T3DB: Riboflavin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2014-09-11 05:17:53 UTC

Update Date

2014-12-24 20:26:57 UTC

Accession Number

T3D4817

Identification

Common Name

Riboflavin

Class

Small Molecule

Description

Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form 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.

Compound Type

Amide
Drug
Food Toxin
Metabolite
Natural Compound
Nutraceutical
Organic Compound
Photosensitizing Agent
Plant Toxin
Vitamin B Complex

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(-)-Riboflavin
1-Deoxy-1-(3,4-dihydro-7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10(2H)-yl)-D-ribitol
1-Deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
6,7-Dimethyl-9-D-ribitylisoalloxazine
6,7-Dimethyl-9-ribitylisoalloxazine
7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)-Benzo[g]pteridine-2,4(3H,10H)-dione
7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4(3H,10H)-dione
7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)isoalloxazine
7,8-Dimethyl-10-ribitylisoalloxazine
Beflavin
Beflavine
Benzo[g]pteridine riboflavin deriv.
Bisulase
E 101
e101
Flavaxin
Flavin BB
Flaxain
Food Yellow 15
Hyre
Lactobene
Lactoflavin
Lactoflavine
Ribipca
Ribocrisina
Riboderm
Riboflavina
Riboflavine
Riboflavinum
Ribosyn
Ribotone
Ribovel
Russupteridine yellow III
San Yellow B
Vitaflavine
Vitamin B2
Vitamin G
Vitasan B2

Chemical Formula

C₁₇H₂₀N₄O₆

Average Molecular Mass

376.364 g/mol

Monoisotopic Mass

376.138 g/mol

CAS Registry Number

83-88-5

IUPAC Name

7,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-2H,3H,4H,10H-benzo[g]pteridine-2,4-dione

Traditional Name

riboflavin

SMILES

[H][C@@](O)(CO)[C@@]([H])(O)[C@@]([H])(O)CN1C2=C(C=C(C)C(C)=C2)N=C2C(O)=NC(=O)N=C12

InChI Identifier

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

InChI Key

InChIKey=AUNGANRZJHBGPY-SCRDCRAPSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as flavins. Flavins are compounds containing a flavin (7,8-dimethyl-benzo[g]pteridine-2,4-dione) moiety, with a structure characterized by an isoalloaxzine tricyclic ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Pteridines and derivatives

Sub Class

Alloxazines and isoalloxazines

Direct Parent

Flavins

Alternative Parents

Substituents

Flavin
Diazanaphthalene
Quinoxaline
Pyrimidone
Pyrazine
Pyrimidine
Benzenoid
Heteroaromatic compound
Vinylogous amide
Secondary alcohol
Lactam
Polyol
Azacycle
Alcohol
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organic oxygen compound
Primary alcohol
Organooxygen compound
Organonitrogen compound
Organic nitrogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

flavin (CHEBI:17015 )
Water-soluble vitamins (C00255 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Erythrocyte
Heart
Kidney
Liver
Prostate

Pathways

Name	SMPDB Link	KEGG Link
Riboflavin Metabolism	SMP00070	map00740

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	280 dec°C
Boiling Point	Not Available
Solubility	84.7 mg/L (at 25°C)
LogP	-1.46

Predicted Properties

Property	Value	Source
Water Solubility	0.66 g/L	ALOGPS
logP	-1	ALOGPS
logP	-0.92	ChemAxon
logS	-2.8	ALOGPS
pKa (Strongest Acidic)	5.97	ChemAxon
pKa (Strongest Basic)	-2.6	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	9	ChemAxon
Hydrogen Donor Count	5	ChemAxon
Polar Surface Area	155.05 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	96.27 m³·mol⁻¹	ChemAxon
Polarizability	37.51 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-006x-4980000000-dd278a577316361d270a	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-006x-4980000000-dd278a577316361d270a	2018-05-18	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0btc-9014000000-75f046dc3c6cb008690e	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (4 TMS) - 70eV, Positive	splash10-0zfs-5146149000-f9db57dd1ccd4a014604	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_3) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_4) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_3_5) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-0a4i-0091000000-a82c54d3153103fcdb1f	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-0a4i-0091000000-a82c54d3153103fcdb1f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-0a4i-0090000000-2aff124ee1fc62c13844	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-0a4i-0090000000-f8b29c3e2c601a944a6c	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-0a4i-0090000000-4e8c9bd38ea0f5ae9a94	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-0090000000-5288e9226616bb75603c	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0093000000-5999e10d04a53f4dae9b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-0091000000-8f391045e25f26d53384	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-08fv-0290000000-b4d5f66b726c01d08c55	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-0006-4690000000-d195fd5aee22ece7f2ec	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0039000000-549fbc0a59262f64680e	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0195000000-58354696aaddaffc0fd8	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-0f76-9231000000-67715e21d6e9ce2655fe	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0a4i-0090000000-838afb0228d293bee0a3	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-2190000000-b659be001c9aa265c257	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0a4i-0090000000-21473bfb7f4a3eafd059	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-004i-0019000000-86365dedafa031aa7787	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0006-4390000000-ac1b59ab7cc2209f4241	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-00dj-4900000000-72d33eb27b9bd6a13d9e	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-004l-0569000000-874b71fdc78d04853bf0	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-004i-0239000000-659ca9fae9643f3ce73d	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004l-0569000000-874b71fdc78d04853bf0	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , positive	splash10-0006-0092000000-1f1be5508c1d50d8dff7	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , positive	splash10-0006-0092000000-74bf0b86efe72fe37198	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , positive	splash10-057i-0069000000-bb0522be4472e049dbc5	2017-09-14	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)	Not Available	2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-29	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Vitamin B2 is readily absorbed from the upper gastrointestinal tract.

Mechanism of Toxicity

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.

Metabolism

Hepatic. Half Life: 66-84 minutes

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of ariboflavinosis (vitamin B2 deficiency).

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

17015

BioCyc ID

RIBOFLAVIN

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

RBF

ACToR ID

Not Available

Wikipedia Link

Riboflavin

References

Synthesis Reference

Hansgeorg Ernst, Wolfram Schmidt, Joachim Paust, “Preparation of riboflavin.” U.S. Patent US4567261, issued August, 1958.

MSDS

Link

General References

Zempleni 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. [8604671 ]
Mathew 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. [12354259 ]
Booth 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. [9808225 ]
Boisvert 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. [8487103 ]
Mikalunas 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. [11606856 ]
Belko 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. [6475825 ]
Alexander 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. [6546833 ]
Baeckert 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. [3142982 ]
Maiani 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. [6650303 ]
Bamji 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. [3592624 ]
Ajayi OA: Bioavailability of riboflavin from fortified palm juice. Plant Foods Hum Nutr. 1989 Dec;39(4):375-80. [2631092 ]
Kodentsova 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. [8678471 ]
Bates 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. [4019261 ]
Brun 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. [2369885 ]
Mulherin 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. [8976642 ]
Rao 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. [10566553 ]
Zhou 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. [14963913 ]
Thurnham 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. [3878498 ]
Bates 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. [7101408 ]
Dror 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. [7883462 ]
Switzer 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. [9184778 ]
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: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Riboflavin kinase

General Function:: Riboflavin kinase activity
Specific Function:: Catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin-mononucleotide (FMN), hence rate-limiting enzyme in the synthesis of FAD. Essential for TNF-induced reactive oxygen species (ROS) production. Through its interaction with both TNFRSF1A and CYBA, physically and functionally couples TNFRSF1A to NADPH oxidase. TNF-activation of RFK may enhance the incorporation of FAD in NADPH oxidase, a critical step for the assembly and activation of NADPH oxidase.
Gene Name:: RFK
Uniprot ID:: Q969G6
Molecular Weight:: 17623.08 Da

References

Werner R, Manthey KC, Griffin JB, Zempleni J: HepG2 cells develop signs of riboflavin deficiency within 4 days of culture in riboflavin-deficient medium. J Nutr Biochem. 2005 Oct;16(10):617-24. [16081269 ]
Solovieva IM, Kreneva RA, Errais Lopes L, Perumov DA: The riboflavin kinase encoding gene ribR of Bacillus subtilis is a part of a 10 kb operon, which is negatively regulated by the yrzC gene product. FEMS Microbiol Lett. 2005 Feb 1;243(1):51-8. [15668000 ]
Ishchuk OP, Iatsyshyn VIu, Dmytruk KV, Voronovs'kyi AIa, Fedorovych DV, Sybirnyi AA: [Construction of the flavinogenic yeast Candida famata strains with high riboflavin kinase activity using gene engineering]. Ukr Biokhim Zh. 2006 Sep-Oct;78(5):63-9. [17290783 ]
Sandoval FJ, Roje S: An FMN hydrolase is fused to a riboflavin kinase homolog in plants. J Biol Chem. 2005 Nov 18;280(46):38337-45. Epub 2005 Sep 23. [16183635 ]
Bertollo CM, Oliveira AC, Rocha LT, Costa KA, Nascimento EB Jr, Coelho MM: Characterization of the antinociceptive and anti-inflammatory activities of riboflavin in different experimental models. Eur J Pharmacol. 2006 Oct 10;547(1-3):184-91. Epub 2006 Jul 26. [16962092 ]
Hirano G, Izumi H, Yasuniwa Y, Shimajiri S, Ke-Yong W, Sasagiri Y, Kusaba H, Matsumoto K, Hasegawa T, Akimoto M, Akashi K, Kohno K: Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin. Int J Oncol. 2011 Apr;38(4):893-902. doi: 10.3892/ijo.2011.938. Epub 2011 Feb 9. [21308351 ]

Target Details

2. Flavin reductase (NADPH)

General Function:: Riboflavin reductase (nadph) activity
Specific Function:: Broad specificity oxidoreductase that catalyzes the NADPH-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to heme catabolism and metabolizes linear tetrapyrroles. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin.
Gene Name:: BLVRB
Uniprot ID:: P30043
Molecular Weight:: 22119.215 Da

References

Russell TR, Demeler B, Tu SC: Kinetic mechanism and quaternary structure of Aminobacter aminovorans NADH:flavin oxidoreductase: an unusual flavin reductase with bound flavin. Biochemistry. 2004 Feb 17;43(6):1580-90. [14769034 ]
van Pee KH, Patallo EP: Flavin-dependent halogenases involved in secondary metabolism in bacteria. Appl Microbiol Biotechnol. 2006 May;70(6):631-41. Epub 2006 Mar 17. [16544142 ]

Target Details

3. Androgen receptor

General Function:: Zinc ion binding
Specific Function:: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:: AR
Uniprot ID:: P10275
Molecular Weight:: 98987.9 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.03 uM	NVS_NR_hAR	Novascreen

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

4. Retinoic acid receptor alpha

General Function:: Zinc ion binding
Specific Function:: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
Gene Name:: RARA
Uniprot ID:: P10276
Molecular Weight:: 50770.805 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	7.11 uM	NVS_NR_hRARa_Agonist	Novascreen

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Riboflavin (T3D4817)

Structure for T3D4817: Riboflavin

Targets

References

References

Binding/Activity Constants

References

Binding/Activity Constants

References