2.0 2012-05-31 14:07:32 -0600 2015-06-03 15:54:50 -0600 ECMDB04220 M2MDB000655 Biotinyl-5'-AMP 5'-biotinyl-AMP (B-AMP) is the active form of biotin. Biotin is essential to maintain metabolic homeostasis and as regulator of gene expression. The vitamin biotin plays an essential role in gluconeogenesis, fatty acid synthesis, and carbohydrate metabolism because of its role as cofactor of five carboxylases; pyruvate carboxylase (PC), propionyl-CoA carboxylase (PCC), methylcrotonyl-CoA carboxylase, and two forms of acetyl-CoA carboxylase (ACC-1 and ACC-2). Carboxylase biotinylation is catalyzed by the enzyme holocarboxylase synthetase (HCS) through a reaction that involves the transformation of biotin into B-AMP and its subsequent attachment to a specific lysine residue in the carboxylases. B-AMP is also required to activate a signal transduction cascade that includes a soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG). The regulatory role of biotin in the biotin cycle seems to be limited to the expression of proteins involved in the transport and utilization of exogenous vitamin while having no effect on biotinidase mRNA levels, enzyme responsible for biotin recycling during carboxylase turnover. (+)-Biotinyl 5'-adenylate (+)-Biotinyl 5'-adenylic acid 5'-Adenylate anhydride with biotin 5'-Adenylate monoanhydride with biotin 5'-Adenylic acid anhydride with biotin 5'-Adenylic acid monoanhydride with biotin B-AMP Beta-AMP Bio-5-AMP Biotin anhydride with 5'-adenylate Biotin anhydride with 5'-adenylic acid Biotinoyl 5'-adenylate Biotinoyl 5'-adenylic acid Biotinyl 5'-AMP Biotinyl-AMP [3aS-(3aa,4b,6aa)]-5'-Adenylate monoanhydride with hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-pentanoate [3aS-(3aa,4b,6aa)]-5'-Adenylate monoanhydride with hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-pentanoic acid [3aS-(3aa,4b,6aa)]-5'-Adenylic acid monoanhydride with hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-pentanoate [3aS-(3aa,4b,6aa)]-5'-Adenylic acid monoanhydride with hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-pentanoic acid β-AMP C20H28N7O9PS 573.517 573.140682731 {[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}({5-[(4S)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl]pentanoyl}oxy)phosphinic acid [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy({5-[(4S)-2-oxo-hexahydrothieno[3,4-d]imidazolidin-4-yl]pentanoyl}oxy)phosphinic acid 4130-20-5 NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OC(=O)CCCC[C@@H]2SCC3NC(=O)NC23)[C@@H](O)[C@H]1O InChI=1S/C20H28N7O9PS/c21-17-14-18(23-7-22-17)27(8-24-14)19-16(30)15(29)10(35-19)5-34-37(32,33)36-12(28)4-2-1-3-11-13-9(6-38-11)25-20(31)26-13/h7-11,13,15-16,19,29-30H,1-6H2,(H,32,33)(H2,21,22,23)(H2,25,26,31)/t9?,10-,11+,13?,15-,16-,19-/m1/s1 UTQCSTJVMLODHM-CFYKWCKVSA-N Solid Cytoplasm Periplasm logp -1.24 ALOGPS logs -2.41 ALOGPS solubility 2.24e+00 g/l ALOGPS logp -4.1 ChemAxon pka_strongest_acidic 0.83 ChemAxon pka_strongest_basic 4.99 ChemAxon iupac {[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}({5-[(4S)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl]pentanoyl}oxy)phosphinic acid ChemAxon average_mass 573.517 ChemAxon mono_mass 573.140682731 ChemAxon smiles NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OC(=O)CCCC[C@@H]2SCC3NC(=O)NC23)[C@@H](O)[C@H]1O ChemAxon formula C20H28N7O9PS ChemAxon inchi InChI=1S/C20H28N7O9PS/c21-17-14-18(23-7-22-17)27(8-24-14)19-16(30)15(29)10(35-19)5-34-37(32,33)36-12(28)4-2-1-3-11-13-9(6-38-11)25-20(31)26-13/h7-11,13,15-16,19,29-30H,1-6H2,(H,32,33)(H2,21,22,23)(H2,25,26,31)/t9?,10-,11+,13?,15-,16-,19-/m1/s1 ChemAxon inchikey UTQCSTJVMLODHM-CFYKWCKVSA-N ChemAxon polar_surface_area 233.27 ChemAxon refractivity 130.63 ChemAxon polarizability 53.92 ChemAxon rotatable_bond_count 11 ChemAxon acceptor_count 11 ChemAxon donor_count 6 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 Specdb::CMs 26041 Specdb::CMs 38732 Specdb::CMs 282399 Specdb::CMs 371015 Specdb::CMs 371016 Specdb::CMs 371017 Specdb::CMs 371018 Specdb::CMs 371019 Specdb::CMs 371020 Specdb::CMs 371021 Specdb::CMs 371022 Specdb::CMs 371023 Specdb::CMs 371024 Specdb::CMs 371025 Specdb::CMs 371026 Specdb::CMs 371027 Specdb::CMs 371028 Specdb::CMs 371029 Specdb::CMs 371030 Specdb::CMs 371031 Specdb::CMs 371032 Specdb::CMs 371033 Specdb::CMs 371034 Specdb::CMs 371035 Specdb::CMs 371036 Specdb::NmrOneD 47902 Specdb::NmrOneD 47903 Specdb::NmrOneD 47904 Specdb::NmrOneD 47905 Specdb::NmrOneD 47906 Specdb::NmrOneD 47907 Specdb::NmrOneD 47908 Specdb::NmrOneD 47909 Specdb::NmrOneD 47910 Specdb::NmrOneD 47911 Specdb::NmrOneD 47912 Specdb::NmrOneD 47913 Specdb::NmrOneD 47914 Specdb::NmrOneD 47915 Specdb::NmrOneD 47916 Specdb::NmrOneD 47917 Specdb::NmrOneD 47918 Specdb::NmrOneD 47919 Specdb::NmrOneD 47920 Specdb::NmrOneD 47921 Specdb::MsMs 27284 Specdb::MsMs 27285 Specdb::MsMs 27286 Specdb::MsMs 33842 Specdb::MsMs 33843 Specdb::MsMs 33844 Specdb::MsMs 2709473 Specdb::MsMs 2709474 Specdb::MsMs 2709475 Specdb::MsMs 2995838 Specdb::MsMs 2995839 Specdb::MsMs 2995840 HMDB04220 440839 389681 C05921 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 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 Pacheco-Alvarez D, Solorzano-Vargas RS, Gonzalez-Noriega A, Michalak C, Zempleni J, Leon-Del-Rio A: Biotin availability regulates expression of the sodium-dependent multivitamin transporter and the rate of biotin uptake in HepG2 cells. Mol Genet Metab. 2005 Aug;85(4):301-7. 15905112 Solorzano-Vargas RS, Pacheco-Alvarez D, Leon-Del-Rio A: Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5325-30. 11959985 Christner, James E.; Coon, Minor J. Synthesis of (+)-biotinyl 5'-adenylate. Methods Enzymol. (1970), 18(Pt. A), 386-90. Bifunctional protein BirA P06709 BIRA_ECOLI birA http://ecmdb.ca/proteins/P06709.xml Adenosine triphosphate + Biotin <> Pyrophosphate + Biotinyl-5'-AMP R01074 Biotinyl-5'-AMP + Apo-[carboxylase] <> Adenosine monophosphate + Holo-[carboxylase] R05145 Adenosine triphosphate + Biotin > Biotinyl-5'-AMP + Pyrophosphate PW_R002491 Biotinyl-5'-AMP > Biotin-Carboxyl Carrying Protein PW_R002493 Biotin + Adenosine triphosphate > diphosphate + Biotinyl-5'-AMP + Pyrophosphate PW_R002501 Biotinyl-5'-AMP + apo-[carboxylase] > Adenosine monophosphate + Biotin-Carboxyl Carrying Protein PW_R002502 Adenosine triphosphate + Biotin <> Pyrophosphate + Biotinyl-5'-AMP