2.0 2012-05-31 09:55:34 -0600 2015-09-13 12:56:05 -0600 ECMDB00030 M2MDB000008 Biotin 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. 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 acts as a carboxyl carrier in carboxylation reactions. 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. The biotin moiety is covalently bound to the epsilon amino group of a Lys residue in carboxylases in a domain 60-80 amino acids long. The domain is structurally similar among carboxylases from bacteria to mammals. Posttranscriptional events related to ribosomal activity and protein folding may further contribute to effects of biotin on gene expression. (+)-Biotin (+)-cis-Hexahydro-2-oxo-1H-thieno[3,4]imidazole-4-valerate (+)-cis-Hexahydro-2-oxo-1H-thieno[3,4]imidazole-4-valeric acid (3aS,4S,6aR)-Hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-valerate (3aS,4S,6aR)-Hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-valeric acid -(+)-biotin 1swk 1swn 1swr 5-(2-Oxohexahydro-1H-thieno[3,4-D]imidazol-4-yl)pentanoate 5-(2-Oxohexahydro-1H-thieno[3,4-D]imidazol-4-yl)pentanoic acid <I>d</I>-biotin Biodermatin Bioepiderm Bios Bios h Bios II Biotin Cis-(+)-Tetrahydro-2-oxothieno[3,4]imidazoline-4-valerate Cis-(+)-Tetrahydro-2-oxothieno[3,4]imidazoline-4-valeric acid Cis-Hexahydro-2-oxo-1H-thieno(3,4)imidazole-4-valerate Cis-Hexahydro-2-oxo-1H-thieno(3,4)imidazole-4-valeric acid Cis-Tetrahydro-2-oxothieno(3,4-D)imidazoline-4-valerate Cis-Tetrahydro-2-oxothieno(3,4-D)imidazoline-4-valeric acid Coenzyme R D(+)-Biotin D-(+)-Biotin D-Biotin D-Biotin factor S Delta-(+)-Biotin Delta-Biotin Delta-Biotin factor S Factor S Factor S (vitamin) Hexahydro-2-oxo-1H-thieno(3,4-D)imidazole-4-pentanoate Hexahydro-2-oxo-1H-thieno(3,4-D)imidazole-4-pentanoic acid hexahydro-2-oxo-[3As-(3a,4b,6a)]-1H-thieno[3,4-D]imidazole-4-pentanoate hexahydro-2-oxo-[3As-(3a,4b,6a)]-1H-thieno[3,4-D]imidazole-4-pentanoic acid Hexahydro-2-oxo-[3aS-(3aa,4b,6aa)]-1H-Thieno[3,4-D]imidazole-4-pentanoate Hexahydro-2-oxo-[3aS-(3aa,4b,6aa)]-1H-Thieno[3,4-D]imidazole-4-pentanoic acid Hexahydro-2-oxo-[3as-(3alpha,4beta,6alpha)]-1H-Thieno[3,4-D]imidazole-4-pentanoate Hexahydro-2-oxo-[3as-(3alpha,4beta,6alpha)]-1H-Thieno[3,4-D]imidazole-4-pentanoic acid hexahydro-2-oxo-[3As-(3α,4β,6α)]-1H-thieno[3,4-D]imidazole-4-pentanoate hexahydro-2-oxo-[3As-(3α,4β,6α)]-1H-thieno[3,4-D]imidazole-4-pentanoic acid Lutavit H2 Meribin Rovimix H 2 Vitamin B7 Vitamin H Vitamin-h δ-(+)-Biotin δ-Biotin δ-Biotin factor S C10H16N2O3S 244.311 244.088163078 5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid 5-[(3aS,4S,6aR)-2-oxo-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoic acid 58-85-5 [H][C@]12CS[C@@H](CCCCC(O)=O)[C@@]1([H])NC(=O)N2 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 YBJHBAHKTGYVGT-ZKWXMUAHSA-N Solid Cytosol Extra-organism Periplasm logp 0.17 ALOGPS logs -2.30 ALOGPS solubility 1.22e+00 g/l ALOGPS melting_point 232 oC logp 0.32 ChemAxon pka_strongest_acidic 4.4 ChemAxon pka_strongest_basic -1.9 ChemAxon iupac 5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid ChemAxon average_mass 244.311 ChemAxon mono_mass 244.088163078 ChemAxon smiles [H][C@]12CS[C@@H](CCCCC(O)=O)[C@@]1([H])NC(=O)N2 ChemAxon formula C10H16N2O3S ChemAxon inchi 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 ChemAxon inchikey YBJHBAHKTGYVGT-ZKWXMUAHSA-N ChemAxon polar_surface_area 78.43 ChemAxon refractivity 60.05 ChemAxon polarizability 24.92 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 3 ChemAxon donor_count 3 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Biotin metabolism Biotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase.In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in a S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. This compound is then dehydrated through ad (3R)-hydroxymyristoyl-[acp] dehydratase producing a enoylglutaryl-[acp] methyl ester. This compound is then reduced through a NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester. This compound interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester. This compound is then reduced through a NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce a enoylpimeloyl-[acp] methyl ester. This compound is then reduced by a NADPH dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester. This compound then reacts with water through a carboxylesterase resulting in a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through a 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8 diaminonanoate transaminase resulting in a S-adenosyl-4-methylthio-2-oxobutanoate and 7,8 diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion and a S-adenosylmethionine through a biotin synthase to produce Biotin and releasing l-methionine and a 5-deoxyadenosine. Biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and Biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting ina biotin caroxyl carrying protein.This product then enters the fatty acid biosynthesis. PW000762 ec00780 Metabolic Metabolic pathways eco01100 biotin-carboxyl carrier protein assembly The assembly of a biotin-carboxyl carrier protein starts with a biotin carboxyl carrier protein monomer interacting with an ATP, and a biotin through a biotin -acetyl-coa-carboxylase ligase resulting in the release of a hydrogen ion, an AMP, a diphosphate and a biotynylated BCCP monomer. The latter compound reacts spontaneously to create a biotinylated BCCP dimer. This compound in turn reacts with a hydrogen carbonate and an ATP driven biotin carboxylase resulting in the release of ADP, a hydrogen Ion , a phosphate and a carboxylated biotinylated BCCP dimer. This complex can be degraded by reacting with water, an acetyl0CoA, and an ATP driven acetyl-CoA carboxyltransferase resulting in the release of a hydrogen ion, a phosphate, an ADP, a malonyl-CoA and a biotynylated BCCP dimer PW002067 Metabolic biotin biosynthesis from 7-keto-8-aminopelargonate PWY0-1507 biotin-carboxyl carrier protein assembly PWY0-1264 Specdb::CMs 857 Specdb::CMs 1994 Specdb::CMs 3215 Specdb::CMs 30490 Specdb::CMs 30963 Specdb::CMs 37254 Specdb::CMs 130453 Specdb::CMs 138187 Specdb::CMs 1047151 Specdb::CMs 1047153 Specdb::CMs 1047155 Specdb::CMs 1047157 Specdb::CMs 1047158 Specdb::EiMs 1972 Specdb::NmrOneD 1039 Specdb::NmrOneD 4827 Specdb::NmrOneD 4828 Specdb::NmrOneD 294995 Specdb::NmrOneD 294996 Specdb::NmrOneD 294997 Specdb::NmrOneD 294998 Specdb::NmrOneD 294999 Specdb::NmrOneD 295000 Specdb::NmrOneD 295001 Specdb::NmrOneD 295002 Specdb::NmrOneD 295003 Specdb::NmrOneD 295004 Specdb::NmrOneD 295005 Specdb::NmrOneD 295006 Specdb::NmrOneD 295007 Specdb::NmrOneD 295008 Specdb::NmrOneD 295009 Specdb::NmrOneD 295010 Specdb::NmrOneD 295011 Specdb::NmrOneD 295012 Specdb::NmrOneD 295013 Specdb::NmrOneD 295014 Specdb::MsMs 6162 Specdb::MsMs 6163 Specdb::MsMs 6164 Specdb::MsMs 6165 Specdb::MsMs 6166 Specdb::MsMs 6167 Specdb::MsMs 6168 Specdb::MsMs 6169 Specdb::MsMs 6170 Specdb::MsMs 179691 Specdb::MsMs 179692 Specdb::MsMs 179693 Specdb::MsMs 182025 Specdb::MsMs 182026 Specdb::MsMs 182027 Specdb::MsMs 374645 Specdb::MsMs 436925 Specdb::MsMs 436926 Specdb::MsMs 437350 Specdb::MsMs 437351 Specdb::MsMs 437352 Specdb::MsMs 437353 Specdb::MsMs 437354 Specdb::MsMs 438622 Specdb::MsMs 439629 Specdb::NmrTwoD 932 Specdb::NmrTwoD 936 HMDB00030 171548 149962 C00120 15956 BIOTIN BTN Biotin Keseler, 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. 21097882 Kanehisa, 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. 22080510 van 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. 17765195 Winder, 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. 18331064 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. 19212411 Thuy LP, Belmont J, Nyhan WL: Prenatal diagnosis and treatment of holocarboxylase synthetase deficiency. Prenat Diagn. 1999 Feb;19(2):108-12. 10215065 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. 9022537 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. 9416479 Mock DM, Stadler DD, Stratton SL, Mock NI: Biotin status assessed longitudinally in pregnant women. J Nutr. 1997 May;127(5):710-6. 9164991 Thuy LP, Sweetman L, Nyhan WL: A new immunochemical assay for biotin. Clin Chim Acta. 1991 Oct 31;202(3):191-7. 1814646 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. 8750932 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. 2100006 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. 9176832 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. 16704206 Mock DM: Biotin status: which are valid indicators and how do we know? J Nutr. 1999 Feb;129(2S Suppl):498S-503S. 10064317 Mock DM, Dyken ME: Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology. 1997 Nov;49(5):1444-7. 9371938 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. 11481419 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. 12070309 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. 9038855 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. 15863846 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. 8333586 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. 9094878 Grafe F, Wohlrab W, Neubert RH, Brandsch M: Transport of biotin in human keratinocytes. J Invest Dermatol. 2003 Mar;120(3):428-33. 12603856 Gravel RA, Narang MA: Molecular genetics of biotin metabolism: old vitamin, new science. J Nutr Biochem. 2005 Jul;16(7):428-31. 15992684 Zempleni J: Uptake, localization, and noncarboxylase roles of biotin. Annu Rev Nutr. 2005;25:175-96. 16011464 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. 15690449 Corey, E. J.; Mehrotra, Mukund M. A simple and enantioselective synthesis of (+)-biotin. Tetrahedron Letters (1988), 29(1), 57-60. http://hmdb.ca/system/metabolites/msds/000/000/020/original/HMDB00030.pdf?1358893586 Bifunctional protein BirA P06709 BIRA_ECOLI birA http://ecmdb.ca/proteins/P06709.xml Biotin synthase P12996 BIOB_ECOLI bioB http://ecmdb.ca/proteins/P12996.xml Biotin sulfoxide reductase P20099 BISC_ECOLI bisC http://ecmdb.ca/proteins/P20099.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml [2Fe-2S] iron-sulfur cluster + S-Adenosylmethionine + Dethiobiotin > [2Fe-1S] desulfurated iron-sulfur cluster + Biotin + 5'-Deoxyadenosine + Hydrogen ion + L-Methionine D-Biotin D-sulfoxide + Hydrogen ion + NADH > Biotin + Water + NAD D-Biotin D-sulfoxide + Hydrogen ion + NADPH > Biotin + Water + NADP Adenosine triphosphate + Biotin <> Pyrophosphate + Biotinyl-5'-AMP R01074 Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine R01078 <i>S</i>-sulfanyl-[acceptor] + Dethiobiotin + S-Adenosylmethionine > an unsulfurated sulfur acceptor + Biotin + 5'-Deoxyadenosine + L-Methionine + Hydrogen ion 2.8.1.6-RXN Benzo[a]pyrene-4,5-oxide + Red-Thioredoxin Biotin + Water + Ox-Thioredoxin RXN0-6277 Dethiobiotin + Hydrogen sulfide + 2 S-adenosyl-L-methionine > Biotin +2 L-Methionine +2 5'-Deoxyadenosine Adenosine triphosphate + Biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] > Adenosine monophosphate + Pyrophosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)] Adenosine triphosphate + Biotin + Apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] <> Adenosine monophosphate + Pyrophosphate + [Acetyl-CoA:carbon-dioxide ligase (ADP-forming)] R04562 Adenosine triphosphate + Biotin > Biotinyl-5'-AMP + Pyrophosphate PW_R002491 Biocytin + Water > Biotin + L-Lysine + L-Lysine PW_R002492 Dethiobiotin + 2 S-adenosyl-L-methionine + 2 Hydrogen ion + a sulfurated [sulfur carrier] > Biotin +2 L-Methionine +2 5'-Deoxyadenosine PW_R002499 Biotin Sulfoxide > Biotin PW_R002500 Biotin + Adenosine triphosphate > diphosphate + Biotinyl-5'-AMP + Pyrophosphate PW_R002501 Adenosine triphosphate + Biotin + Biotin-Carboxyl Carrying Protein > Hydrogen ion + Adenosine monophosphate + Pyrophosphate + Biotinylated [BCCP monomer] PW_R006041 Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine Adenosine triphosphate + Biotin <> Pyrophosphate + Biotinyl-5'-AMP Dethiobiotin + Sulfur donor + 2 S-Adenosylmethionine + 2 e- + 2 Hydrogen ion <> Biotin +2 L-Methionine +2 5'-Deoxyadenosine