Grundinformationen
- Standard-SMILES
Cc1cc2nc3c(=O)[nH]c(=O)nc-3n(C[C@H](O)[C@H](O)[C@H](O)CO)c2cc1C- InChIKey
AUNGANRZJHBGPY-SCRDCRAPSA-N- Summenformel
- C17H20N4O6
- Durchschnittliche Molmasse
- 376,4 g/mol
- Monoisotopische Masse
- 376,13828436
Überblick
Riboflavin is 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. It has a role as an antioxidant, a cofactor, a photosensitizing agent, an anti-inflammatory agent, a mouse metabolite, a plant metabolite, an Escherichia coli metabolite, a food colouring, a fundamental metabolite and a human urinary metabolite. It is a vitamin B2 and a flavin. It is a conjugate acid of a riboflavin(1-).
Namen und Bezeichner
- Bevorzugter Name
- Riboflavin
- IUPAC
- 7,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4-dione
- Lokaler Name
- Riboflavin
- Englischer Name
- Riboflavin
- Summenformel
- C17H20N4O6
- Molmasse
- 376.36
Namen und Synonyme
Weitere Namen anzeigen
Datenbank-Bezeichner
- CAS
83-88-5- PubChem CID
- 493570
- DTXSID
DTXSID8021777- ChEMBL
CHEMBL1534- ChEBI
CHEBI:17015- UNII
- TLM2976OFR
- EC Number
- 201-507-1
- Nikkaji
- J3.876H
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- -1,5
- Polarare Oberfläche (TPSA)
- 155 Ų
- H-Brücken-Donoren
- 5
- H-Brücken-Akzeptoren
- 7
- Frei drehbare Bindungen
- 5
- Schwere Atome
- 27
- Formalladung
- 0
- Komplexität
- 680
Experimentelle und physikochemische Eigenschaften
LogP
log Kow = -1.46
-1.46
-1.46
-0.55
Food Additives
Foods -> FDA Regulatory Status of Color Additives
COLOR OR COLORING ADJUNCT, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT -> FDA Substance added to food
Color/Form
Fine orange-yellow needles from 2N acetic acid, alcohol, water, or pyridine ... three different crystal forms
Orange to yellow crystals or needles
Solubility
Soluble in sodium chloride solutions; 0.0045 g/100 mL of absolute ethanol at 27.5 °C; slightly sol in cyclohexanol, amyl acetate and benzyl alcohol, phenol; insoluble in ether, chloroform, acetone, benzene; very soluble in dilute alkalies (with decomposition)
SOLUBILITY IN WATER AT 25 °C: 10-13 MG/100 ML
Slightly soluble in alcohols; insoluble in lipid solvents
Insoluble in ethyl ether, acetone, chloroform; slightly soluble in ethanol
In water, of 0.1 g/L at 20 °C; 0.071 g/L and 0.085 g/L at 25 °C
Physikochemische Eigenschaften
- Schmelzpunkt
- 290 °C · 290 °C (dec.)(lit.)
- Siedepunkt
- 504.93 °C · 504.93°C (rough estimate)
- Dichte
- 1.2112 · 1.2112 (rough estimate)
- Brechungsindex
- -135 ° · -135 ° (C=0.5, JP Method)
- Flammpunkt
- 9 ℃ · 9℃
- storage temp.
- 2 · 2-8°C
- Löslichkeit
- Very slightly soluble in water, practically insoluble in ethanol (96 per cent). Solutions deteriorate on exposure to light, especially in the presence of alkali. It shows polymorphism (5.9).
- Aggregatzustand
- Powder
- pka
- 1.7 · 1.7(at 25℃)
- Farbe
- Yellow to orange
- PH
- 5.5 · 5.5-7.2 (0.07g/l, H2O, 20°C)
- Geruch (Odor)
- Slight odour
- Biologische Quelle
- synthetic
- Wasserlöslichkeit
- 0.07 g/L · 0.07 g/L (20 ºC)
- Merck
- 14 · 14,8200
- BRN
- 97825 · 97825
- BCS Class
- 1 · 1
- Stabilität
- Stable, but light-sensitive. Incompatible with strong oxidizing agents, reducing agents, bases, calcium, metallic salts. May be moisture sensitive.
- Kosmetik-Inhaltsstoffe Funktionen
- SKIN CONDITIONING - MISCELLANEOUSCOLORANT
- 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
- InChIKey
- AUNGANRZJHBGPY-SCRDCRAPSA-N
- SMILES
- CC1=C(C)C=C(N(C[C@H](O)[C@@H]([C@H](O)CO)O)C(C2=N3)=NC(NC2=O)=O)C3=C1
- LogP
- -2.009 · -2.009 (est)
- CAS Datenbank
- 83 · 83-88-5(CAS DataBase Reference)
- NIST chemische Informationen
- Riboflavine(83-88-5)
- EPA chemische Informationen
- Riboflavin (83-88-5)
Sicherheit und Regulatorisches
GHS-Klassifizierung
GHS Classification
This chemical does not meet GHS hazard criteria for 98.4% (122 of 124) of all reports.
Not Classified
Aggregated GHS information provided per 124 reports by companies from 4 notifications to the ECHA C&L Inventory.
Gefahrenhinweise
Regulatory Information
Chemical: Riboflavin
Status: Active Update: 25-10-2017 https://echa.europa.eu/registration-dossier/-/registered-dossier/20915
Riboflavin: Does not have an individual approval but may be used under an appropriate group standard
FDA Requirements
Certification of this color additive when used as a food is not necessary for the protection of the public health and therefore batches thereof are exempt from the requirements of section 706(c) of the Federal Food, Drug, and Cosmetic Act.
Substance added directly to human food affirmed as generally recognized as safe (GRAS).
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: riboflavin is included in weight control drug products.
Riboflavin used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
Special Reports
NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press, Washington, D.C. (1998).[Available from, as of March 2, 2010: http://www.nap.edu/catalog/6015.html]
Sicherheit und Schutzausrüstung
First Aid Measures
Fresh air, rest.
Rinse and then wash skin with water and soap.
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
Disposal Methods
SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.
SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Toxikologische Informationen
Interactions
Riboflavin interrelates with other B vitamins, notably niacin, which requires riboflavin for its formation from tryptophan, and vitamin B6, which also requires riboflavin for a conversion to a conenzyme form. These interrelationships are not known to affect the requirement for riboflavin.
The rate and extent of absorption of riboflavin are reportedly affected by propantheline bromide. Prior administration of propantheline bromide delayed the rate of absorption of riboflavin but increased the total amount absorbed, presumably by increasing the residence time of riboflavin at GI absorption sites.
Alcohol impairs intestinal absorption of riboflavin.
Concurrent use /with probenecid/ decreases gastrointestinal absorption of riboflavin; requirements for riboflavin may be increased in patients receiving probenecid.
For more Interactions (Complete) data for Riboflavin (7 total), please visit the HSDB record page.
Adverse Effects
Riboflavin is relatively safe to administer as it has limited water solubility, and enterocytes do not absorb the excess. However, caution is necessary when administering large doses to pregnant women. Riboflavin may cause benign urine discoloration.
Exposure Routes
The substance can be absorbed into the body by ingestion.
Vitamin B2 is readily absorbed from the upper gastrointestinal tract.
Milk Concentrations
No difference in riboflavin content of human milk was found between supplemented and unsupplemented well-nourished mothers at 6 months postpartum. Previously, estimates of the riboflavin content of human milk from well-nourished, unsupplemented mothers included 0.37 +/- 0.13 (standard deviation) mg/L at 5 to 7 days postpartum, 0.49 +/- 0.12 mg/L at 43 to 45 days postpartum, 0.24 +/- 0.35 mg/L at 6 months postpartum, and 0.35 +/- 0.02 mg/L after 3 weeks postpartum. More recent studies in five subjects showed that riboflavin in milk may have been previously underestimated as a result of a lack of detection of flavin-adenine dinucleotide (FAD), ... On the basis of this and studies of microbiologically determined riboflavin in human milk, a riboflavin concentration of 0.35 mg/L will be used for human milk consumed by infants younger than 6 months.
Toxicity Summary
No observable toxicities with intakes of riboflavin are from food sources many times the recommended daily allowance. Riboflavin has high water solubility and limited absorption. No adverse effects are from high riboflavin intakes from foods or supplements up to 400 mg daily for at least 3 months. The Food and Nutrition Board has not established the upper limit for riboflavin as it has a good safety profile. High-dose riboflavin does not cause toxicity as excess riboflavin is excreted in the urine.
Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase.
Signs and Symptoms
Cough. Sore throat.
Redness. Pain.
Natural Pollution Sources
Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, leafy vegetables. Richest natural source is yeast. Minute amounts present in all plant and animal cells. Occurs in free form only in retina of the eye, in whey, and in urine; Bioactive forms occurring in tissues and cells are riboflavin monophosphate and flavine-adenine dinucleotide.
Human Toxicity Excerpts
/SIGNS AND SYMPTOMS/ No adverse effects associated with riboflavin consumption from food or supplements have been reported. ... The apparent lack of harm resulting from high oral doses of riboflavin may be due to its limited solubility and limited capacity for absorption in the human gastrointestinal tract; /and/ its rapid excretion in the urine.
/CASE REPORTS/ A previously healthy 15-year-old boy... /developed anaphylaxis/ ... several times after he drank one soft drink or took a single multivitamin tablet .... In an outpatient clinic with the availability of complete resuscitative procedures, ... single-blind prick skin tests and intradermal skin tests /were performed/ on the patient with various pure vitamin components of the soft drink and the multivitamin tablet. Physiologic saline and histamine were used for negative and positive controls, respectively. RESULTS: Riboflavin, a component of both the soft drink and the vitamin tablet, produced positive reactions on intradermal skin tests in the patient. Positive reactions were not present in the normal control subjects. CONCLUSIONS: ... Free-form riboflavin may potentially be associated with an anaphylactic reaction...
/EPIDEMIOLOGY STUDIES/ ... Associations among intake of folate, vitamin B2, vitamin B6, vitamin B12, and polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes and breast cancer risk /were investigated/ in a Japanese population. A hospital based, case-control study was conducted in Nagano Prefecture, Japan, in 388 pairs of patients with histologically confirmed invasive breast cancer and age- and area-matched controls selected from medical checkup examinees. Energy-adjusted intakes of folate and other B vitamins were derived from a validated food frequency questionnaire. Genotyping was completed for MTHFR (C677T and A1298T) and MTR (A2756G). Odds ratios and 95% confidence intervals were calculated by the conditional logistical regression model. Median dietary folate intake (ug/day) in the control group was 438.2 (interquartile range: 354.9-542.9). Neither dietary intake of folate, vitamin B2, vitamin B6, or vitamin B12 nor polymorphisms of MTHFR or MTR genes were significantly associated with breast cancer risk. Further, no significant interaction was found among nutrients, polymorphisms, and breast cancer risk. Associations of nutrients with breast cancer risk did not differ by hormone receptors status. ... Dietary intake of folate and related B vitamins and genotypes of MTHFR or MTR /had/ no overall association with breast cancer risk in Japanese women.
/EPIDEMIOLOGY STUDIES/ ... A case-control study /was conducted/ to investigate the association of nutrient intake involved in the one-carbon pathway of folate for DNA methylation and DNA synthesis and the related enzyme genetic polymorphisms with colorectal cancer. Cases were 107 patients newly diagnosed with colorectal cancer. Controls were 224 subjects matched with cases by sex, age, and residential area. Nutrient intake was assessed by a self-administered, semiquantitative food-frequency questionnaire. Four genetic polymorphisms-MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys-were determined using blood samples. Odds ratios were calculated using conditional logistic regression analysis adjusted for smoking, alcohol consumption, body mass index, and dietary fiber intake. Although folate intake was inversely associated with colorectal cancer, this association was attenuated after further controlling for dietary fiber intake. Neither vitamin B6, vitamin B12, nor vitamin B2, nor any genetic polymorphism was significantly associated with colorectal cancer...
For more Human Toxicity Excerpts (Complete) data for Riboflavin (7 total), please visit the HSDB record page.
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
riboflavin
DILI Negative
Oral
DOI:10.1016/j.drudis.2019.09.022
Non-Human Toxicity Excerpts
/LABORATORY ANIMALS: Acute Exposure/ Vitamin B2 is practically non-toxic; 10 g/kg administered orally to rats resulted in no toxic effects.
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... The effects of excess thiamin or riboflavin administration on body weight gain, food intake, tissue weights, and urinary excretion of B-group vitamins /were investigated/ in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0006% thiamin-HCl or the same diet with 0.006%, 0.03%, 0.18% or 1.0% thiamin-HCl for 30 days, or the diet containing 0.0006% riboflavin or the same diet with 0.1%, 0.5 or 1.0% riboflavin for 22 days. Mild diarrhea was seen only in the rats fed with 1.0% thiamin-HCl diet. Excess thiamin-HCl or riboflavin did not affect body weight gains, food intake or tissue weights. The urinary excretions of water-soluble vitamins also did not differ among the diets. These results clearly showed that feeding a diet containing up to 1.0% thiamin-HCl or 1.0% riboflavin did not induce apparent adverse effects, and the no-observed-adverse-effect-levels (NOAELs) for thiamin-HCl and riboflavin in rats might be 1.0% in diet...
/IMMUNOTOXICITY/ Inhibitory effects of highly purified vitamin B2 (riboflavin-5'-sodium phosphate, >97%) on the interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 and nitric oxide (NO) in LPS-induced shock mice were evaluated. Vitamin B2 at 20 mg/kg (protective effect on mice mortality induced by LPS), intravenously administered 6 hr after LPS injection, significantly decreased the plasma elevated levels of IL-6 and MIP-2 at 9 and 12 hr. In addition, vitamin B2 lowered the tissue concentration and the mRNA expression of IL-6 in lung and those of MIP-2 in liver at 9 hr. Vitamin B2 also reduced concentration of MIP-2 concentration in lung, and inhibited mRNA expression in kidney, respectively. Vitamin B2 decreased the plasma elevated NO levels in accordance with a reduction in expression of inducible NO synthase (iNOS) both at 21 and 24 hr. Accordingly, the reduction in elevated plasma cytokine levels and NO based on the inhibitory effect on local cytokine mRNA expression and iNOS would be responsible for the anti-septic effect of vitamin B2.
/OTHER TOXICITY INFORMATION/ There are no data from animal studies suggesting that uptake of riboflavin during pregnancy presents a potential hazard for the fetus or newborn.
For more Non-Human Toxicity Excerpts (Complete) data for Riboflavin (6 total), please visit the HSDB record page.
Regulatorische Informationen
FDA Requirements
Certification of this color additive when used as a food is not necessary for the protection of the public health and therefore batches thereof are exempt from the requirements of section 706(c) of the Federal Food, Drug, and Cosmetic Act.
Substance added directly to human food affirmed as generally recognized as safe (GRAS).
Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: riboflavin is included in weight control drug products.
Riboflavin used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.
Sicherheitsdaten
- F
- 8-10-21
- wgk
- 1
- tsca
- TSCA listed
- ridadr
- UN1230 - class 3 - PG 2 - Methanol, solution
- hs_code
- 29362300
- RTECS-Nr.
- VJ1400000
- risk_code
- 11-23/24/25-39/23/24/25
- Toxizität
- LD50 in rats (g/kg): >10 orally, 5.0 s.c., 0.56 i.p. (Unna, Greslin)
- hazard_code
- F,T
- safety_code
- 24/25-45-36/37-16
- Speicherklasse
- 11 - Combustible Solids
- Giftige Stoffe Daten
- 83-88-5(Hazardous Substances Data)
Chemie und Industrie
Pharmakologische Informationen
ATC Code
S - Sensory organs
A - Alimentary tract and metabolism
QS - Sensory organs
QA - Alimentary tract and metabolism
A11HA04
Bionecessity
Riboflavin (vitamin B2) functions as a coenzyme for numerous oxidation-reduction reactions in several metabolic pathways and in energy production. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. The requirements for riboflavin are based on intake in relation to a combination of indicators, including the excretion of riboflavin and its metabolites, blood values for riboflavin, and the erythrocyte glutathione reductase activity coefficient ... DRI values are listed by life stage group in the table.
State of deficiency: ariboflavinosis is characterized by cheilosis, angular stomatitis, glossitis, seborrheic dermatitis of nose and scrotum, and corneal vascularization ... Riboflavin deficiency seldom occurs alone; it often is observed with pellagra and other B-complex deficiency states ...
State of deficiency: ocular symptoms /of ariboflavinosis/ include pruritis, burning, blepharospasm, photophobia, and visual impairment.
Women pregnant with more than one fetus and those breastfeeding more than one infant are also likely to require more riboflavin.
For more Bionecessity (Complete) data for Riboflavin (43 total), please visit the HSDB record page.
Pharmacodynamics
Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts.
Mechanism of Action
Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase.
Riboflavin is converted to 2 coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are necessary for normal tissue respiration. Riboflavin is also required for activation of pyridoxine, conversion of tryptophan to niacin, and may be involved in maintaining erythrocyte integrity.
Riboflavin functions as the coenzyme for flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which primarily influence hydrogen transport in oxidative enzyme systems (eg, cytochrome C reductase, succinic dehydrogenase, xanthine oxidase).
Two active forms of riboflavin exist ... coenzyme flavin mononucleotide (FMN) and coenzyme flavin adenine dinucleotide (FAD). They are formed by reaction of riboflavin with 1 and 2 molecules of ATP as follow: riboflavin + ATP = riboflavin-P (FMN) + ADP; FMN + ATP = riboflavin-ADP (FAD) + PP.
Riboflavin is a water-soluble, yellow, fluorescent compound. The primary form of the vitamin is as an integral component of the coenzymes flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). It is in these bound coenzyme forms that riboflavin functions as a catalyst for redox reactions in numerous metabolic pathways and in energy production. ... The redox reactions in which flavocoenzymes participate include flavoprotein-catalyzed dehydrogenations that are both pyridine nucleotide (niacin) dependent and independent, reactions with sulfur-containing compounds, hydroxylations, oxidative decarboxylations (involving thiamin as its pyrophosphate), dioxygenations, and reduction of oxygen to hydrogen peroxide. There are obligatory roles of flavocoenzymes in the formation of some vitamins and their coenzymes. For example, the biosynthesis of two niacin-containing coenzymes from tryptophan occurs via FAD-dependent kynurenine hydroxylase, an FMN-dependent oxidase catalyzes the conversion of the 5'-phosphates of vitamin B6 to coenzymic pyridoxal 5'-phosphate, and an FAD-dependent dehydrogenase reduces 5,10-methylene-tetrahydrofolate to the 5'-methyl product that interfaces with the B12-dependent formation of methionine from homocysteine and thus with sulfur amino acid metabolism.
For more Mechanism of Action (Complete) data for Riboflavin (7 total), please visit the HSDB record page.
Biological Half-Life
66-84 minutes
The biologic half-life of riboflavin is about 66-84 minutes following oral or IM administration of a single large dose in healthy individuals.
Metabolism/Metabolites
Hepatic.
Free riboflavin is converted in the intestinal mucosa into flavin mononucleotide which is transformed into flavin adenine dinucleotide in the liver.
The metabolism of riboflavin is a tightly controlled process that depends on the riboflavin status of the individual. Riboflavin is converted to coenzymes within the cellular cytoplasm of most tissues but mainly in the small intestine, liver, heart, and kidney. The metabolism of riboflavin begins with the adenosine triphosphate (ATP)-dependent phosphorylation of the vitamin to flavin mononucleotide (FMN). Flavokinase, the catalyst for this conversion, is under hormonal control. FMN can then be complexed with specific apoenzymes to form a variety of flavoproteins; however, most is converted to flavin-adenine dinucleotide (FAD) by FAD synthetase. As a result, FAD is the predominant flavocoenzyme in body tissues. Production of FAD is controlled by product inhibition such that an excess of FAD inhibits its further production.
The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. GTP is hydrolytically opened, converted into 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction and dephosphorylation. Condensation with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate leads to 6,7-dimethyl-8-ribityllumazine. The final step in the biosynthesis of the vitamin involves the dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin synthase. The mechanistically unusual reaction involves the transfer of a four-carbon fragment between two identical substrate molecules. The second product, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, is recycled in the biosynthetic pathway by 6,7-dimethyl-8-ribityllumazine synthase. This article will review structures and reaction mechanisms of riboflavin synthases and related proteins up to 2007 and 122 references are cited.
Hepatic. Half Life: 66-84 minutes
MeSH Pharmacological Classification
A group of water-soluble vitamins, some of which are COENZYMES.
Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms.
Absorption, Distribution and Excretion
Vitamin B2 is readily absorbed from the upper gastrointestinal tract.
Riboflavin is readily absorbed from the upper GI tract; however, absorption of the drug involves active transport mechanisms and the extent of GI absorption is limited by the duration of contact of the drug with the specialized segment of mucosa where absorption occurs. Riboflavin 5-phosphate is rapidly and almost completely dephosphorylated in the GI lumen before absorption occurs. The extent of GI absorption of riboflavin is increased when the drug is administered with food and is decreased in patients with hepatitis, cirrhosis, biliary obstruction, or in those receiving probenecid.
Primary absorption of riboflavin occurs in the small intestine via a rapid, saturable transport system. A small amount is absorbed in the large intestine. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. At low intake levels, most absorption of riboflavin occurs via an active or facilitated transport system. At higher levels of intake, riboflavin can be absorbed by passive diffusion.
In the plasma, a large portion of riboflavin associates with other proteins, mainly immunoglobulins, for transport. Pregnancy increases the level of carrier proteins available for riboflavin, which results in a higher rate of riboflavin uptake at the maternal surface of the placenta.
In the stomach, gastric acidification releases most of the coenzyme forms of riboflavin (flavin-adenine dinucleotide (FAD) and flavin mononucleotide (FMN)) from the protein. The noncovalently bound coenzymes are then hydrolyzed to riboflavin by nonspecific pyrophosphatases and phosphatases in the upper gut. Primary absorption of riboflavin occurs in the proximal small intestine via a rapid, saturable transport system. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. A small amount of riboflavin circulates via the enterohepatic system. At low intake levels most absorption of riboflavin is via an active or facilitated transport system.
For more Absorption, Distribution and Excretion (Complete) data for Riboflavin (16 total), please visit the HSDB record page.
Verwendung und Herstellung
Uses
Present in minute amounts in all plant and animal cells and especially in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables; Used as a food coloring and vitamin (enzyme cofactor); [Merck Index] Used as a medication, animal feed supplement, nutritional supplement, and to inactivate pathogens and viruses; [HSDB] Used as flavoring agent, color, and nutritional supplement for foods; [FDA] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]
Farming (Feed Additives) [Category: Industry]
Medicine, nutrition, animal feed supplement, enriched flours, dietary supplement
THERAPEUTIC CATEGORY: Vitamin (enzyme cofactor)
THERAPEUTIC CATEGORY (VETERINARY): Vitamin (enzyme cofactor)
Mirasol pathogen reduction technology (PRT) treatment uses riboflavin (vitamin B(2)) in combination with ultraviolet light (UV) to inactivate pathogens in platelet concentrates (PCs).
U.S. Exports
(1972) No data
(1975) No data
U.S. Imports
(1972) 7.24 X 10+7 g (Princpl Custms Dists)
(1975) 6.01 X 10+5 g (Princpl Custms Dists)
U.S. Production
(1972) 4.59 X 10+8 g
(1973) 3.35 X 10+8 g
Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#2209]
Methods of Manufacturing
The readily available compound 3,4-xylidine is reacted with D-ribose in methanol. The resulting riboside is catalytically hydrogenated to give N-(3,4-dimethylphenyl)-D-1'-ribamine without isolation, and the product is purified by crystallization. Coupling of /N-(3,4-dimethylphenyl)-D-1'-ribamine/ with phenyl diazonium salt in a buffered aqueous solution yields crystalline N-(2-phenylazo-4,5-dimethylphenyl)-D-1'-ribamine. Dry / N-(2-phenylazo-4,5-dimethylphenyl)-D-1'-ribamine/ is converted to riboflavin by cyclocondensation with barbituric acid in a weakly acidic medium. Mixtures of dioxane and acetic acid or di-alpha-substituted carboxylic acids have proved suitable as solvents. Crude /riboflavin/ can be purified by reprecipitation from hydrochloric acid or dilute sodium hydroxide solution, possibly with the addition of hydrogen peroxide.
Riboflavin can be produced microbiologically. At present, the microorganisms Bacillus subtilis, the ascomycetes Eremothecium ashbyii, Ashbya gossypii, and the yeasts Candida flareri and Saccharomyces cerevisiae are used. The nutrient media employed are molasses or plant oils as carbon source, inorganic salts, amino acids, animal or plant peptones and proteins, as well as vitamin additives. In a sterile aerobic submerged process, yields much higher than 10 grams of riboflavin per liter of culture broth are obtained in a few days with good aeration and stirring at temperatures below 30 °C. After separation of the biomass, evaporation and drying of the concentrate, an enriched product with a vitamin B2 content of up to 80% is obtained. The majority of the riboflavin produced by fermentation is used in animal feeds.
Condensation of d-ribose with 3,4-xylidine resulting in N-d -ribityl-3,4-xylidine, which is either coupled with a diazonium salt followed by reduction and reaction with alloxan, or reacted with barbituric acid; fermentation of carbohydrate materials by bacteria, yeast, or fungi
Use Classification
Food additives
Food Additives -> COLOUR -> JECFA Functional Classes
Food Additives -> COLOUR -> JECFA Functional Classes
Cosmetics -> Cosmetic colorant; Skin conditioning; Hair dyeing
General Manufacturing Information
Riboflavin: ACTIVE
The rumen microbial flora are a rich source of vitamins to the ruminant, and that the fecal bacterial flora are a major vitamin source for coprophagic rodents. There is also good evidence that the gut bacterial flora are a significant source of a range of vitamins to the human. In this paper evidence is presented that gut bacteria are a significant source of a range of vitamins, particularly those of the B group and vitamin K.
Recommended daily dietary allowance of Food and Nutrition Board ... is 0.4 to 0.6 mg for infants, 0.8 to 1.2 mg for children up to 10 yr, 1.2 to 2.8 mg for adolescents and adults, and slightly higher for women during pregnancy and lactation.
Minimal requirement for riboflavin to prevent clinical signs of deficiency appears to be less than 0.35 mg/1000 kcal.
... Widely distributed in nature, in ... plants and animals as an essential constituent of all living cells, and is therefore widely distributed in small amounts in foods.
Commercial ... distiller's residues (indirectly from dextrose, lactose, yeast, and whey)
Anwendungen
BeschreibungA water-soluble B fraction was found in the 1920s to contain a yellow, fluorescent growth factor called riboflavin in England and vitamin G in the United States. In the early 1930s, several groups found the coenzyme forms of riboflavin 50-phosphate (flavin mononucleotide) and the further conjugate with adenylic acid (flavin adenine dinucleotide).
Verwendenriboflavin (Vitamin B2) is used in skin care preparations as an emollient. It can be found in sun care products as a suntan enhancer. Medicinally, it is used for the treatment of skin lesions.
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Ergänzende Hinweise
DefinitionChEBI: 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 vege ables, 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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