riboflavin were seen. Patients with chronic renal failure receiving HPN with multivitamins may develop elevated pyridoxine levels, which might result in neurologic sequelae. | Truffault V, Coles M, Diercks T, Abelmann K, Eberhardt S, Lüttgen H, Bacher A, Kessler H (2001)
The solution structure of the N-terminal domain of riboflavin synthase.
Journal of molecular biology 309, 949-960 [PubMed:11399071]
[show Abstract]
The structure of the amino-terminal domain of Escherichia coli riboflavin synthase (RiSy) has been determined by NMR spectroscopy with riboflavin as a bound ligand. RiSy is functional as a 75 kDa homotrimer, each subunit of which consists of two domains which share very similar sequences and structures. The N-terminal domain (RiSy-N; 97 residues) forms a 20 kDa homodimer in solution which binds riboflavin with high affinity. The structure features a six-stranded antiparallel beta-barrel with a Greek-key fold, both ends of which are closed by an alpha-helix. One riboflavin molecule is bound per monomer in a site at one end of the barrel which is comprised of elements of both monomers. The structure and ligand binding are similar to that of the FAD binding domains of ferrodoxin reductase family proteins. The structure provides insights into the structure of the whole enzyme, the organisation of the functional trimer and the mechanism of riboflavin synthesis. C48 from the N-terminal domain is identified as the free cysteine implicated in a nucleophilic role in the synthesis mechanism, while H102 from the C-terminal domains is also likely to play a key role. Both are invariant in all known riboflavin synthase sequences. | Rao PN, Levine E, Myers MO, Prakash V, Watson J, Stolier A, Kopicko JJ, Kissinger P, Raj SG, Raj MH (1999)
Elevation of serum riboflavin carrier protein in breast cancer.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 8, 985-990 [PubMed:10566553]
[show Abstract]
Presently available tumor markers have had a limited clinical impact. Riboflavin carrier protein (RCP) is an estrogen inducible protein that occupies a key position in riboflavin metabolism. Because other vitamin carrier proteins (VCP) have been shown to be overexpressed in patients with malignant disease, we evaluated serum RCP levels in patients with adenocarcinoma of the breast. In this prospective blinded study, patients with breast cancer, benign breast disease, and healthy controls were analyzed for RCP levels. Using a highly sensitive RIA, we observed that serum RCP levels were significantly elevated in women with breast cancer (n = 52) as compared with control subjects [n = 50; 6.06 +/- 7.27 ng/ml versus 0.70 +/- 0.19 ng/ml (mean +/- SD), respectively; P < 0.0001]. A serum RCP level of > or = 1.0 ng/ml was highly predictive of the presence of breast cancer, detecting 88% of tumors in stages I-II and 100% of tumors in stages III-IV. Overall, this RCP assay has a sensitivity of 92.3%, a specificity of 88%, a positive predictive value of 88.9%, and a negative predictive value of 91.7%. These results show increased serum levels of RCP in breast adenocarcinoma patients and suggest that RCP levels may be useful as a new marker for breast cancer. The positive predictive value in early-stage breast cancer suggests that the RCP assay may be a useful adjunct to present screening technology. | Walsh MA, McCarthy A, O'Farrell PA, McArdle P, Cunningham PD, Mayhew SG, Higgins TM (1998)
X-ray crystal structure of the Desulfovibrio vulgaris (Hildenborough) apoflavodoxin-riboflavin complex.
European journal of biochemistry 258, 362-371 [PubMed:9874201]
[show Abstract]
The apoprotein of flavodoxin from Desulfovibrio vulgaris forms a complex with riboflavin. The ability to bind riboflavin distinguishes this flavodoxin from other short-chain flavodoxins which require the phosphate of FMN for flavin binding. The redox potential of the semiquinone/hydroquinone couple of the bound riboflavin is 180 mV less negative than the corresponding complex with FMN. To elucidate the binding of riboflavin, the complex has been crystallized and the crystal structure solved by molecular replacement using native flavodoxin as a search model to a resolution of 0.183 nm. Compared to the FMN complex, the hydrogen-bonding network at the isoalloxazine sub-site of the riboflavin complex is severely disrupted by movement of the loop residues Ser58-Ile64 (60-loop) which contact the isoalloxazine by over 0.35 nm, and by a small displacement of the isoalloxazine moiety. The 60-loop movement away from the flavin increases the solvent exposure of the flavin-binding site. The conformation of the site at which 5'-phosphate of FMN normally binds is similar in the two complexes, but in the riboflavin complex a sulphate or phosphate ion from the crystallization buffer occupies the space. This causes small structural perturbations in the phosphate-binding site. The flexibility of the 60-loop in D. vulgaris flavodoxin appears to be a contributing factor to the binding of riboflavin by the apoprotein, and a feature that distinguishes the protein from other 'short chain' flavodoxins. In the absence of the terminal phosphate group, free movement at the 5'-OH group of the ribityl chain can occur. Thus, the 5'-phosphate of FMN secures the cofactor at the binding site and positions it optimally. The structural changes which occur in the 60-loop in the riboflavin complex probably account for most of the positive shift that is observed in the midpoint potential of the semiquinone/hydroquinone couple of the riboflavin complex compared to that of the FMN complex. | Booth CK, Clark T, Fenn A (1998)
Folic acid, riboflavin, thiamine, and vitamin B-6 status of a group of first-time blood donors.
The American journal of clinical nutrition 68, 1075-1080 [PubMed:9808225]
[show Abstract]
Reference intervals for long-term status measures of folate, riboflavin, thiamine, and vitamin B-6 were determined in a select group of adults. Reference subjects had no adverse medical history and did not use tobacco, alcohol, or nutritional supplements, and their diets met > or =70% of the Australian recommended dietary intake for nutrients. Red blood cell concentrations of thiamine and folate were measured by microbiological methods. Vitamin B-6 and riboflavin status were measured on the basis of the erythrocyte aspartate transaminase activity coefficient and erythrocyte glutathione reductase activity coefficient, respectively. A survey of first-time blood donors, which was conducted in Australia in 1995, revealed a significant prevalence of low red blood cell thiamine concentrations (13%) when compared with the calculated normal reference intervals. However, the most important finding in the survey was that the group of healthy, nonanemic adults (first-time blood donors) was found to have a median red blood cell folate concentration 24% below the median concentration of the carefully selected (nonsupplemented) reference group. Plasma total homocysteine concentrations indicated folate deficiency in the reference group. Therefore, the 2.5th percentile cutoff for reference group red blood cell folate concentrations may have underestimated the prevalence of folate deficiency in the survey group. These data, coupled with the lack of Australian food-composition data for folate in particular, reinforce the need for monitoring nutritional status by both dietary and biochemical means. We recommend consideration of mandatory fortification of the Australian food supply with folic acid. | Switzer BR, Stark AH, Atwood JR, Ritenbaugh C, Travis RG, Wu HM (1997)
Development of a urinary riboflavin adherence marker for a wheat bran fiber community intervention trial.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 6, 439-442 [PubMed:9184778]
[show Abstract]
Development of a reliable marker of adherence to high-fiber diets is essential for accurately assessing dietary fiber intake in community interventions and clinical trials. The objective of this study was to evaluate the feasibility of using a riboflavin tracer incorporated into wheat bran cereal to determine fiber intake and compare results to the more traditional methodology of measuring stool weight. The inpatient phase of the study established that the excretion of urinary riboflavin was highly correlated with the dose of the riboflavin-spiked wheat bran cereal (r = 0.95, P < 0.005) and could be used as a biomarker to validate fiber supplement intake. The outpatient clinical intervention included a group of seven African-American men and women, who were asked to incorporate 1/2 cup of wheat bran cereal (11.6 g of dietary fiber) into their daily diet for a 6-week period. The cereal was spiked with a 28-mg dose of riboflavin. Baseline measurements of urinary riboflavin and stool weight were compared to postintervention levels. Comparison of pre- and postintervention measures of riboflavin excretion showed a significant increase (0.8 +/- 0.1 versus 6.0 +/- 0.6 mg/day, P < 0.02), which confirmed a high level of adherence to the dietary intervention. Although wet stool weights at baseline were significantly lower than postintervention (106 +/- 20 versus 146 +/- 23 g/day; P < 0.03), differences in dry stool weights did not reach significant levels (28 +/- 4 versus 33 +/- 5 g/day, P < 0.30). Furthermore, pre- and poststool measurements overlapped and could not provide definitive data on participant adherence. These results indicate that the riboflavin tracer was a more sensitive biomarker of wheat bran fiber supplementation than stool weight and provided an accurate method for validating adherence to the dietary intervention. A riboflavin marker provides a valid technique for adherence assessment in large-scale community trials, in which collection of 3-day fecal samples is not a manageable option. | Mulherin DM, Thurnham DI, Situnayake RD (1996)
Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis.
Annals of the rheumatic diseases 55, 837-840 [PubMed:8976642]
[show Abstract]
ObjectiveTo measure erythrocyte glutathione reductase (EGR) activity and riboflavin status, and their relations to disease activity, in rheumatoid arthritis patients compared to healthy controls.MethodsPatients with rheumatoid arthritis were classified as active if there were features of articular inflammation which required initiation or change of disease modifying therapy, and as inactive if they had little evidence of articular inflammation. EGR was measured in patients and healthy controls by a functional assay with or without the addition of flavin adenine dinucleotide (FAD). The ratio of stimulated EGR (with FAD added) to basal EGR (no added FAD), which measures riboflavin status, is known as the EGR activation coefficient (EGRAC). An EGRAC > or = 1.3 represents biochemical riboflavin deficiency.Results91 patients with rheumatoid arthritis, including 57 with active disease, and 220 healthy controls were studied. Both basal and stimulated EGR were significantly higher in patients with rheumatoid arthritis (P = 0.0001) than in controls. Biochemical riboflavin deficiency was identified in 41% controls and 33% patients with active rheumatoid arthritis but was significantly less frequent (9%) in patients with inactive compared to active disease (P = 0.02) or healthy controls (P = 0.0006). Pain score, articular index, C reactive protein, and erythrocyte sedimentation rate were increased in patients with riboflavin deficiency (all P < 0.02).ConclusionsHigher basal and stimulated EGR might be expected in patients with rheumatoid arthritis in response to chronic oxidative stress due to synovial inflammation. The association of riboflavin deficiency with increased disease activity suggests that impaired EGR activity could facilitate continuing inflammation in these patients. | Zempleni J, Galloway JR, McCormick DB (1996)
Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans.
The American journal of clinical nutrition 63, 54-66 [PubMed:8604671]
[show Abstract]
The pharmacokinetics and utilization (flavocoenzyme synthesis) of orally and intravenously administered riboflavin in healthy humans were assessed. After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females (control period), each of these subjects received three different oral riboflavin doses (20, 40, and 60 mg) and one intravenous bolus injection of riboflavin (11.6 mg). Vitamins were administered in a randomized, cross-over design with 2 wk between each administration. Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration. Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma; riboflavin was assayed in urine. During the control period, a small circadian variation was observed: plasma concentrations and urinary excretion of riboflavin were low during the afternoon (P < 0.05). Pharmacokinetics were calculated using a two-compartment open model. The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult. Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration (P < 0.01). Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations. 7 alpha-Hydroxyriboflavin was identified in plasma. Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma. No sex differences were observed for any of the pharmacokinetic variables (P > 0.05). | Kodentsova VM, Vrzhesinskaya OA, Spirichev VB (1995)
Fluorometric riboflavin titration in plasma by riboflavin-binding apoprotein as a method for vitamin B2 status assessment.
Annals of nutrition & metabolism 39, 355-360 [PubMed:8678471]
[show Abstract]
A method for plasma riboflavin determination by riboflavin-binding apoprotein titration has been proposed for vitamin B2 status evaluation. The method is based on the formation of riboflavin-apoprotein complex accompanied by full loss of fluorescence peculiar to free riboflavin. The data obtained have demonstrated a correlation with indicators of the vitamin B2 status such as urinary excretion, erythrocyte content, and stimulation of the glutathione reductase activity by flavin adenine dinucleotide. Levels > 6 ng/ml blood plasma may be considered to be a criterion for normal vitamin B2 supply. | Dror Y, Stern F, Komarnitsky M (1994)
Optimal and stable conditions for the determination of erythrocyte glutathione reductase activation coefficient to evaluate riboflavin status.
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 64, 257-262 [PubMed:7883462]
[show Abstract]
To measure the activation coefficient (AC) of erythrocyte glutathione reductase (GR), suspended whole blood was lysed in a preincubation solution, with or without 100 microM flavin adenine dinucleotide (FAD). Upon addition of the reaction mixture, FAD concentration decreased about 10-fold. No AC values < 1 were obtained in any of the subjects. The range of unstimulated activity per g hemoglobin (Hb) was 5 to 12 U. AC values of healthy subjects (1.3) decreased to about 1.15 after vitamin supplementation of 1 RDA for 3 wk. In healthy young subjects consumption of dietary riboflavin at levels as low as 0.5 mg/d resulted in an AC of 1.6. | Boisvert WA, Mendoza I, Castañeda C, De Portocarrero L, Solomons NW, Gershoff SN, Russell RM (1993)
Riboflavin requirement of healthy elderly humans and its relationship to macronutrient composition of the diet.
The Journal of nutrition 123, 915-925 [PubMed:8487103]
[show Abstract]
The riboflavin requirements of two groups of riboflavin-deficient, but otherwise healthy, Guatemalan elderly persons over the age of 60 y were studied by varying the fat:carbohydrate ratio in two diets. The first group consumed a diet similar in macronutrient content to a Western-type diet with low carbohydrate and high fat; the second group consumed a typical Guatemalan diet with high carbohydrate and low fat. Energy and protein intakes of both groups were similar. Riboflavin status was monitored by weekly measurements of erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Increasing increments of riboflavin were added to the subjects' diets until their status was normalized, as indicated by EGRAC of < 1.34 and a sharp increase in urinary riboflavin excretion. Using the EGRAC method, the mean value of riboflavin intake at which the subjects' EGRAC reached the limit of normality was 1.37 +/- 0.03 mg/d in the first phase and 1.29 +/- 0.03 mg/d in the second phase. The sharp increase in urinary excretion occurred at riboflavin intakes of 1.13 and 1.03 mg/d for Groups 1 and 2, respectively. Thus, the differences between the two groups suggest that diets with a lower fat:carbohydrate ratio can decrease the dietary need for riboflavin. The dietary requirement of riboflavin, as estimated by the more reliable urinary excretion method, was 1.1-1.3 mg/d for those consuming the Western-type diet, which is similar to values found over 40 y ago in young adults. We conclude that the dietary requirements of riboflavin in the elderly do not differ from those of young adults. | Brun TA, Chen J, Campbell TC, Boreham J, Feng Z, Parpia B, Shen TF, Li M (1990)
Urinary riboflavin excretion after a load test in rural China as a measure of possible riboflavin deficiency.
European journal of clinical nutrition 44, 195-206 [PubMed:2369885]
[show Abstract]
Urinary excretion of riboflavin was measured in 3318 adults 4 h after an oral dose of riboflavin. Male and female subjects aged 35-64 years were selected from 65 mostly rural counties located in 24 provinces of China. Counties were selected to represent a range of seven of the most prevalent cancer mortality rates in China and within counties households were selected at random. Urinary riboflavin excretion levels after a load test, erythrocyte glutathione reductase activity coefficients (EGR-AC), dietary riboflavin intakes, and a large number of other biochemical, dietary, and environmental parameters were measured. Mean dietary intake of riboflavin was 75 per cent of the Chinese recommended dietary allowances (CRDA). Mean meat intake per reference man was very low (26.4 +/- 23.7 g/d) in comparison to Western standards and milk was not consumed at all in most counties. Mean EGR activity coefficients measured on 'blood pools' for both males (1.47 +/- 0.14) and females (1.48 +/- 0.16) indicated that more than two-thirds of the population surveyed was in the medium or high risk category of riboflavin deficiency. Using current reference standards of less than 1.4 mg for 4-h urinary excretion of riboflavin after a 5 mg load, more than 70 per cent of the individuals examined exhibited low levels usually associated with high risk of riboflavin deficiency. In view of the lack of specificity for clinical indications of riboflavin deficiency and the tentative validity of the present CRDA, the interpretation of the data is problematic. We suggest that the present CRDA for this vitamin is set too high and requires critical review and possibly some revision. | Ajayi OA (1989)
Bioavailability of riboflavin from fortified palm juice.
Plant foods for human nutrition (Dordrecht, Netherlands) 39, 375-380 [PubMed:2631092]
[show Abstract]
The bioavailability of riboflavin from fortified palm juice was assessed in young adult men, Riboflavin status was assessed from urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient (EGR-AC) while iron status was assessed from haemoglobin and serum ferritin concentrations. Although the consumption of unfortified palm juice made significant contribution to the meager riboflavin intake, it conferred no metabolic advantage. The consumption of fortified palm juice produced a marked reduction in EGR-AC values and a significant increase in urinary riboflavin excretion. Since iron release from storage sites may be flavin dependent, riboflavin deficiency may affect iron utilization. Fortification may prove effective in alleviating nutrient deficiencies, but the carrier vehicle must be acceptable to all age groups. | Baeckert PA, Greene HL, Fritz I, Oelberg DG, Adcock EW (1988)
Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin.
The Journal of pediatrics 113, 1057-1065 [PubMed:3142982]
[show Abstract]
Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful. | Bamji MS, Bhaskaram P, Jacob CM (1987)
Urinary riboflavin excretion and erythrocyte glutathione reductase activity in preschool children suffering from upper respiratory infections and measles.
Annals of nutrition & metabolism 31, 191-196 [PubMed:3592624]
[show Abstract]
The urinary and blood levels of riboflavin and erythrocyte glutathione reductase (EGR) activity and its stimulation with FAD (EGR-AC) were examined in preschool children suffering from either measles or other upper respiratory infections and matched controls. Patients showed significantly higher levels of urinary riboflavin (per unit creatinine), erythrocyte riboflavin and EGR activity and lower EGR-AC values. This trend reversed after treatment. Mobilization of riboflavin from a labile tissue pool during infections may produce artefactual changes in the biochemical indices of riboflavin status. It would also prevent tissue saturation despite supplementation. | Bates CJ, Powers HJ (1985)
A simple fluorimetric assay for pyridoxamine phosphate oxidase in erythrocyte haemolysates: effects of riboflavin supplementation and of glucose 6-phosphate dehydrogenase deficiency.
Human nutrition. Clinical nutrition 39, 107-115 [PubMed:4019261]
[show Abstract]
The formation of pyridoxal and its phosphate from pyridoxamine phosphate by red cell haemolysates was measured in a centrifugal analyser by the formation of the fluorescent adduct with semicarbazide. Pyridoxal phosphate was found to react more rapidly than pyridoxal, thus permitting a distinction between the two products, and hence the measurement of phosphatase activity. Activity of the enzyme, pyridoxamine phosphate:oxygen oxidoreductase (deaminating) EC 1.4.3.5 (PPO) was measured in haemolysates from 72 Gambian women with evidence of riboflavin deficiency, and was repeated after 6 weeks of placebo or riboflavin supplementation. Those who received the riboflavin supplement responded with a marked increase in PPO activity, which was matched by a decrease in the activation coefficient (AC) of erythrocyte NAD(P)H2:glutathione oxidoreductase, EC 1.6.4.2 (glutathione reductase, EGR). No difference between the supplemented and unsupplemented groups was observed in the capacity of haemolysates to hydrolyse pyridoxal 5-phosphate, nor in the extent of activation of erythrocyte L-aspartate:2-oxoglutarate aminotransferase EC 2.6.1.1. by pyridoxal phosphate. Although the three subjects with low levels of D-glucose 6-phosphate: NADP 1-oxidoreductase EC 1.1.1.49 (G6P-D) had, as expected, correspondingly low AC's of EGR, their unsupplemented activities of PPO were in the same low range as those of the G6P-D-normal subjects, and they responded as G6P-D-normal subjects did to riboflavin supplementation. PPO thus does not appear to resemble EGR in retaining its flavin coenzyme during riboflavin depletion.(ABSTRACT TRUNCATED AT 250 WORDS) | Thurnham DI, Zheng SF, Munoz N, Crespi M, Grassi A, Hambidge KM, Chai TF (1985)
Comparison of riboflavin, vitamin A, and zinc status of Chinese populations at high and low risk for esophageal cancer.
Nutrition and cancer 7, 131-143 [PubMed:3878498]
[show Abstract]
In two surveys in The Peoples Republic of China, blood samples were collected for nutritional studies in two counties where the risks of esophageal cancer are very different. The first survey was done in May 1980 in Linxian County (Henan Province) where the risk of esophageal cancer is very high. Blood samples were obtained from 111 persons (58 men, 53 women) who were selected randomly from 528 subjects that underwent endoscopical examination. The second survey was done in May 1981 in Jiaoxian County (Shandong Province) where the risk of esophageal cancer is reported to be relatively low. Blood samples were obtained from 120 persons (66 men, 54 women) who were selected randomly from 252 subjects that had also had undergone endoscopy. The blood samples were used to measure the nutritional status of riboflavin (erythrocyte glutathione reductase activation coefficient), vitamin A (retinol and carotene concentrations), and zinc (plasma and hair zinc concentrations). Only riboflavin status was significantly different in the two communities. The distribution of erythrocyte glutathione reductase activation coefficient values suggested that riboflavin status was much better in the low-risk community. Also in May 1981, a few more blood samples were obtained from some of the participants of the previous year's study in Linxian. A slight improvement in riboflavin and zinc status was detected. We considered the possibility that these changes may have been linked to the socioeconomic changes currently taking place in rural areas. Data were also collected from food allocation records in 15 production brigades in Linxian and 13 production brigades in Jiaoxian in the same years. The records used represented the food consumption of 3,491 and 2,552 persons, respectively, and were used to calculate daily food and nutrient intakes in the two communities. Dietary analyses highlighted the vegetarian nature of the diet, the low consumption of riboflavin, and the virtual dependence on carotene for vitamin A. Both communities consumed very little in the way of animal products or fruit, but intake of these items was higher in Jiaoxian. | Belko AZ, Obarzanek E, Roach R, Rotter M, Urban G, Weinberg S, Roe DA (1984)
Effects of aerobic exercise and weight loss on riboflavin requirements of moderately obese, marginally deficient young women.
The American journal of clinical nutrition 40, 553-561 [PubMed:6475825]
[show Abstract]
In a previous study, exercise was shown to increase riboflavin requirements of active, normal weight young women. The present study examined the effect of exercise and weight loss on riboflavin status of moderately overweight women. The experiment was designed as a two-period cross-over with an initial base-line period and two 5-wk metabolic periods. The basic diet contained 1200 kcal with a riboflavin concentration of 0.8 mg/1000 kcal. Exercise consisted of a program of dance exercise. Riboflavin depletion, as measured by increased erythrocyte glutathione reductase activity coefficients and decreased urinary excretion of riboflavin, occurred during both nonexercise and exercise periods. Erythrocyte glutathione reductase activity coefficients increased from a base-line mean of 1.28 +/- 0.11 to 1.40 +/- 0.12 during nonexercise and to 1.49 +/- 0.16 during exercise. Urinary excretion of riboflavin fell from 48 +/- 12% of intake during base-line to 30 +/- 13% during nonexercise and to 19 +/- 6% during exercise. Riboflavin depletion was not related to the rate or composition of weight loss or to change in aerobic capacity. | Alexander M, Emanuel G, Golin T, Pinto JT, Rivlin RS (1984)
Relation of riboflavin nutriture in healthy elderly to intake of calcium and vitamin supplements: evidence against riboflavin supplementation.
The American journal of clinical nutrition 39, 540-546 [PubMed:6546833]
[show Abstract]
The status of riboflavin nutriture was evaluated in 24 healthy elderly female residents of a private, nonprofit facility for the care of ambulatory elderly. Riboflavin intake by history was greater than or equal to the recommended dietary allowances (RDA) for this nutrient in all but three subjects, and the average intake in the group as a whole was 50% greater than the RDA. Confirmatory of the findings by history, the status of riboflavin nutriture was excellent in nearly all subjects as evaluated by urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient. By contrast, calcium intake was greater than or equal to the RDA in ony four of the 24 subjects. The adequacy of calcium intake was found to depend upon a sufficiently high percentage of the total dietary intake of riboflavin being derived from milk and dairy products. It was observed that individual calcium intakes were less than 80% of the RDA unless 40% or more of the total intake of riboflavin was derived from milk and dairy products rather than from other food sources. In those subjects taking daily supplementation with a single multivitamin tablet containing low levels of riboflavin, the total intake of riboflavin and its urinary excretion were increased similarly, suggesting that even small amounts of riboflavin are not retained by elderly subjects consuming a diet adequate in riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS) | Maiani G, Mobarhan S, Nicastro A, Virgili F, Scaccini C, Ferro-Luzzi A (1983)
[Determination of glutathione reductase activity in erythrocytes and whole blood as an indicator of riboflavin nutrition].
Acta vitaminologica et enzymologica 5, 171-178 [PubMed:6650303]
[show Abstract]
Recent developments in riboflavin statis assessment suggest the possibility of satisfactory replacement of the method based on the determination of glutathione reductase (GRe) (EC 1, 6, 4, 2) activity in erythrocytes by one on whole blood. The advantages would be the elimination of the steps of separation and washing of the erythrocytes, which may be of problematic execution under the difficult logistic conditions of field studies. In order to verify the interchangeability of the two methods, we have undertaken a comparison of the results obtained on 81 subjects. Our data show that the results of the whole blood method closely replicate those obtained on the erythrocytes and that all cases are correctly classified in terms of riboflavin status assessment. A linear regression analysis shows that the two methods overlap perfectly, with a highly significant (P less than 1%) correlation coefficient (r = 0.82). Sixty five percent of the variance of the dependent variable (CA GRsi) is accounted for by the variation of the independent variable CA GRe). | Bates CJ, Prentice AM, Paul AA, Prentice A, Sutcliffe BA, Whitehead RG (1982)
Riboflavin status in infants born in rural Gambia, and the effect of a weaning food supplement.
Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 253-258 [PubMed:7101408]
[show Abstract]
Riboflavin status was measured in infants between birth and two years of age, by the erythrocyte glutathione reductase (NAD(P)H2: glutathione oxidoreductase, EC 1.6.4.2) test on finger-prick blood samples. The infants were living in three rural Gambian villages: Keneba, Manduar and Kanton Kundar; those in Keneba were receiving a weaning food supplement between three and 12 months, which provided 0.15 to 0.20 mg riboflavin per day, in addition to their normal intake from breast milk and locally available weaning foods, which provided 0.13 to 0.21 mg/day over the same age range. On the basis of currently accepted criteria of biochemical normality, the unsupplemented infants were born deficient and, in the absence of a supplement, remained so throughout their first two years of life, with only a minor, short-lived improvement during the first few months. In the supplemented group, however, riboflavin status fell within normal limits for the duration of the supplement, but rapidly deteriorated again once the supplement was withdrawn. It is concluded that infants born to deficient mothers are usually deficient at birth, and remain so throughout suckling and weaning on to locally available foods. The daily requirement, to achieve satisfactory biochemical status, is thus greater than 0.13 to 0.21 mg/day, and probably approaches 0.4 mg/day, for most individuals up to the age of one year. | Dastur DK, Santhadevi N, Quadros EV, Avari FC, Wadia NH, Desai MN, Bharucha EP (1976)
The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships.
The British journal of nutrition 36, 143-159 [PubMed:182198]
[show Abstract]
1. The B-vitamin status of fifty-nine patients, mainly from the lower socio-economic classes in Bombay, with a history of chronic malnutrition, and of alcoholism of 1-5-20 years' duration, was studied before and during treatment, and in relation to their clinical, especially neurological, condition. These patients were divided into two neurological categories: (I) those with peripheral neuropathy (mainly sensory and distal) alone, (2) those with mental changes (mainly confusion and disorientation) also. Both categories frequently showed pellagrous pigmentation and mucocutaneous signs of B-vitamin deficiency. 2. Thiamin and erythrocyte transketolase (EC 2.2.1.1) activity, riboflavin, nicotinic acid, pantothenic acid, total and pyridoxal fraction of vitamin B6, folate and total vitamin B12 were estimated in the blood and the cerebrospinal fluid (CSF) of these patients, and also in the blood of sixty-nine control subjects and in the CSF of some of them. The concentrations of all the vitamins, except vitamin B12, were highly significantly lower in the blood of patients of category I compared to the controls, and erythrocyte transketolase activity and pyridoxal concentration in patients of category 2 were significantly lower than those of category I patients. Blood pantothenic acid and folate concentrations were reduced less consistently. 3. Serum vitamin B12 concentration was significantly increased (though within normal range) in the patients compared to the control group, probably because of the moderate hepatic insufficiency (as assessed by liver function tests) in the former. 4. The concentrations of thiamin, riboflavin, nicotinic acid and total vitamin B6 were also highly significantly lower in the CSF in patients of category I compared with controls. Furthermore, thiamin, nicotinic acid and total vitamin B6 concentrations were significantly lower in patients of category 2 than those of category I patients, indicating that CSF levels reflect better the neurological status of these patients. 5. There was a moderate increase in the blood concentration of all the vitamins tested, after a relatively poor hospital diet alone. There was a concurrent increase in the blood levels of thiamin, riboflavin, nicotinic acid and pantothenic acid after parenteral treatment with either thiamin or nicotinic acid. The administration of pyridoxine resulted in a significant increase in the blood levels of riboflavin and the pyridoxal fraction of vitamin B6. | Treadwell GE, Metzler DE (1972)
Photoconversion of riboflavin to lumichrome in plant tissues.
Plant physiology 49, 991-993 [PubMed:16658098]
[show Abstract]
Free flavins have been extracted from shoots of etiolated corn (Zea mays L., var. Burpee Snowcross) and from yeast cells and separated from other substances by absorption on resorcinol-formaldehyde resin and talc columns and by thin layer chromatography. Riboflavin was the only free flavin present. Extracts of etiolated shoots of oats (Avena sativa L., var. Multiline E-69 and Clinford) yielded riboflavin plus a second free flavin previously demonstrated in oats. The areas of the chromatograms expected to contain lumichrome were completely clear. After illumination of any of the three organisms with artificial light (1100 ft-c) or sunlight for 6 hours, lumichrome (7,8-dimethylalloxazine) was found. In corn shoots after irradiation by sunlight, the amount of lumichrome present was equivalent to 2.5% of the total free flavin. Lumichrome was identified by thin layer chromatography in six solvent systems (including two two-dimensional systems), by its characteristic fluorescence in acetic acid, by its absorption spectrum, and by formation of a characteristic hydrate in ammonia-containing solutions. A comparison was made with in vitro photolysis of riboflavin and the possible role of photolysis of riboflavin (either free or bound) and of lumichrome formation in photo-responses of plants is discussed. Placing the shoots in the dark for 4 hours after irradiation in sunlight for 6 hours led to no detectable loss of the lumichrome which had been formed. |
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