2.02012-08-15 08:51:38 -06002015-06-03 17:22:02 -0600ECMDB21665M2MDB002055Meso-2,6-DiaminoheptanedioateMeso-2,6-diaminoheptanedioate is a member of the chemical class known as Alpha Amino Acids and Derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon). This particular compound is at a branch point in lysine biosynthesis where it is either the penultimate step in lysine biosynthesis in E. coli (via diaminopimelate decarboxylase, LysA) or it can be directed towards the synthesis of peptidoglycan (via murE).(2R,6S)-2,6-diaminoheptanedioate(2R,6S)-2,6-diaminoheptanedioic acidMeso-2,6-DiaminoheptanedioateMeso-2,6-Diaminoheptanedioic acidMeso-2,6-DiaminopimelateMeso-2,6-Diaminopimelic acidMeso-DiaminoheptanedioateMeso-Diaminoheptanedioic acidMeso-DPAC7H14N2O4190.1971190.095356946(2R,6S)-2,6-diaminoheptanedioic aciddiaminopimelic acid922-54-3[H][C@](N)(CCC[C@@]([H])(N)C(O)=O)C(O)=OInChI=1S/C7H14N2O4/c8-4(6(10)11)2-1-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5+GMKMEZVLHJARHF-SYDPRGILSA-NCytoplasmlogp-4.13logs-1.13solubility1.41e+01 g/llogp-5.5pka_strongest_acidic1.85pka_strongest_basic9.83iupac(2R,6S)-2,6-diaminoheptanedioic acidaverage_mass190.1971mono_mass190.095356946smiles[H][C@](N)(CCC[C@@]([H])(N)C(O)=O)C(O)=OformulaC7H14N2O4inchiInChI=1S/C7H14N2O4/c8-4(6(10)11)2-1-3-5(9)7(12)13/h4-5H,1-3,8-9H2,(H,10,11)(H,12,13)/t4-,5+inchikeyGMKMEZVLHJARHF-SYDPRGILSA-Npolar_surface_area126.64refractivity43.64polarizability18.68rotatable_bond_count6acceptor_count6donor_count4physiological_charge0formal_charge0Lysine biosynthesisLysine is biosynthesized from L-aspartic acid. L-aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate / orotate:H+ symporter ,
glutamate / aspartate : H+ symporter GltP, dicarboxylate transporter , C4 dicarboxylate / C4 monocarboxylate transporter DauA, glutamate / aspartate ABC transporter
L-aspartic acid is phosphorylated by an ATP-driven Aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-aspartyl-4-phosphate is then dehydrogenated through an NADPH driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP and L-aspartic 4-semialdehyde (involved in methionine biosynthesis).
L-aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water and
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-Succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through a N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid, N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through a N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglyccan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine.
L-lysine is then incorporated into lysine degradation pathway. Lysine also regulate its own biosynthesis by repressing dihydrodipicolinate synthase and also repressing lysine-sensitive aspartokinase 3.
A metabolic connection joins synthesis of an amino acid, lysine, to synthesis of cell wall material. Diaminopimelate is a precursor both for lysine and for cell wall components. The synthesis of lysine, methionine and threonine share two reactions at the start of the three pathways, the reactions converting L-aspartate to L-aspartate semialdehyde. The reaction involving aspartate kinase is carried out by three isozymes, one specific for synthesis of each end product amino acid. Each of the three aspartate kinase isozymes is regulated by its corresponding end product amino acid.PW000771ec00300MetabolicPeptidoglycan biosynthesisec00550Microbial metabolism in diverse environmentsec01120Metabolic pathwayseco01100peptidoglycan biosynthesis IPeptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor.In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space.
The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compund and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl coa undergo acetylation throuhg a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein, follows catalyze the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase realeasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate. This compound undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate through a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, a phosphate and a UDP-N-acetylmuramoyl-L-alanine. This compound interacts with D-glutamic acid and ATP through UDP-N-acetylmuramoylalanine-D-glutamate ligase releasing ADP, A phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter compound then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and ditrans,octacis-undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. ditrans,octacis-undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine.
PW000906Metabolicpeptidoglycan biosynthesis I 2Peptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor.In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space. The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compund and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl coa undergo acetylation throuhg a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein, follows catalyze the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase realeasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate. This compound undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate through a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, a phosphate and a UDP-N-acetylmuramoyl-L-alanine. This compound interacts with D-glutamic acid and ATP through UDP-N-acetylmuramoylalanine-D-glutamate ligase releasing ADP, A phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter compound then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelyl-D-alanyl-D-alanine-diphosphoundecaprenol which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. Undecaprenyl-diphospho-N-acetylmuramoyl-(N-acetylglucosamine)-L-alanyl-D-glutaminyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine.PW002062MetabolicSpecdb::CMs1086372Specdb::NmrOneD256448Specdb::NmrOneD256449Specdb::NmrOneD256450Specdb::NmrOneD256451Specdb::NmrOneD256452Specdb::NmrOneD256453Specdb::NmrOneD256454Specdb::NmrOneD256455Specdb::NmrOneD256456Specdb::NmrOneD256457Specdb::NmrOneD256458Specdb::NmrOneD256459Specdb::NmrOneD256460Specdb::NmrOneD256461Specdb::NmrOneD256462Specdb::NmrOneD256463Specdb::NmrOneD256464Specdb::NmrOneD256465Specdb::NmrOneD256466Specdb::NmrOneD256467Specdb::MsMs28184Specdb::MsMs28185Specdb::MsMs28186Specdb::MsMs34742Specdb::MsMs34743Specdb::MsMs3474499290842C0068030308APIDiaminopimelate decarboxylaseP00861DCDA_ECOLIlysAhttp://ecmdb.ca/proteins/P00861.xmlDiaminopimelate epimeraseP0A6K1DAPF_ECOLIdapFhttp://ecmdb.ca/proteins/P0A6K1.xmlUDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligaseP22188MURE_ECOLImurEhttp://ecmdb.ca/proteins/P22188.xmlDiaminopimelate epimeraseP0A6K1DAPF_ECOLIdapFhttp://ecmdb.ca/proteins/P0A6K1.xmlMeso-2,6-Diaminoheptanedioate <> L-Lysine + Carbon dioxideR00451Diaminopimelic acid <> Meso-2,6-DiaminoheptanedioateR02735Adenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamate + Meso-2,6-Diaminoheptanedioate <> ADP + Phosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminoheptanedioateR02788Diaminopimelic acid > Meso-2,6-DiaminoheptanedioateMeso-2,6-Diaminoheptanedioate > L-Lysine + Carbon dioxideAdenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamate + Meso-2,6-Diaminoheptanedioate > ADP + Inorganic phosphate + UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate-D-alanineMeso-2,6-Diaminoheptanedioate + Hydrogen ion > L-Lysine + Carbon dioxide + L-LysinePW_R002533UDP-N-acetylmuramoyl-L-alanyl-D-glutamate + Meso-2,6-Diaminoheptanedioate + Adenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamate > Adenosine diphosphate + Phosphate + Hydrogen ion + UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate + ADPPW_R003450Adenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamate + Meso-2,6-Diaminoheptanedioate <> ADP + Phosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminoheptanedioateMeso-2,6-Diaminoheptanedioate <> L-Lysine + Carbon dioxideAdenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamate + Meso-2,6-Diaminoheptanedioate <> ADP + Phosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminoheptanedioate