2.02012-05-31 14:07:32 -06002015-06-03 15:54:50 -0600ECMDB04220M2MDB000655Biotinyl-5'-AMP5'-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 acid5'-Adenylate anhydride with biotin5'-Adenylate monoanhydride with biotin5'-Adenylic acid anhydride with biotin5'-Adenylic acid monoanhydride with biotinB-AMPBeta-AMPBio-5-AMPBiotin anhydride with 5'-adenylateBiotin anhydride with 5'-adenylic acidBiotinoyl 5'-adenylateBiotinoyl 5'-adenylic acidBiotinyl 5'-AMPBiotinyl-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 acidβ-AMPC20H28N7O9PS573.517573.140682731{[(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 acid4130-20-5NC1=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]1OInChI=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/s1UTQCSTJVMLODHM-CFYKWCKVSA-NSolidCytoplasmPeriplasmlogp-1.24logs-2.41solubility2.24e+00 g/llogp-4.1pka_strongest_acidic0.83pka_strongest_basic4.99iupac{[(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 acidaverage_mass573.517mono_mass573.140682731smilesNC1=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]1OformulaC20H28N7O9PSinchiInChI=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/s1inchikeyUTQCSTJVMLODHM-CFYKWCKVSA-Npolar_surface_area233.27refractivity130.63polarizability53.92rotatable_bond_count11acceptor_count11donor_count6physiological_charge-1formal_charge0Biotin metabolismBiotin (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.
PW000762ec00780MetabolicSpecdb::CMs26041Specdb::CMs38732Specdb::CMs282399Specdb::CMs371015Specdb::CMs371016Specdb::CMs371017Specdb::CMs371018Specdb::CMs371019Specdb::CMs371020Specdb::CMs371021Specdb::CMs371022Specdb::CMs371023Specdb::CMs371024Specdb::CMs371025Specdb::CMs371026Specdb::CMs371027Specdb::CMs371028Specdb::CMs371029Specdb::CMs371030Specdb::CMs371031Specdb::CMs371032Specdb::CMs371033Specdb::CMs371034Specdb::CMs371035Specdb::CMs371036Specdb::NmrOneD47902Specdb::NmrOneD47903Specdb::NmrOneD47904Specdb::NmrOneD47905Specdb::NmrOneD47906Specdb::NmrOneD47907Specdb::NmrOneD47908Specdb::NmrOneD47909Specdb::NmrOneD47910Specdb::NmrOneD47911Specdb::NmrOneD47912Specdb::NmrOneD47913Specdb::NmrOneD47914Specdb::NmrOneD47915Specdb::NmrOneD47916Specdb::NmrOneD47917Specdb::NmrOneD47918Specdb::NmrOneD47919Specdb::NmrOneD47920Specdb::NmrOneD47921Specdb::MsMs27284Specdb::MsMs27285Specdb::MsMs27286Specdb::MsMs33842Specdb::MsMs33843Specdb::MsMs33844Specdb::MsMs2709473Specdb::MsMs2709474Specdb::MsMs2709475Specdb::MsMs2995838Specdb::MsMs2995839Specdb::MsMs2995840HMDB04220440839389681C05921Kanehisa, 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-D114.22080510Winder, 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 80:2939-2948.18331064Pacheco-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):301-7.15905112Solorzano-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):5325-30.11959985Christner, James E.; Coon, Minor J. Synthesis of (+)-biotinyl 5'-adenylate. Methods Enzymol. (1970), 18(Pt. A), 386-90. Bifunctional protein BirAP06709BIRA_ECOLIbirAhttp://ecmdb.ca/proteins/P06709.xmlAdenosine triphosphate + Biotin <> Pyrophosphate + Biotinyl-5'-AMPR01074Biotinyl-5'-AMP + Apo-[carboxylase] <> Adenosine monophosphate + Holo-[carboxylase]R05145Adenosine triphosphate + Biotin > Biotinyl-5'-AMP + PyrophosphatePW_R002491Biotinyl-5'-AMP > Biotin-Carboxyl Carrying ProteinPW_R002493Biotin + Adenosine triphosphate > diphosphate + Biotinyl-5'-AMP + PyrophosphatePW_R002501Biotinyl-5'-AMP + apo-[carboxylase] > Adenosine monophosphate + Biotin-Carboxyl Carrying ProteinPW_R002502Adenosine triphosphate + Biotin <> Pyrophosphate + Biotinyl-5'-AMP