Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:24:30 UTC
HMDB IDHMDB00030
Secondary Accession NumbersNone
Metabolite Identification
Common NameBiotin
DescriptionBiotin is an enzyme co-factor present in minute amounts in every living cell. Biotin is also known as vitamin H or B7 or coenzyme R. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk. Biotin has been recognized as an essential nutrient. Our biotin requirement is fulfilled in part through diet, through endogenous reutilization of biotin and perhaps through capture of biotin generated in the intestinal flora. The utilization of biotin for covalent attachment to carboxylases and its reutilization through the release of carboxylase biotin after proteolytic degradation constitutes the 'biotin cycle'. Biotin deficiency is associated with neurological manifestations, skin rash, hair loss and metabolic disturbances that are thought to relate to the various carboxylase deficiencies (metabolic ketoacidosis with lactic acidosis). It has also been suggested that biotin deficiency is associated with protein malnutrition, and that marginal biotin deficiency in pregnant women may be teratogenic. Biotin acts as a carboxyl carrier in carboxylation reactions. There are four biotin-dependent carboxylases in mammals: those of propionyl-CoA (PCC), 3-methylcrotonyl-CoA (MCC), pyruvate (PC) and acetyl-CoA carboxylases (isoforms ACC-1 and ACC-2). All but ACC-2 are mitochondrial enzymes. The biotin moiety is covalently bound to the epsilon amino group of a Lysine residue in each of these carboxylases in a domain 60-80 amino acids long. The domain is structurally similar among carboxylases from bacteria to mammals. There are four biotin-dependent carboxylases in mammals: those of propionyl-CoA (PCC), 3-methylcrotonyl-CoA (MCC), pyruvate (PC) and acetyl-CoA carboxylases (isoforms ACC-1 and ACC-2). All but ACC-2 are mitochondrial enzymes. The biotin moiety is covalently bound to the epsilon amino group of a Lys residue in each of these carboxylases in a domain 60-80 amino acids long. The domain is structurally similar among carboxylases from bacteria to mammals. Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have been identified in various human tissues. Many biotin-dependent gene products play roles in signal transduction and localize to the cell nucleus, consistent with a role for biotin in cell signaling. Posttranscriptional events related to ribosomal activity and protein folding may further contribute to effects of biotin on gene expression. Finally, research has shown that biotinidase and holocarboxylase synthetase mediate covalent binding of biotin to histones (DNA-binding proteins), affecting chromatin structure; at least seven biotinylation sites have been identified in human histones. Biotinylation of histones appears to play a role in cell proliferation, gene silencing, and the cellular response to DNA repair. Roles for biotin in cell signaling and chromatin structure are consistent with the notion that biotin has a unique significance in cell biology. (PMID: 15992684 , 16011464 ).
Structure
Thumb
Synonyms
  1. (+)-Biotin
  2. (+)-cis-Hexahydro-2-oxo-1H-thieno[3,4]imidazole-4-valerate
  3. (+)-cis-Hexahydro-2-oxo-1H-thieno[3,4]imidazole-4-valeric acid
  4. (3aS,4S,6aR)-Hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-valerate
  5. (3aS,4S,6aR)-Hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-valeric acid
  6. -(+)-biotin
  7. 1swk
  8. 1swn
  9. 1swr
  10. 5-(2-Oxohexahydro-1H-thieno[3,4-D]imidazol-4-yl)pentanoate
  11. 5-(2-Oxohexahydro-1H-thieno[3,4-D]imidazol-4-yl)pentanoic acid
  12. Biodermatin
  13. Bioepiderm
  14. Bios h
  15. Bios II
  16. Biotin
  17. cis-(+)-Tetrahydro-2-oxothieno[3,4]imidazoline-4-valerate
  18. cis-(+)-Tetrahydro-2-oxothieno[3,4]imidazoline-4-valeric acid
  19. cis-Hexahydro-2-oxo-1H-thieno(3,4)imidazole-4-valeric acid
  20. cis-Tetrahydro-2-oxothieno(3,4-D)imidazoline-4-valeric acid
  21. Coenzyme R
  22. D(+)-Biotin
  23. D-(+)-Biotin
  24. D-Biotin
  25. D-Biotin factor S
  26. delta-(+)-Biotin
  27. delta-Biotin
  28. delta-Biotin factor S
  29. Factor S
  30. Factor S (vitamin)
  31. Hexahydro-2-oxo-1H-thieno(3,4-D)imidazole-4-pentanoate
  32. Hexahydro-2-oxo-1H-thieno(3,4-D)imidazole-4-pentanoic acid
  33. Hexahydro-2-oxo-[3aS-(3aa,4b,6aa)]-1H-Thieno[3,4-D]imidazole-4-pentanoate
  34. Hexahydro-2-oxo-[3aS-(3aa,4b,6aa)]-1H-Thieno[3,4-D]imidazole-4-pentanoic acid
  35. Hexahydro-2-oxo-[3as-(3alpha,4beta,6alpha)]-1H-Thieno[3,4-D]imidazole-4-pentanoate
  36. Hexahydro-2-oxo-[3as-(3alpha,4beta,6alpha)]-1H-Thieno[3,4-D]imidazole-4-pentanoic acid
  37. Lutavit H2
  38. Meribin
  39. Rovimix H 2
  40. Vitamin B7
  41. Vitamin H
  42. Vitamin-h
Chemical FormulaC10H16N2O3S
Average Molecular Weight244.311
Monoisotopic Molecular Weight244.088163078
IUPAC Name5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl]pentanoic acid
Traditional IUPAC Namebiotin
CAS Registry Number58-85-5
SMILES
[H][C@]12CS[C@@H](CCCCC(O)=O)[C@@]1([H])NC(=O)N2
InChI Identifier
InChI=1S/C10H16N2O3S/c13-8(14)4-2-1-3-7-9-6(5-16-7)11-10(15)12-9/h6-7,9H,1-5H2,(H,13,14)(H2,11,12,15)/t6-,7-,9-/m0/s1
InChI KeyYBJHBAHKTGYVGT-ZKWXMUAHSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAliphatic Heteropolycyclic Compounds
ClassThienoimidazolidines
Sub ClassBiotin and Derivatives
Other Descriptors
  • Aliphatic Heteropolycyclic Compounds
  • Heterocyclic Fatty Acids
  • Thia Fatty Acids
Substituents
  • Carboxylic Acid
  • Imidazolidine
  • Imidazolidinone
  • Thioether
  • Thiolane
  • Urea
Direct ParentBiotin and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Food
Biofunction
  • Component of Biotin metabolism
  • Essential vitamins
Application
  • .
Cellular locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Nucleus
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point232 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.22 mg/mL at 25 °CNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility1.22 g/LALOGPS
logP0.17ALOGPS
logP0.32ChemAxon
logS-2.3ALOGPS
pKa (strongest acidic)4.4ChemAxon
pKa (strongest basic)-1.9ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count3ChemAxon
polar surface area78.43ChemAxon
rotatable bond count5ChemAxon
refractivity60.05ChemAxon
polarizability24.92ChemAxon
Spectra
Spectra
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Nucleus
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • All Tissues
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Biotin MetabolismSMP00066map00780
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified0.0034 (0.002 - 0.0051) uMNewborn (0-30 days old)BothNormal
  • Geigy Scient...
BloodDetected and Quantified0.0016 (0.0009 - 0.0028) uMChildren (1-13 year old)Not SpecifiedNormal
  • Geigy Scient...
BloodDetected and Quantified0.0024 (0.0008 - 0.0041) uMAdult (>18 years old)FemaleNormal
  • Geigy Scient...
BloodDetected and Quantified0.00127 +/- 0.00067 uMAdult (>18 years old)BothNormal
Cerebrospinal Fluid (CSF)Detected and Quantified0.000557 +/- 0.000307 uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified0.0005 +/- 0.0002 uMAdult (>18 years old)Not SpecifiedNormal
UrineDetected and Quantified0.014 (0.002-0.044) umol/mmol creatinineChildren (1-13 year old)BothNormal
  • Geigy Scient...
UrineDetected and Quantified0.049 +/- 0.035 umol/mmol creatinineAdult (>18 years old)BothNormal
UrineDetected and Quantified0.023 (0.013-0.032) umol/mmol creatinineAdult (>18 years old)BothNormal
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReference
Cerebrospinal Fluid (CSF)Detected and Quantified0.08198 (0.00033-0.421) uMNot SpecifiedNot Specifiedacute lymphoblastic leukemia
Cerebrospinal Fluid (CSF)Detected and Quantified0.16 uMNot SpecifiedNot SpecifiedBronchopulmonary dysplasia
Cerebrospinal Fluid (CSF)Detected and Quantified0.00039 uMNot SpecifiedNot SpecifiedBurkitt's lymphoma
Cerebrospinal Fluid (CSF)Detected and Quantified0.000447 +/- 0.000217 uMNot SpecifiedNot SpecifiedDementia
Cerebrospinal Fluid (CSF)Detected and Quantified0.000336 +/- 8.603e-05 uMNot SpecifiedNot SpecifiedEpilepsy
Cerebrospinal Fluid (CSF)Detected and Quantified0.0229 uMNot SpecifiedNot SpecifiedHead injury
Cerebrospinal Fluid (CSF)Detected and Quantified0.0273 (0.0247-0.0299) uMNot SpecifiedNot SpecifiedLymphoblastic lymphoma
Cerebrospinal Fluid (CSF)Detected and Quantified0.000459 +/- 9.0000e-05 uMNot SpecifiedNot SpecifiedMotor Neuron disease
Cerebrospinal Fluid (CSF)Detected and Quantified0.000324 +/- 0.000107 uMNot SpecifiedNot SpecifiedMultiple sclerosis
Cerebrospinal Fluid (CSF)Detected and Quantified0.000692 +/- 0.000602 uMNot SpecifiedNot SpecifiedPolyneuropathy
Cerebrospinal Fluid (CSF)Detected and Quantified0.000438 +/- 0.000156 uMNot SpecifiedNot SpecifiedVascular encephalopathies
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00121
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB014510
KNApSAcK IDC00000756
Chemspider ID149962
KEGG Compound IDC00120
BioCyc IDBIOTIN
BiGG ID33931
Wikipedia LinkBiotin
NuGOwiki LinkHMDB00030
Metagene LinkHMDB00030
METLIN ID243
PubChem Compound171548
PDB IDBTN
ChEBI ID15956
References
Synthesis ReferenceCorey, E. J.; Mehrotra, Mukund M. A simple and enantioselective synthesis of (+)-biotin. Tetrahedron Letters (1988), 29(1), 57-60.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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. Pubmed: 19212411
  2. Thuy LP, Belmont J, Nyhan WL: Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. Prenat Diagn. 1999 Feb;19(2):108-12. Pubmed: 10215065
  3. Zempleni J, McCormick DB, Mock DM: Identification of biotin sulfone, bisnorbiotin methyl ketone, and tetranorbiotin-l-sulfoxide in human urine. Am J Clin Nutr. 1997 Feb;65(2):508-11. Pubmed: 9022537
  4. Bussolati G, Gugliotta P, Volante M, Pace M, Papotti M: Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry. Histopathology. 1997 Nov;31(5):400-7. Pubmed: 9416479
  5. Mock DM, Stadler DD, Stratton SL, Mock NI: Biotin status assessed longitudinally in pregnant women. J Nutr. 1997 May;127(5):710-6. Pubmed: 9164991
  6. Thuy LP, Sweetman L, Nyhan WL: A new immunochemical assay for biotin. Clin Chim Acta. 1991 Oct 31;202(3):191-7. Pubmed: 1814646
  7. Limat A, Suormala T, Hunziker T, Waelti ER, Braathen LR, Baumgartner R: Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin. Arch Dermatol Res. 1996;288(1):31-8. Pubmed: 8750932
  8. Bigham SL, Ballard JD, Giles KD, Clelland CS, Jeffcoat R, Griffin KS, Farley TD, Bushman DR, Wright JR: Synthesis and possible applications of biotin-linked copper clusters. Physiol Chem Phys Med NMR. 1990;22(2):63-72. Pubmed: 2100006
  9. Mock DM, Stadler DD: Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy. J Am Coll Nutr. 1997 Jun;16(3):252-7. Pubmed: 9176832
  10. Bingham JP, Bian S, Tan ZY, Takacs Z, Moczydlowski E: Synthesis of a biotin derivative of iberiotoxin: binding interactions with streptavidin and the BK Ca2+-activated K+ channel expressed in a human cell line. Bioconjug Chem. 2006 May-Jun;17(3):689-99. Pubmed: 16704206
  11. Mock DM: Biotin status: which are valid indicators and how do we know? J Nutr. 1999 Feb;129(2S Suppl):498S-503S. Pubmed: 10064317
  12. Mock DM, Dyken ME: Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology. 1997 Nov;49(5):1444-7. Pubmed: 9371938
  13. Mock DM, Nyalala JO, Raguseo RM: A direct streptavidin-binding assay does not accurately quantitate biotin in human urine. J Nutr. 2001 Aug;131(8):2208-14. Pubmed: 11481419
  14. Mardach R, Zempleni J, Wolf B, Cannon MJ, Jennings ML, Cress S, Boylan J, Roth S, Cederbaum S, Mock DM: Biotin dependency due to a defect in biotin transport. J Clin Invest. 2002 Jun;109(12):1617-23. Pubmed: 12070309
  15. Mock DM, Heird GM: Urinary biotin analogs increase in humans during chronic supplementation: the analogs are biotin metabolites. Am J Physiol. 1997 Jan;272(1 Pt 1):E83-5. Pubmed: 9038855
  16. Fujimoto W, Inaoki M, Fukui T, Inoue Y, Kuhara T: Biotin deficiency in an infant fed with amino acid formula. J Dermatol. 2005 Apr;32(4):256-61. Pubmed: 15863846
  17. Schenker S, Hu ZQ, Johnson RF, Yang Y, Frosto T, Elliott BD, Henderson GI, Mock DM: Human placental biotin transport: normal characteristics and effect of ethanol. Alcohol Clin Exp Res. 1993 Jun;17(3):566-75. Pubmed: 8333586
  18. Mock NI, Malik MI, Stumbo PJ, Bishop WP, Mock DM: Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency. Am J Clin Nutr. 1997 Apr;65(4):951-8. Pubmed: 9094878
  19. Grafe F, Wohlrab W, Neubert RH, Brandsch M: Transport of biotin in human keratinocytes. J Invest Dermatol. 2003 Mar;120(3):428-33. Pubmed: 12603856
  20. Gravel RA, Narang MA: Molecular genetics of biotin metabolism: old vitamin, new science. J Nutr Biochem. 2005 Jul;16(7):428-31. Pubmed: 15992684
  21. Zempleni J: Uptake, localization, and noncarboxylase roles of biotin. Annu Rev Nutr. 2005;25:175-96. Pubmed: 16011464
  22. Holmberg A, Blomstergren A, Nord O, Lukacs M, Lundeberg J, Uhlen M: The biotin-streptavidin interaction can be reversibly broken using water at elevated temperatures. Electrophoresis. 2005 Feb;26(3):501-10. Pubmed: 15690449

Enzymes

Gene Name:
ACACB
Uniprot ID:
O00763
Gene Name:
ACACA
Uniprot ID:
Q13085
Gene Name:
HLCS
Uniprot ID:
P50747
Reactions
Adenosine triphosphate + Biotin + apo-[methylmalonyl-CoA:pyruvate carboxytransferase] unknown Adenosine monophosphate + Pyrophosphate + [methylmalonyl-CoA:pyruvate carboxytransferase]details
Adenosine triphosphate + Biotin + apo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)] unknown Adenosine monophosphate + Pyrophosphate + [propionyl-CoA:carbon-dioxide ligase (ADP-forming)]details
Adenosine triphosphate + Biotin + apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] unknown Adenosine monophosphate + Pyrophosphate + [3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)]details
Adenosine triphosphate + Biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] unknown Adenosine monophosphate + Pyrophosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)]details
Adenosine triphosphate + Biotin unknown Pyrophosphate + Biotinyl-5'-AMPdetails
Gene Name:
BTD
Uniprot ID:
P43251
Reactions
Biotin amide + Water unknown Biotin + Ammoniadetails
Biocytin + Water unknown Biotin + L-Lysinedetails
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Gene Name:
DKFZp686B20267
Uniprot ID:
Q68D27