2.02012-05-31 13:03:39 -06002015-06-03 15:53:40 -0600ECMDB01024M2MDB000229Phosphohydroxypyruvic acidPhosphohydroxypyruvic acid is a prduct of both enzyme phosphoglycerate dehydrogenase [EC 1.1.1.95] and phosphoserine transaminase [EC 2.6.1.52] in glycine, serine and threonine metabolism pathway (KEGG).2-Oxo-3-(phosphonooxy)-Propanoate2-Oxo-3-(phosphonooxy)-Propanoic acid3-p-Hydroxy-pyr3-P-Hydroxypyruvate3-P-Hydroxypyruvic acid3-p-OH-pyr3-p-OH-pyruvate3-p-OH-pyruvic acid3-Phosphohydroxy-pyr3-Phosphohydroxypyruvate3-Phosphohydroxypyruvic acid3-Phosphonooxypyruvate3-Phosphonooxypyruvic acid3PHPAPhosphohydroxypyruatePhosphohydroxypyruic acidPhosphohydroxypyruvatePhosphohydroxypyruvic acidC3H5O7P184.0414183.9772890262-oxo-3-(phosphonooxy)propanoic acidphosphohydroxypyruvate3913-50-6OC(=O)C(=O)COP(O)(O)=OInChI=1S/C3H5O7P/c4-2(3(5)6)1-10-11(7,8)9/h1H2,(H,5,6)(H2,7,8,9)LFLUCDOSQPJJBE-UHFFFAOYSA-NSolidCytosollogp-1.75logs-1.14solubility1.34e+01 g/llogp-0.87pka_strongest_acidic1.02iupac2-oxo-3-(phosphonooxy)propanoic acidaverage_mass184.0414mono_mass183.977289026smilesOC(=O)C(=O)COP(O)(O)=OformulaC3H5O7PinchiInChI=1S/C3H5O7P/c4-2(3(5)6)1-10-11(7,8)9/h1H2,(H,5,6)(H2,7,8,9)inchikeyLFLUCDOSQPJJBE-UHFFFAOYSA-Npolar_surface_area121.13refractivity30.56polarizability12.69rotatable_bond_count4acceptor_count6donor_count3physiological_charge-3formal_charge0Glycine, serine and threonine metabolismec00260Methane metabolismec00680Vitamin B6 metabolismec00750Microbial metabolism in diverse environmentsec01120Metabolic pathwayseco01100Secondary Metabolites: cysteine biosynthesis from serineThe pathway starts with a 3-phosphoglyceric acid interacting with an NAD driven D-3-phosphoglycerate dehydrogenase / α-ketoglutarate reductase resulting in an NADH, a hydrogen ion and a phosphohydroxypyruvic acid. This compound then interacts with an L-glutamic acid through a 3-phosphoserine aminotransferase / phosphohydroxythreonine aminotransferase resulting in a oxoglutaric acid and a DL-D-phosphoserine. The latter compound then interacts with a water molecule through a phosphoserine phosphatase resulting in a phosphate and an L-serine. The L-serine interacts with an acetyl-coa through a serine acetyltransferase resulting in a release of a Coenzyme A and a O-Acetylserine. The O-acetylserine then interacts with a hydrogen sulfide through a O-acetylserine sulfhydrylase A resulting in an acetic acid, a hydrogen ion and an L-cysteinePW000977Metaboliccysteine biosynthesisThe pathway of cysteine biosynthesis is a two-step conversion starting from L-serine and yielding L-cysteine. L-serine biosynthesis is shown for context.
L-cysteine can also be synthesized from sulfate derivatives.
The process through L-serine involves a serine acetyltransferase that produces a O-acetylserine which reacts together with hydrogen sulfide through a cysteine synthase complex in order to produce L-cysteine and acetic acid.
Hydrogen sulfide is produced from a sulfate. Sulfate reacts with sulfate adenylyltransferase to produce adenosine phosphosulfate. This compound in turn is phosphorylated through a adenylyl-sulfate kinase into a phosphoadenosine phosphosulfate which in turn reacts with a phosphoadenosine phosphosulfate reductase to produce a sulfite. The sulfite reacts with a sulfite reductase to produce the hydrogen sulfide.
This pathway is regulated at the genetic level in its second step, wtih both cysteine synthase isozymes being under the positive control of the cysteine-responsive transcription factor CysB. It is also subject to very strong feedback inhibition of its first step by the final pathway product, cysteine.
Although two cysteine synthase isozymes exist, only cysteine synthase A (CysK) forms a complex with serine acetyltransferase. CysK is also the only one of the two cysteine synthases that is required for cell viability on cysteine-free medium.
Both steps in this pathway are reversible. Based on genetic and proteomic data, it appears that the cysteine synthases may actually act as a sulfur scavenging system during sulfur starvation, stripping sulfur off of L-cysteine, generating any number of variant amino acids in the process.PW000800Metabolicserine biosynthesis and metabolismSerine biosynthesis is a major metabolic pathway in E. coli. Its end product, serine, is not only used in protein synthesis, but also as a precursor for the biosynthesis of glycine, cysteine, tryptophan, and phospholipids. In addition, it directly or indirectly serves as a source of one-carbon units for the biosynthesis of various compounds.
The biosynthesis of serine starts with 3-phosphoglyceric acid being metabolized by a NAD driven D-3-phosphoglycerate dehydrogenase / α-ketoglutarate reductase resulting in the release of a NADH, a hydrogen ion and a phosphohydroxypyruvic acid. The latter compound then interacts with an L-glutamic acid through a 3-phosphoserine aminotransferase / phosphohydroxythreonine aminotransferase resulting in oxoglutaric acid and DL-D-phosphoserine.
The DL-D-phosphoserine can also be imported into the cytoplasm through a phosphonate ABC transporter. The DL-D-phosphoserine is dephosphorylated by interacting with a water molecule through a phosphoserine phosphatase resulting in the release of a phosphate and an L-serine
L-serine is then metabolized by being dehydrated through either a L-serine dehydratase 2 or a L-serine dehydratase 1 resulting in the release of a water molecule, a hydrogen ion and a 2-aminoacrylic acid. The latter compound is an isomer of a 2-iminopropanoate which reacts spontaneously with a water molecule and a hydrogen ion resulting in the release of Ammonium and pyruvic acid. Pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an acetyl-CoA.
PW000809Metabolichomoserine biosynthesisSERSYN-PWYSpecdb::CMs2973Specdb::CMs37896Specdb::CMs160784Specdb::NmrOneD146110Specdb::NmrOneD146111Specdb::NmrOneD146112Specdb::NmrOneD146113Specdb::NmrOneD146114Specdb::NmrOneD146115Specdb::NmrOneD146116Specdb::NmrOneD146117Specdb::NmrOneD146118Specdb::NmrOneD146119Specdb::NmrOneD146120Specdb::NmrOneD146121Specdb::NmrOneD146122Specdb::NmrOneD146123Specdb::NmrOneD146124Specdb::NmrOneD146125Specdb::NmrOneD146126Specdb::NmrOneD146127Specdb::NmrOneD146128Specdb::NmrOneD146129Specdb::MsMs23018Specdb::MsMs23019Specdb::MsMs23020Specdb::MsMs29816Specdb::MsMs29817Specdb::MsMs29818Specdb::MsMs2276754Specdb::MsMs2276755Specdb::MsMs2276756Specdb::MsMs3092701Specdb::MsMs3092702Specdb::MsMs3092703HMDB01024105103C03232309333-P-HYDROXYPYRUVATEHPVPhosphohydroxypyruvic acidKeseler, 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." Anal Chem 80:2939-2948.18331064Thiele I, Swainston N, Fleming RM, Hoppe A, Sahoo S, Aurich MK, Haraldsdottir H, Mo ML, Rolfsson O, Stobbe MD, Thorleifsson SG, Agren R, Bolling C, Bordel S, Chavali AK, Dobson P, Dunn WB, Endler L, Hala D, Hucka M, Hull D, Jameson D, Jamshidi N, Jonsson JJ, Juty N, Keating S, Nookaew I, Le Novere N, Malys N, Mazein A, Papin JA, Price ND, Selkov E Sr, Sigurdsson MI, Simeonidis E, Sonnenschein N, Smallbone K, Sorokin A, van Beek JH, Weichart D, Goryanin I, Nielsen J, Westerhoff HV, Kell DB, Mendes P, Palsson BO: A community-driven global reconstruction of human metabolism. Nat Biotechnol. 2013 Mar 3. doi: 10.1038/nbt.2488.23455439Zhao G, Winkler ME: A novel alpha-ketoglutarate reductase activity of the serA-encoded 3-phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric aciduria. J Bacteriol. 1996 Jan;178(1):232-9.8550422Achouri Y, Rider MH, Schaftingen EV, Robbi M: Cloning, sequencing and expression of rat liver 3-phosphoglycerate dehydrogenase. Biochem J. 1997 Apr 15;323 ( Pt 2):365-70.9163325D-3-phosphoglycerate dehydrogenaseP0A9T0SERA_ECOLIserAhttp://ecmdb.ca/proteins/P0A9T0.xmlPhosphoserine aminotransferaseP23721SERC_ECOLIserChttp://ecmdb.ca/proteins/P23721.xmlUncharacterized Nudix hydrolase nudLP43337NUDL_ECOLInudLhttp://ecmdb.ca/proteins/P43337.xmlPhosphohydroxypyruvic acid + L-Glutamate > alpha-Ketoglutarate + PhosphoserineR041733-Phosphoglycerate + NAD > Phosphohydroxypyruvic acid + Hydrogen ion + NADHPGLYCDEHYDROG-RXN3-Phospho-D-glycerate + NAD <> Phosphohydroxypyruvic acid + NADH + Hydrogen ionR01513Phosphoserine + alpha-Ketoglutarate <> Phosphohydroxypyruvic acid + L-GlutamateR04173Phosphohydroxypyruvic acid + Water > Hydroxypyruvic acid + PhosphateRXN0-65623-Phosphoglycerate + NAD <> Hydrogen ion + Phosphohydroxypyruvic acid + NADHPGLYCDEHYDROG-RXNPhosphoserine + Oxoglutaric acid <> Phosphohydroxypyruvic acid + L-GlutamatePSERTRANSAM-RXN3-Phospho-D-glycerate + NAD > Phosphohydroxypyruvic acid + NADHR01513Phosphoserine + Oxoglutaric acid > Phosphohydroxypyruvic acid + L-GlutamatePSERTRANSAM-RXNPhosphoserine + alpha-Ketoglutarate + O-Phospho-4-hydroxy-L-threonine <> Phosphohydroxypyruvic acid + L-Glutamate + 2-Oxo-3-hydroxy-4-phosphobutanoic acidR04173 3-Phospho-D-glycerate + NAD + D-2-Hydroxyglutaric acid <> Phosphohydroxypyruvic acid + NADH + Hydrogen ion + alpha-KetoglutarateR01513 3-Phosphoglyceric acid + NAD + 3-Phosphoglycerate > NADH + Hydrogen ion + Phosphohydroxypyruvic acidPW_R002843Phosphohydroxypyruvic acid + L-Glutamic acid + L-Glutamate > Oxoglutaric acid + DL-O-PhosphoserinePW_R0028443 3-Phospho-D-glycerate + NAD <> Phosphohydroxypyruvic acid + NADH + Hydrogen ionPhosphohydroxypyruvic acid + L-Glutamate > alpha-Ketoglutarate + Phosphoserine