2.02012-05-31 13:49:42 -06002015-09-13 12:56:10 -0600ECMDB01311M2MDB000334D-Lactic acidD-Lactic acid is the end product of the enzyme Glyoxalase ([EC:3.1.2.6] hydroxyacyl-glutathione hydrolase) which converts the intermediate substrate S-lactoyl-glutathione to reduced glutathione and D-lactate. (OMIM 138790)(-)-Lactate(-)-Lactic acid(<i>R</i>)-2-hydroxypropanate(R)-(-)-Lactate(R)-(-)-Lactic acid(R)-2-hydroxypropanate(R)-2-hydroxypropanic acid(R)-2-Hydroxypropanoate(R)-2-Hydroxypropanoic acid(R)-2-Hydroxypropionate(R)-2-Hydroxypropionic acid(R)-a-Hydroxypropionate(R)-a-Hydroxypropionic acid(R)-alpha-Hydroxypropionate(R)-alpha-Hydroxypropionic acid(R)-Lactate(R)-Lactic acid(R)-α-Hydroxypropionate(R)-α-Hydroxypropionic acidD-(-)-LactateD-(-)-Lactic acidD-2-HydroxypropanoateD-2-Hydroxypropanoic acidD-2-HydroxypropionateD-2-Hydroxypropionic acidD-LactateD-Lactic acidDelta-(-)-LactateDelta-(-)-Lactic acidDelta-2-HydroxypropanoateDelta-2-Hydroxypropanoic acidDelta-2-HydroxypropionateDelta-2-Hydroxypropionic acidDelta-LactateDelta-Lactic acidDLAL-(+)-LactateL-(+)-Lactic acidL-LactateL-Lactic acidPropelTisulacδ-(-)-Lactateδ-(-)-Lactic acidδ-2-Hydroxypropanoateδ-2-Hydroxypropanoic acidδ-2-Hydroxypropionateδ-2-Hydroxypropionic acidδ-Lactateδ-Lactic acidC3H6O390.077990.031694058(2S)-2-hydroxypropanoic acid(α)-lactate10326-41-7C[C@@H](O)C(O)=OInChI=1S/C3H6O3/c1-2(4)3(5)6/h2,4H,1H3,(H,5,6)/t2-/m1/s1JVTAAEKCZFNVCJ-UWTATZPHSA-NSolidCytosolExtra-organismPeriplasmmelting_point52.8 Clogp-0.47pka_strongest_acidic3.78pka_strongest_basic-3.7iupac(2S)-2-hydroxypropanoic acidaverage_mass90.0779mono_mass90.031694058smilesC[C@@H](O)C(O)=OformulaC3H6O3inchiInChI=1S/C3H6O3/c1-2(4)3(5)6/h2,4H,1H3,(H,5,6)/t2-/m1/s1inchikeyJVTAAEKCZFNVCJ-UWTATZPHSA-Npolar_surface_area57.53refractivity18.84polarizability8.06rotatable_bond_count1acceptor_count3donor_count2physiological_charge-1formal_charge0Amino sugar and nucleotide sugar metabolismec00520Pyruvate metabolismec00620Microbial metabolism in diverse environmentsec01120Amino sugar and nucleotide sugar metabolism IThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound can either be isomerized or deaminated into Beta-D-fructofuranose 6-phosphate through a glucosamine-fructose-6-phosphate aminotransferase and a glucosamine-6-phosphate deaminase respectively.
Glucosamine 6-phosphate undergoes a reversible reaction to glucosamine 1 phosphate through a phosphoglucosamine mutase. This compound is then acetylated through a bifunctional protein glmU to produce a N-Acetyl glucosamine 1-phosphate.
N-Acetyl glucosamine 1-phosphate enters the nucleotide sugar synthesis by reacting with UTP and hydrogen ion through a bifunctional protein glmU releasing pyrophosphate and a Uridine diphosphate-N-acetylglucosamine.This compound can either be isomerized into a UDP-N-acetyl-D-mannosamine or undergo a reaction with phosphoenolpyruvic acid through UDP-N-acetylglucosamine 1-carboxyvinyltransferase releasing a phosphate and a UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate.
UDP-N-acetyl-D-mannosamine undergoes a NAD dependent dehydrogenation through a UDP-N-acetyl-D-mannosamine dehydrogenase, releasing NADH, a hydrogen ion and a UDP-N-Acetyl-alpha-D-mannosaminuronate, This compound is then used in the production of enterobacterial common antigens.
UDP-N-Acetyl-alpha-D-glucosamine-enolpyruvate is reduced through a NADPH dependent UDP-N-acetylenolpyruvoylglucosamine reductase, releasing a NADP and a UDP-N-acetyl-alpha-D-muramate. This compound is involved in the D-glutamine and D-glutamate metabolism.
PW000886MetabolicAmino sugar and nucleotide sugar metabolism IIThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase.
The beta-D-fructofuranose 6 -phosphate is isomerized in a reversible reaction into an alpha-D-mannose 6-phosphate. This compound can also be introduced into the cell from the periplasmic space through a mannose PTS permease that phosphorylates an alpha-D-mannose. Alpha-D-mannose 6-phosphate undergoes a reversible reaction through a phosphomannomutase to produce an alpha-D-mannose 1-phosphate.
The alpha-D-mannose 1-phosphate enters the nucleotide sugar metabolism through a reaction with GTP producing a GDP-mannose and releasing a pyrophosphate, all through a mannose-1-phosphate guanylyltransferase. GDP-mannose is then dehydrated to produce GDP-4-dehydro-6-deoxy-alpha-D-mannose through a GDP-mannose 4,6-dehydratase. This compound is then used to synthesize GDP-Beta-L-fucose through a NADPH dependent GDP-L-fucose synthase.
Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively.PW000887MetabolicAmino sugar and nucleotide sugar metabolism IIIThe synthesis of amino sugars and nucleotide sugars starts with the phosphorylation of N-Acetylmuramic acid (MurNac) through its transport from the periplasmic space to the cytoplasm. Once in the cytoplasm, MurNac and water undergo a reversible reaction through a N-acetylmuramic acid 6-phosphate etherase, producing a D-lactic acid and N-Acetyl-D-Glucosamine 6-phosphate. This latter compound can also be introduced into the cytoplasm through a phosphorylating PTS permase in the inner membrane that allows for the transport of N-Acetyl-D-glucosamine from the periplasmic space. N-Acetyl-D-Glucosamine 6-phosphate can also be obtained from chitin dependent reactions. Chitin is hydrated through a bifunctional chitinase to produce chitobiose. This in turn gets hydrated by a beta-hexosaminidase to produce N-acetyl-D-glucosamine. The latter undergoes an atp dependent phosphorylation leading to the production of N-Acetyl-D-Glucosamine 6-phosphate.
N-Acetyl-D-Glucosamine 6-phosphate is then be deacetylated in order to produce Glucosamine 6-phosphate through a N-acetylglucosamine-6-phosphate deacetylase. This compound is then deaminased into Beta-D-fructofuranose 6-phosphate through a glucosamine-6-phosphate deaminase.
Beta-D-fructofuranose 6-phosphate is isomerized into a beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase. The compound is then isomerized by a putative beta-phosphoglucomutase to produce a beta-D-glucose 1-phosphate. This compound enters the nucleotide sugar metabolism through uridylation resulting in a UDP-glucose. UDP-glucose is then dehydrated through a UDP-glucose 6-dehydrogenase to produce a UDP-glucuronic acid. This compound undergoes a NAD dependent reaction through a bifunctional polymyxin resistance protein to produce UDP-Beta-L-threo-pentapyranos-4-ulose. This compound then reacts with L-glutamic acid through a UDP-4-amino-4-deoxy-L-arabinose--oxoglutarate aminotransferase to produce an oxoglutaric acid and UDP-4-amino-4-deoxy-beta-L-arabinopyranose
The latter compound interacts with a N10-formyl-tetrahydrofolate through a bifunctional polymyxin resistance protein ArnA, resulting in a tetrahydrofolate, a hydrogen ion and a UDP-4-deoxy-4-formamido-beta-L-arabinopyranose, which in turn reacts with a product of the methylerythritol phosphate and polysoprenoid biosynthesis pathway, di-trans,octa-cis-undecaprenyl phosphate to produce a 4-deoxy-4-formamido-alpha-L-arabinopyranosyl ditrans, octacis-undecaprenyl phosphate.
Alpha-D-glucose is introduced into the cytoplasm through a glucose PTS permease, which phosphorylates the compound in order to produce an alpha-D-glucose 6-phosphate. This compound is then modified through a phosphoglucomutase 1 to yield alpha-D-glucose 1-phosphate. This compound can either be adenylated to produce ADP-glucose or uridylylated to produce galactose 1-phosphate through glucose-1-phosphate adenyllyltransferase and galactose-1-phosphate uridylyltransferase respectively.PW000895Metabolic1,6-anhydro-<i>N</i>-acetylmuramic acid recyclingAnhydromuropeptides (mainly GlcNAc-1,6-anhMurNAc-L-Ala-γ-D-Glu-DAP-D-Ala) are steadily released during growth by lytic transglycosylases and endopeptidases and imported back into the cytoplasm for recycling. During bacterial growth, a very large proportion of the peptidoglycan polymer is degraded and reused in a process termed cell wall recycling. For example, the Gram-negative bacterium Escherichia coli recovers about half of its cell wall within one generation.
The anhydromuropeptides are imported by the ampG-encoded muropeptide:H+ symporter. Once inside the cytoplasm, the anhydromuropeptides are hydrolyzed by N-acetylmuramoyl-L-alanine amidase (ampD), β-N-acetylhexosaminidase (nagZ) and L,D-carboxypeptidase A (ldcA), yielding N-acetyl-β-D-glucosamine, 1,6-anhydro-N-acetyl-β-muramate, L-alanyl-γ-D-glutamyl-meso-diaminopimelate and D-alanine.
1,6-anhydro-N-acetyl-β-muramate is phosphorylated by anhydro-N-acetylmuramic acid kinase (anmK) and then converted into N-acetyl-D-glucosamine 6-phosphate by N-acetylmuramic acid 6-phosphate etherase (murQ). This is a branch point, as this compound could be directed either for further degradation or for recycling into new peptidoglycan monomers, as described in this pathway. The final product of this pathway, UDP-N-acetyl-α-D-muramate, is one of the precursors for peptidoglycan biosynthesis.
The tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, which is generated by muramoyltetrapeptide carboxypeptidase, can be degraded further, as described in muropeptide degradation. However, the vast majority is recycled by muropeptide ligase (mpl). This enzyme is a dedicated recycling enzyme that attaches the recovered Ala-Glu-DAP tripeptide to UDP-N-acetyl-α-D-muramate, thereby substituting three amino acid ligases of the peptidoglycan de novobiosynthetic pathway.
Although exogenously provided 1,6-anhydro-N-acetyl-β-muramate can be taken up by Escherichia coli, it can not serve as the sole source of carbon for growth, suggesting that it may be toxic to the cell. (EcoCyc)
PW002064Metabolicmethylglyoxal degradation IIThe most common pathway for methylglyoxal detoxification is the glyoxalase system, which is composed of two enzymes that together convert methylglyoxal to (R)-lactate in the presence of glutathione. However, in E. coli, a single enzyme, glyoxalase III, catalyzes this conversion in a single step without involvement of glutathione. Activity of glyoxalase III increases at the transition to stationary phase and expression is dependent on RpoS, suggesting that this pathway may be important during stationary phase. (EcoCyc)PW002084Metabolicmixed acid fermentationFERMENTATION-PWYmethylglyoxal degradation IPWY-5386methylglyoxal degradation IIPWY-9011,6-anhydro-<i>N</i>-acetylmuramic acid recyclingPWY0-1261Specdb::CMs434Specdb::CMs2365Specdb::CMs30161Specdb::CMs30601Specdb::CMs37346Specdb::CMs152925Specdb::CMs1053840Specdb::CMs1053841Specdb::CMs1053843Specdb::CMs1053845Specdb::CMs1053847Specdb::EiMs1087Specdb::NmrOneD1162Specdb::NmrOneD1197Specdb::NmrOneD4808Specdb::NmrOneD6072Specdb::NmrOneD6073Specdb::NmrOneD6074Specdb::NmrOneD6075Specdb::NmrOneD6076Specdb::NmrOneD6077Specdb::NmrOneD6078Specdb::NmrOneD6079Specdb::NmrOneD6080Specdb::NmrOneD6081Specdb::NmrOneD6082Specdb::NmrOneD6083Specdb::NmrOneD6084Specdb::NmrOneD6085Specdb::NmrOneD6086Specdb::NmrOneD6087Specdb::NmrOneD6088Specdb::NmrOneD6089Specdb::NmrOneD6090Specdb::NmrOneD6091Specdb::NmrOneD166457Specdb::MsMs301Specdb::MsMs302Specdb::MsMs303Specdb::MsMs3467Specdb::MsMs3468Specdb::MsMs3469Specdb::MsMs3470Specdb::MsMs3471Specdb::MsMs178011Specdb::MsMs178012Specdb::MsMs178013Specdb::MsMs180324Specdb::MsMs180325Specdb::MsMs180326Specdb::MsMs438026Specdb::MsMs438027Specdb::MsMs438028Specdb::MsMs438029Specdb::MsMs438030Specdb::MsMs1474450Specdb::MsMs2258028Specdb::MsMs2258582Specdb::MsMs2260001Specdb::MsMs3055172Specdb::MsMs3055173Specdb::NmrTwoD989Specdb::NmrTwoD1195HMDB013116150355423C00256341D-LACTATELACDLAKeseler, 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-D590.21097882Kanehisa, 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." 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U.S. (1997), 5 pp. http://hmdb.ca/system/metabolites/msds/000/001/173/original/HMDB01311.pdf?1358461953D-lactate dehydrogenaseP06149DLD_ECOLIdldhttp://ecmdb.ca/proteins/P06149.xmlHydroxyacylglutathione hydrolaseP0AC84GLO2_ECOLIgloBhttp://ecmdb.ca/proteins/P0AC84.xmlD-lactate dehydrogenase_P52643LDHD_ECOLIldhAhttp://ecmdb.ca/proteins/P52643.xmlN-acetylmuramic acid 6-phosphate etheraseP76535MURQ_ECOLImurQhttp://ecmdb.ca/proteins/P76535.xmlMolecular chaperone Hsp31 and glyoxalase 3P31658hchAhttp://ecmdb.ca/proteins/P31658.xmlL-lactate permeaseP33231LLDP_ECOLIlldPhttp://ecmdb.ca/proteins/P33231.xmlGlycolate permease glcAQ46839GLCA_ECOLIglcAhttp://ecmdb.ca/proteins/Q46839.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlD-Lactic acid + NAD <> Hydrogen ion + NADH + Pyruvic acidR00704DLACTDEHYDROGNAD-RXNWater + S-Lactoylglutathione > Glutathione + Hydrogen ion + D-Lactic acidR01736GLYOXII-RXND-Lactic acid + Ubiquinone-8 > Pyruvic acid + Ubiquinol-8N-Acetylmuramic acid 6-phosphate + Water <> N-Acetyl-D-Glucosamine 6-Phosphate + D-Lactic acidR08555RXN0-4641S-Lactoylglutathione + Water <> Glutathione + D-Lactic acidR01736GLYOXII-RXNan electron-transfer-related quinone + D-Lactic acid > an electron-transfer-related quinol + Pyruvic acidDLACTDEHYDROGFAD-RXNNAD + D-Lactic acid < Hydrogen ion + NADH + Pyruvic acidDLACTDEHYDROGNAD-RXND-Lactic acid + Hydrogen ion < Pyruvaldehyde + WaterGLYOXIII-RXND-Lactic acid + NAD > Pyruvic acid + NADHD-Lactic acid > Pyruvaldehyde + WaterGLYOXIII-RXNN-Acetylmuramic acid 6-phosphate + Water > N-Acetyl-D-Glucosamine 6-Phosphate + D-Lactic acidD-Lactic acid <> Pyruvaldehyde + WaterR09796 MurNAc-6-P + Water > D-Lactic acid + N-Acetylglucosamine 6-phosphatePW_R003303Pyruvaldehyde + Water > D-Lactic acid + Hydrogen ionPW_R006086N-Acetylmuramate 6-phosphate + Water <> N-Acetyl-D-Glucosamine 6-Phosphate + D-Lactic acidPW_R006028D-Lactic acid + 2 Hydrogen ion + an ubiquinol > Pyruvic acid + ubiquinonePW_R006087D-Lactic acid + NAD <> Hydrogen ion + NADH + Pyruvic acidD-Lactic acid <> Pyruvaldehyde + WaterD-Lactic acid + NAD <> Hydrogen ion + NADH + Pyruvic acidD-Lactic acid <> Pyruvaldehyde + Water