2.02012-05-31 10:24:45 -06002015-09-13 12:56:07 -0600ECMDB00244M2MDB000103RiboflavinRiboflavin, also known as vitamin B2, is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a wide variety of cellular processes. Like the other B vitamins, it plays a key role in energy metabolism, and is required for the metabolism of fats, ketone bodies, carbohydrates, and proteins. (Wikipedia)(-)-Riboflavin1-Deoxy-1-(3,4-dihydro-7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10(2H)-yl)-D-ribitol6,7-Dimethyl-9-D-ribitylisoalloxazine6,7-Dimethyl-9-ribitylisoalloxazine7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)-Benzo[g]pteridine-2,4(3H,10H)-dioneBeflavinBeflavineBenzo[g]pteridine riboflavin deriv.E 101FlavaxinFlavin BBFlaxainFood Yellow 15HyreLactobeneLactoflavinLactoflavineRibipcaRibocrisinaRibodermRiboflavineRibosynRibotoneRibovelRussupteridine yellow IRussupteridine yellow IIISan Yellow BVitaflavineVitamin B2Vitamin B<sub>2</sub>Vitamin GVitasan B2C17H20N4O6376.3639376.1382843927,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-2H,3H,4H,10H-benzo[g]pteridine-2,4-dioneriboflavin83-88-5CC1=C(C)C=C2N(C[C@H](O)[C@H](O)[C@H](O)CO)C3=NC(=O)NC(=O)C3=NC2=C1InChI=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/s1AUNGANRZJHBGPY-SCRDCRAPSA-NSolidCytosollogp-1.05logs-2.76solubility6.57e-01 g/lmelting_point290 oClogp-0.92pka_strongest_acidic5.97pka_strongest_basic-2.6iupac7,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-2H,3H,4H,10H-benzo[g]pteridine-2,4-dioneaverage_mass376.3639mono_mass376.138284392smilesCC1=C(C)C=C2N(C[C@H](O)[C@H](O)[C@H](O)CO)C3=NC(=O)NC(=O)C3=NC2=C1formulaC17H20N4O6inchiInChI=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/s1inchikeyAUNGANRZJHBGPY-SCRDCRAPSA-Npolar_surface_area155.05refractivity96.27polarizability37.51rotatable_bond_count5acceptor_count9donor_count5physiological_charge-1formal_charge0Riboflavin metabolismec00740Metabolic pathwayseco01100Flavin biosynthesisThe process of flavin biosynthesis starts with GTP being metabolized by interacting with 3 molecules of water through a GTP cyclohydrolase resulting in a release of formic acid, a pyrophosphate, two hydrog ions and 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one or 2,5-Diamino-6-hydroxy-4-(5-phosphoribosylamino)pyrimidine. Either of these compounds interacts with a water molecule and a hydrogen ion through a fused diaminohydroxyphosphoribosylaminopyrimidine deaminase / 5-amino-6-(5-phosphoribosylamino)uracil reductase resulting in an ammonium and 5-amino-6-(5-phospho-D-ribosylamino)uracil. This compound then interacts with a hydrogen ion through a NADPH dependent fused diaminohydroxyphosphoribosylaminopyrimidine deaminase / 5-amino-6-(5-phosphoribosylamino)uracil reductase resulting in the release of a NADP and a 5-amino-6-(5-phospho-D-ribitylamino)uracil. This compound then interacts with a water molecule through a 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase resulting in a release of a phosphate, and a 5-amino-6-(D-ribitylamino)uracil.
D-ribulose 5-phosphate interacts with a3,4-dihydroxy-2-butanone 4-phosphate synthase resulting in the release of formic acid, a hydrogen ion and 1-deoxy-L-glycero-tetrulose 4-phosphate.
A 5-amino-6-(D-ribitylamino)uracil and 1-deoxy-L-glycero-tetrulose 4-phosphate interact through a 6,7-dimethyl-8-ribityllumazine synthase resulting in the release of 2 water molecules, a phosphate, a hydrogen ion and a 6,7-dimethyl-8-(1-D-ribityl)lumazine.
The latter compound then interacts with a hydrogen ion through a riboflavin synthase resulting in the release of a riboflavin and a 5-amino-6-(d-ribitylamino)uracil.
The riboflavin is then phosphorylated through an ATP dependent riboflavin kinase resulting in the release of a ADP, a hydrogen ion and a FLAVIN MONONUCLEOTIDE.
The flavin mononucleotide interad with a hydrogen ion and an ATP through the riboflavin kinase resulting in the release of a pyrophosphate and Flavin Adenine dinucleotide. This compound is then exported into the periplasm through a FMN/FAD exporter.
PW001971Metabolicflavin biosynthesis I (bacteria and plants)RIBOSYN2-PWYSpecdb::CMs10276Specdb::CMs29895Specdb::CMs37383Specdb::CMs99553Specdb::CMs148319Specdb::CMs1055182Specdb::CMs1055183Specdb::CMs1055185Specdb::CMs1055187Specdb::CMs1055189Specdb::CMs1055191Specdb::CMs1055193Specdb::CMs1055195Specdb::CMs1055197Specdb::CMs1055199Specdb::CMs1055201Specdb::CMs1055203Specdb::CMs1055205Specdb::CMs1055206Specdb::CMs1055208Specdb::CMs1055210Specdb::CMs1055212Specdb::CMs1055214Specdb::CMs1055216Specdb::CMs1055218Specdb::NmrOneD1268Specdb::NmrOneD143170Specdb::NmrOneD143171Specdb::NmrOneD143172Specdb::NmrOneD143173Specdb::NmrOneD143174Specdb::NmrOneD143175Specdb::NmrOneD143176Specdb::NmrOneD143177Specdb::NmrOneD143178Specdb::NmrOneD143179Specdb::NmrOneD143180Specdb::NmrOneD143181Specdb::NmrOneD143182Specdb::NmrOneD143183Specdb::NmrOneD143184Specdb::NmrOneD143185Specdb::NmrOneD143186Specdb::NmrOneD143187Specdb::NmrOneD143188Specdb::NmrOneD143189Specdb::MsMs3737Specdb::MsMs439241Specdb::MsMs439535Specdb::MsMs439536Specdb::MsMs439733Specdb::MsMs2226570Specdb::MsMs2231229Specdb::MsMs2231301Specdb::MsMs2232918Specdb::MsMs2232951Specdb::MsMs2233613Specdb::MsMs2233669Specdb::MsMs2235291Specdb::MsMs2235304Specdb::MsMs2252521Specdb::MsMs2253947Specdb::MsMs412Specdb::MsMs413Specdb::MsMs414Specdb::MsMs3736Specdb::MsMs374336Specdb::MsMs448178Specdb::MsMs449588Specdb::MsMs449589Specdb::MsMs449590Specdb::NmrTwoD1234HMDB002446759431981C0025517015RIBOFLAVINRBFRiboflavinKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Sreekumar 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: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.19212411Mathew JL, Kabi BC, Rath B: Anti-oxidant vitamins and steroid responsive nephrotic syndrome in Indian children. J Paediatr Child Health. 2002 Oct;38(5):450-37.12354259Booth CK, Clark T, Fenn A: Folic acid, riboflavin, thiamine, and vitamin B-6 status of a group of first-time blood donors. Am J Clin Nutr. 1998 Nov;68(5):1075-80.9808225Boisvert WA, Mendoza I, Castaneda C, De Portocarrero L, Solomons NW, Gershoff SN, Russell RM: Riboflavin requirement of healthy elderly humans and its relationship to macronutrient composition of the diet. J Nutr. 1993 May;123(5):915-25.8487103Mikalunas V, Fitzgerald K, Rubin H, McCarthy R, Craig RM: Abnormal vitamin levels in patients receiving home total parenteral nutrition. J Clin Gastroenterol. 2001 Nov-Dec;33(5):393-6.11606856Belko AZ, Obarzanek E, Roach R, Rotter M, Urban G, Weinberg S, Roe DA: Effects of aerobic exercise and weight loss on riboflavin requirements of moderately obese, marginally deficient young women. Am J Clin Nutr. 1984 Sep;40(3):553-61.6475825Alexander M, Emanuel G, Golin T, Pinto JT, Rivlin RS: Relation of riboflavin nutriture in healthy elderly to intake of calcium and vitamin supplements: evidence against riboflavin supplementation. Am J Clin Nutr. 1984 Apr;39(4):540-6.6546833Baeckert PA, Greene HL, Fritz I, Oelberg DG, Adcock EW: Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin. J Pediatr. 1988 Dec;113(6):1057-65.3142982Maiani G, Mobarhan S, Nicastro A, Virgili F, Scaccini C, Ferro-Luzzi A: [Determination of glutathione reductase activity in erythrocytes and whole blood as an indicator of riboflavin nutrition] Acta Vitaminol Enzymol. 1983;5(3):171-8.6650303Bamji MS, Bhaskaram P, Jacob CM: Urinary riboflavin excretion and erythrocyte glutathione reductase activity in preschool children suffering from upper respiratory infections and measles. Ann Nutr Metab. 1987;31(3):191-6.3592624Ajayi OA: Bioavailability of riboflavin from fortified palm juice. Plant Foods Hum Nutr. 1989 Dec;39(4):375-80.2631092Kodentsova VM, Vrzhesinskaya OA, Spirichev VB: Fluorometric riboflavin titration in plasma by riboflavin-binding apoprotein as a method for vitamin B2 status assessment. Ann Nutr Metab. 1995;39(6):355-60.8678471Bates CJ, Powers HJ: A simple fluorimetric assay for pyridoxamine phosphate oxidase in erythrocyte haemolysates: effects of riboflavin supplementation and of glucose 6-phosphate dehydrogenase deficiency. Hum Nutr Clin Nutr. 1985 Mar;39(2):107-15.4019261Brun TA, Chen J, Campbell TC, Boreham J, Feng Z, Parpia B, Shen TF, Li M: Urinary riboflavin excretion after a load test in rural China as a measure of possible riboflavin deficiency. Eur J Clin Nutr. 1990 Mar;44(3):195-206.2369885Mulherin DM, Thurnham DI, Situnayake RD: Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis. Ann Rheum Dis. 1996 Nov;55(11):837-40.8976642Rao PN, Levine E, Myers MO, Prakash V, Watson J, Stolier A, Kopicko JJ, Kissinger P, Raj SG, Raj MH: Elevation of serum riboflavin carrier protein in breast cancer. Cancer Epidemiol Biomarkers Prev. 1999 Nov;8(11):985-90.10566553Zhou X, Huang C, Hong J, Yao S: [Nested case-control study on riboflavin levels in blood and urine and the risk of lung cancer] Wei Sheng Yan Jiu. 2003 Nov;32(6):597-8, 601.14963913Thurnham DI, Zheng SF, Munoz N, Crespi M, Grassi A, Hambidge KM, Chai TF: Comparison of riboflavin, vitamin A, and zinc status of Chinese populations at high and low risk for esophageal cancer. Nutr Cancer. 1985;7(3):131-43.3878498Bates CJ, Prentice AM, Paul AA, Prentice A, Sutcliffe BA, Whitehead RG: Riboflavin status in infants born in rural Gambia, and the effect of a weaning food supplement. Trans R Soc Trop Med Hyg. 1982;76(2):253-8.7101408Dror Y, Stern F, Komarnitsky M: Optimal and stable conditions for the determination of erythrocyte glutathione reductase activation coefficient to evaluate riboflavin status. Int J Vitam Nutr Res. 1994;64(4):257-62.7883462Switzer BR, Stark AH, Atwood JR, Ritenbaugh C, Travis RG, Wu HM: Development of a urinary riboflavin adherence marker for a wheat bran fiber community intervention trial. Cancer Epidemiol Biomarkers Prev. 1997 Jun;6(6):439-42.9184778Zempleni J, Galloway JR, McCormick DB: Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans. Am J Clin Nutr. 1996 Jan;63(1):54-66.8604671Tishler, Max; Pfister, Karl, III; Babson, R. D.; Ladenburg, Kurt; Fleming, Ann J. Reaction between o-aminoazo compounds and barbituric acid. A new synthesis of riboflavin. Journal of the American Chemical Society (1947), 69 1487-92.http://hmdb.ca/system/metabolites/msds/000/000/178/original/HMDB00244.pdf?1358895546Periplasmic AppA proteinP07102PPA_ECOLIappAhttp://ecmdb.ca/proteins/P07102.xmlClass B acid phosphataseP0AE22APHA_ECOLIaphAhttp://ecmdb.ca/proteins/P0AE22.xmlNAD(P)H-flavin reductaseP0AEN1FRE_ECOLIfrehttp://ecmdb.ca/proteins/P0AEN1.xmlRiboflavin synthase alpha chainP0AFU8RISA_ECOLIribEhttp://ecmdb.ca/proteins/P0AFU8.xmlRiboflavin biosynthesis protein ribFP0AG40RIBF_ECOLIribFhttp://ecmdb.ca/proteins/P0AG40.xmlSulfite reductase [NADPH] hemoprotein beta-componentP17846CYSI_ECOLIcysIhttp://ecmdb.ca/proteins/P17846.xmlSulfite reductase [NADPH] flavoprotein alpha-componentP38038CYSJ_ECOLIcysJhttp://ecmdb.ca/proteins/P38038.xmlFerric iron reductase protein fhuFP39405FHUF_ECOLIfhuFhttp://ecmdb.ca/proteins/P39405.xml6,7-dimethyl-8-ribityllumazine synthaseP61714RISB_ECOLIribHhttp://ecmdb.ca/proteins/P61714.xmlPhosphatase ybjIP75809YBJI_ECOLIybjIhttp://ecmdb.ca/proteins/P75809.xmlHydrogen ion + NADPH + Riboflavin > NADP + Reduced riboflavinNADPH-DEHYDROGENASE-FLAVIN-RXNAdenosine triphosphate + Riboflavin <> ADP + Flavin Mononucleotide + Hydrogen ionR00549RIBOFLAVINKIN-RXN2 6,7-Dimethyl-8-(1-D-ribityl)lumazine > 5-Amino-6-ribitylamino uracil + RiboflavinR00066Hydrogen ion + NADH + Riboflavin > NAD + Reduced riboflavin2 Ferroxamine + Reduced riboflavin >2 Iron +2 ferroxamine minus Fe(3) +2 Hydrogen ion + Riboflavin2 6,7-Dimethyl-8-(1-D-ribityl)lumazine <> Riboflavin + 5-Amino-6-ribitylamino uracilR00066Flavin Mononucleotide + Water <> Riboflavin + PhosphateR00548RXN0-5187Adenosine triphosphate + Riboflavin <> ADP + Flavin MononucleotideR00549Reduced riboflavin + NADP < Hydrogen ion + Riboflavin + NADPHNADPH-DEHYDROGENASE-FLAVIN-RXNHydrogen ion + 6,7-Dimethyl-8-(1-D-ribityl)lumazine > 5-amino-6-(D-ribitylamino)uracil + RiboflavinRIBOFLAVIN-SYN-RXNRiboflavin + Adenosine triphosphate > Hydrogen ion + Flavin Mononucleotide + ADPRIBOFLAVINKIN-RXNReduced riboflavin + NAD(P)<sup>+</sup> Riboflavin + NAD(P)H + Hydrogen ionRXN-12445Flavin Mononucleotide + Water > Riboflavin + PhosphateRXN0-5187Reduced riboflavin + NAD(P)(+) > Riboflavin + NAD(P)HAdenosine triphosphate + Riboflavin > ADP + Flavin Mononucleotide2 6,7-dimethyl-8-(D-ribityl)lumazine > Riboflavin + 5-amino-6-ribitylamino-2,4(1h,3h)-pyrimidinedione6,7-Dimethyl-8-(1-D-ribityl)lumazine + Hydrogen ion + 6,7-Dimethyl-8-(1-D-ribityl)lumazine > Riboflavin + 5-Amino-6-ribitylamino uracil + RiboflavinPW_R005563Riboflavin + Adenosine triphosphate + Riboflavin > Adenosine diphosphate + Hydrogen ion + Flavin Mononucleotide + ADPPW_R005564Riboflavin + NADPH + 2 Hydrogen ion > Riboflavin reduced + NADPPW_R0059142 6,7-Dimethyl-8-(1-D-ribityl)lumazine >5 5-Amino-6-ribitylamino uracil + RiboflavinAdenosine triphosphate + Riboflavin <> ADP + Flavin Mononucleotide + Hydrogen ionGutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucoseShake flask and filter culture19.0uM0.037 oCK12 NCM3722Mid-Log Phase760000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerolShake flask and filter culture22.1uM0.037 oCK12 NCM3722Mid-Log Phase884000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetateShake flask and filter culture18.8uM0.037 oCK12 NCM3722Mid-Log Phase752000Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599.19561621