Human Metabolome Database Version 3.5

Showing metabocard for Biotin (HMDB00030)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-05-29 13:24:30 -0600
HMDB ID HMDB00030
Secondary Accession Numbers None
Metabolite Identification
Common Name Biotin
Description Biotin 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 Link_out, 16011464 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C10H16N2O3S
Average Molecular Weight 244.311
Monoisotopic Molecular Weight 244.088163078
IUPAC Name 5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl]pentanoic acid
Traditional IUPAC Name biotin
CAS Registry Number 58-85-5
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 Key YBJHBAHKTGYVGT-ZKWXMUAHSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aliphatic Heteropolycyclic Compounds
Class Thienoimidazolidines
Sub Class Biotin and Derivatives
Other Descriptors
  • Aliphatic Heteropolycyclic Compounds
  • Heterocyclic Fatty Acids
  • Thia Fatty Acids
Substituents
  • Carboxylic Acid
  • Imidazolidine
  • Imidazolidinone
  • Thioether
  • Thiolane
  • Urea
Direct Parent Biotin and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Food
Biofunction
  • Component of Biotin metabolism
  • Essential vitamins
Application
  • .
Cellular locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Nucleus
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 232 °C Not Available
Boiling Point Not Available Not Available
Water Solubility 0.22 mg/mL at 25 °C Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 1.22 g/L ALOGPS
LogP 0.17 ALOGPS
LogP 0.32 ChemAxon
LogS -2.30 ALOGPS
pKa (strongest acidic) 4.4 ChemAxon
pKa (strongest basic) -1.9 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 3 ChemAxon
Polar Surface Area 78.43 A2 ChemAxon
Rotatable Bond Count 5 ChemAxon
Refractivity 60.05 ChemAxon
Polarizability 24.92 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies)
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies )
MS/MS Spectrum GC-MS
[1H,13C] 2D NMR Spectrum
[1H,1H] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
  • Nucleus
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • All Tissues
  • Prostate
Pathways
Name SMPDB Link KEGG Link
Biotin Metabolism SMP00066 map00780 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.0034 (0.002 - 0.0051) uM Newborn (0-30 days old) Both Normal
  • Geigy Scient...
Blood Detected and Quantified
0.0016 (0.0009 - 0.0028) uM Children (1-13 year old) Not Specified Normal
  • Geigy Scient...
Blood Detected and Quantified
0.0024 (0.0008 - 0.0041) uM Adult (>18 years old) Female Normal
  • Geigy Scient...
Blood Detected and Quantified
0.00127 +/- 0.00067 uM Adult (>18 years old) Both Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
0.000557 +/- 0.000307 uM Adult (>18 years old) Not Specified Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
0.0005 +/- 0.0002 uM Adult (>18 years old) Not Specified Normal
Urine Detected and Quantified
0.014 (0.002-0.044) umol/mmol creatinine Children (1-13 year old) Both Normal
  • Geigy Scient...
Urine Detected and Quantified
0.049 +/- 0.035 umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected and Quantified
0.023 (0.013-0.032) umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Cerebrospinal Fluid (CSF) Detected and Quantified 0.08198 (0.00033-0.421) uM Not Specified Not Specified acute lymphoblastic leukemia
Cerebrospinal Fluid (CSF) Detected and Quantified 0.16 uM Not Specified Not Specified Bronchopulmonary dysplasia
Cerebrospinal Fluid (CSF) Detected and Quantified 0.00039 uM Not Specified Not Specified Burkitt's lymphoma
Cerebrospinal Fluid (CSF) Detected and Quantified 0.000447 +/- 0.000217 uM Not Specified Not Specified Dementia
Cerebrospinal Fluid (CSF) Detected and Quantified 0.000336 +/- 8.603e-05 uM Not Specified Not Specified Epilepsy
Cerebrospinal Fluid (CSF) Detected and Quantified 0.0229 uM Not Specified Not Specified Head injury
Cerebrospinal Fluid (CSF) Detected and Quantified 0.0273 (0.0247-0.0299) uM Not Specified Not Specified Lymphoblastic lymphoma
Cerebrospinal Fluid (CSF) Detected and Quantified 0.000459 +/- 9.0000e-05 uM Not Specified Not Specified Motor Neuron disease
Cerebrospinal Fluid (CSF) Detected and Quantified 0.000324 +/- 0.000107 uM Not Specified Not Specified Multiple sclerosis
Cerebrospinal Fluid (CSF) Detected and Quantified 0.000692 +/- 0.000602 uM Not Specified Not Specified Polyneuropathy
Cerebrospinal Fluid (CSF) Detected and Quantified 0.000438 +/- 0.000156 uM Not Specified Not Specified Vascular encephalopathies
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID DB00121 Link_out
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB014510
KNApSAcK ID C00000756 Link_out
Chemspider ID 149962 Link_out
KEGG Compound ID C00120 Link_out
BioCyc ID BIOTIN Link_out
BiGG ID 33931 Link_out
Wikipedia Link Biotin Link_out
NuGOwiki Link HMDB00030 Link_out
Metagene Link HMDB00030 Link_out
METLIN ID 243 Link_out
PubChem Compound 171548 Link_out
PDB ID BTN Link_out
ChEBI ID 15956 Link_out
References
Synthesis Reference Corey, E. J.; Mehrotra, Mukund M. A simple and enantioselective synthesis of (+)-biotin. Tetrahedron Letters (1988), 29(1), 57-60.
Material Safety Data Sheet (MSDS) Download (PDF)
General References
  1. Thuy LP, Belmont J, Nyhan WL: Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. Prenat Diagn. 1999 Feb;19(2):108-12. Pubmed: 10215065 Link_out
  2. 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 Link_out
  3. 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 Link_out
  4. 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 Link_out
  5. Thuy LP, Sweetman L, Nyhan WL: A new immunochemical assay for biotin. Clin Chim Acta. 1991 Oct 31;202(3):191-7. Pubmed: 1814646 Link_out
  6. 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 Link_out
  7. 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 Link_out
  8. 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 Link_out
  9. 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 Link_out
  10. Mock DM: Biotin status: which are valid indicators and how do we know? J Nutr. 1999 Feb;129(2S Suppl):498S-503S. Pubmed: 10064317 Link_out
  11. 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 Link_out
  12. 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 Link_out
  13. 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 Link_out
  14. 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 Link_out
  15. 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 Link_out
  16. 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 Link_out
  17. 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 Link_out
  18. 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 Link_out
  19. 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 Link_out
  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 Link_out
  21. Zempleni J: Uptake, localization, and noncarboxylase roles of biotin. Annu Rev Nutr. 2005;25:175-96. Pubmed: 16011464 Link_out
  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 Link_out

Enzymes
Name: Acetyl-CoA carboxylase 2
Reactions: Not Available
Gene Name: ACACB
Uniprot ID: O00763 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Pyruvate carboxylase, mitochondrial
Reactions: Not Available
Gene Name: PC
Uniprot ID: P11498 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Acetyl-CoA carboxylase 1
Reactions: Not Available
Gene Name: ACACA
Uniprot ID: Q13085 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Propionyl-CoA carboxylase beta chain, mitochondrial
Reactions: Not Available
Gene Name: PCCB
Uniprot ID: P05166 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Propionyl-CoA carboxylase alpha chain, mitochondrial
Reactions: Not Available
Gene Name: PCCA
Uniprot ID: P05165 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
Reactions: Not Available
Gene Name: MCCC2
Uniprot ID: Q9HCC0 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Biotin--protein ligase
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'-AMP details
Gene Name: HLCS
Uniprot ID: P50747 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial
Reactions: Not Available
Gene Name: MCCC1
Uniprot ID: Q96RQ3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Biotinidase
Reactions:
Biotin amide + Water unknown Biotin + Ammonia details
Biocytin + Water unknown Biotin + L-Lysine details
Gene Name: BTD
Uniprot ID: P43251 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 1B1
Reactions: Not Available
Gene Name: CYP1B1
Uniprot ID: Q16678 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Sodium-dependent multivitamin transporter
Reactions: Not Available
Gene Name: SLC5A6
Uniprot ID: Q9Y289 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Putative uncharacterized protein DKFZp686B20267
Reactions: Not Available
Gene Name: DKFZp686B20267
Uniprot ID: Q68D27 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA