2.0 2012-05-31 10:22:16 -0600 2015-09-13 12:56:06 -0600 ECMDB00159 M2MDB000061 L-Phenylalanine Phenylalanine is an essential amino acid and the precursor for the amino acid tyrosine. Phenylalanine is a precursor of the neurotransmitters called catecholamines, which are adrenalin-like substances. Normal metabolism of phenylalanine requires biopterin, iron, niacin, vitamin B6, copper and vitamin C. Phenylalanine and tyrosine, like L-dopa, produce a catecholamine effect. (-)-b-Phenylalanine (-)-beta-Phenylalanine (-)-β-Phenylalanine (L)-Phenylalanine (S)-(-)-Phenylalanine (S)-2-amino-3-phenylpropanoate (S)-2-amino-3-phenylpropanoic acid (S)-2-Amino-3-phenylpropionate (S)-2-Amino-3-phenylpropionic acid (S)-a-amino-b-Phenylpropionate (S)-a-amino-b-Phenylpropionic acid (S)-a-amino-Benzenepropanoate (S)-a-amino-Benzenepropanoic acid (S)-a-Aminobenzenepropanoate (S)-a-Aminobenzenepropanoic acid (S)-a-Aminohydrocinnamate (S)-a-Aminohydrocinnamic acid (S)-alpha-Amino-benzenepropanoate (S)-alpha-Amino-benzenepropanoic acid (S)-alpha-Amino-beta-phenylpropionate (S)-alpha-Amino-beta-phenylpropionic acid (S)-alpha-Aminobenzenepropanoate (S)-alpha-Aminobenzenepropanoic acid (S)-alpha-Aminohydrocinnamate (S)-alpha-Aminohydrocinnamic acid (S)-Phenylalanine (S)-α-amino-Benzenepropanoate (S)-α-amino-Benzenepropanoic acid (S)-α-amino-β-Phenylpropionate (S)-α-amino-β-Phenylpropionic acid (S)-α-Aminobenzenepropanoate (S)-α-Aminobenzenepropanoic acid (S)-α-Aminohydrocinnamate (S)-α-Aminohydrocinnamic acid 3-Phenyl-L-alanine a-Aminohydrocinnamate a-Aminohydrocinnamic acid Alpha-Aminohydrocinnamate Alpha-Aminohydrocinnamic acid b-Phenyl-a-alanine b-Phenyl-L-alanine b-Phenylalanine Beta-Phenyl-alpha-alanine Beta-Phenyl-L-alanine Beta-Phenylalanine Endophenyl F L-2-Amino-3-phenylpropionate L-2-Amino-3-phenylpropionic acid Phe Phenyl-Alanine Phenylalamine Phenylalanine α-Aminohydrocinnamate α-Aminohydrocinnamic acid β-Phenyl-L-alanine β-Phenyl-α-alanine β-Phenylalanine C9H11NO2 165.1891 165.078978601 (2S)-2-amino-3-phenylpropanoic acid L-phenylalanine 63-91-2 N[C@@H](CC1=CC=CC=C1)C(O)=O InChI=1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m0/s1 COLNVLDHVKWLRT-QMMMGPOBSA-N Solid Cytosol Extra-organism Periplasm logp -1.35 ALOGPS logs -1.60 ALOGPS solubility 4.14e+00 g/l ALOGPS melting_point 283 oC logp -1.2 ChemAxon pka_strongest_acidic 2.47 ChemAxon pka_strongest_basic 9.45 ChemAxon iupac (2S)-2-amino-3-phenylpropanoic acid ChemAxon average_mass 165.1891 ChemAxon mono_mass 165.078978601 ChemAxon smiles N[C@@H](CC1=CC=CC=C1)C(O)=O ChemAxon formula C9H11NO2 ChemAxon inchi InChI=1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m0/s1 ChemAxon inchikey COLNVLDHVKWLRT-QMMMGPOBSA-N ChemAxon polar_surface_area 63.32 ChemAxon refractivity 45.12 ChemAxon polarizability 17.03 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 3 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Phenylalanine metabolism The pathways of the metabolism of phenylalaline begins with the conversion of chorismate to prephenate through a P-protein (chorismate mutase:pheA). Prephenate then interacts with a hydrogen ion through the same previous enzyme resulting in a release of carbon dioxide, water and a phenolpyruvic acid. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine. Phenolpyruvic acid can also be obtained from a reversivle reaction with ammonia, a reduced acceptor and a D-amino acid dehydrogenase, resulting in a water, an acceptor and a D-phenylalanine, which can be then transported into the periplasmic space by aromatic amino acid exporter. L-phenylalanine also interacts in two reversible reactions, one involved with oxygen through a catalase peroxidase resulting in a carbon dioxide and 2-phenylacetamide. The other reaction involved an interaction with oxygen through a phenylalanine aminotransferase resulting in a oxoglutaric acid and phenylpyruvic acid. L-phenylalanine can be imported into the cytoplasm through an aromatic amino acid:H+ symporter AroP. The compound can also be imported into the periplasmic space through a transporter: L-amino acid efflux transporter. PW000921 ec00360 Metabolic Phenylalanine, tyrosine and tryptophan biosynthesis ec00400 Aminoacyl-tRNA biosynthesis ec00970 ABC transporters ec02010 inner membrane transport list of inner membrane transport complexes, transporting compounds from the periplasmic space to the cytosol This pathway should be updated regularly with the new inner membrae transports added PW000786 Metabolic phenylalanine biosynthesis The pathways of biosynthesis of phenylalaline and tyrosine are intimately connected. First step of both pathways is the conversion of chorismate to prephenate, the third step of both is the conversion of a ketoacid to the aminoacid through transamination. The two pathways differ only in the second step of their three-step reaction sequences: In the case of phenylalanine biosynthesis, a dehydratase converts prephenate to phenylpyruvate(reaction occurs slowly in the absence of enzymic activity); in the case of tyrosine biosynthesis, a dehydrogenase converts prephenate to p-hydroxyphenylpyruvate. Also in both pathways the first two steps are catalyzed by two distinc active sites on a single protein. Thus the first step of each pathway can be catalyzed by two enzyme: those associated with both the phenylalanine specific dehydratase and the tyrosine specific dehydrogenase. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine PW000807 Metabolic tRNA Charging 2 This pathway groups together all E. coli tRNA charging reactions. PW000803 Metabolic tRNA charging This pathway groups together all E. coli tRNA charging reactions. PW000799 Metabolic tRNA charging TRNA-CHARGING-PWY phenylalanine biosynthesis I PHESYN Specdb::CMs 389 Specdb::CMs 390 Specdb::CMs 391 Specdb::CMs 1252 Specdb::CMs 1304 Specdb::CMs 2830 Specdb::CMs 30069 Specdb::CMs 30210 Specdb::CMs 30607 Specdb::CMs 30732 Specdb::CMs 30771 Specdb::CMs 31032 Specdb::CMs 31033 Specdb::CMs 37329 Specdb::CMs 138002 Specdb::CMs 145736 Specdb::CMs 1051754 Specdb::CMs 1051755 Specdb::CMs 1051757 Specdb::EiMs 1975 Specdb::NmrOneD 1118 Specdb::NmrOneD 1177 Specdb::NmrOneD 142590 Specdb::NmrOneD 142591 Specdb::NmrOneD 142592 Specdb::NmrOneD 142593 Specdb::NmrOneD 142594 Specdb::NmrOneD 142595 Specdb::NmrOneD 142596 Specdb::NmrOneD 142597 Specdb::NmrOneD 142598 Specdb::NmrOneD 142599 Specdb::NmrOneD 142600 Specdb::NmrOneD 142601 Specdb::NmrOneD 142602 Specdb::NmrOneD 142603 Specdb::NmrOneD 142604 Specdb::NmrOneD 142605 Specdb::NmrOneD 142606 Specdb::NmrOneD 142607 Specdb::NmrOneD 142608 Specdb::NmrOneD 142609 Specdb::NmrOneD 166451 Specdb::MsMs 248 Specdb::MsMs 249 Specdb::MsMs 250 Specdb::MsMs 3191 Specdb::MsMs 3192 Specdb::MsMs 3193 Specdb::MsMs 3194 Specdb::MsMs 3195 Specdb::MsMs 3196 Specdb::MsMs 3197 Specdb::MsMs 3198 Specdb::MsMs 3199 Specdb::MsMs 3200 Specdb::MsMs 3201 Specdb::MsMs 3202 Specdb::MsMs 3203 Specdb::MsMs 3204 Specdb::MsMs 3205 Specdb::MsMs 3206 Specdb::MsMs 3207 Specdb::MsMs 3208 Specdb::MsMs 3209 Specdb::MsMs 3210 Specdb::MsMs 3211 Specdb::MsMs 3212 Specdb::NmrTwoD 975 Specdb::NmrTwoD 1177 HMDB00159 6140 5910 C00079 17295 PHE PHE_LFZW L-Phenylalanine Keseler, I. 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Huaxue Fanying Gongcheng Yu Gongyi (2006), 22(2), 146-150. http://hmdb.ca/system/metabolites/msds/000/000/110/original/HMDB00159.pdf?1358894687 Aspartate aminotransferase P00509 AAT_ECOLI aspC http://ecmdb.ca/proteins/P00509.xml Aromatic-amino-acid aminotransferase P04693 TYRB_ECOLI tyrB http://ecmdb.ca/proteins/P04693.xml Histidinol-phosphate aminotransferase P06986 HIS8_ECOLI hisC http://ecmdb.ca/proteins/P06986.xml Phenylalanyl-tRNA synthetase beta chain P07395 SYFB_ECOLI pheT http://ecmdb.ca/proteins/P07395.xml Phenylalanyl-tRNA synthetase alpha chain P08312 SYFA_ECOLI pheS http://ecmdb.ca/proteins/P08312.xml P-protein P0A9J8 PHEA_ECOLI pheA http://ecmdb.ca/proteins/P0A9J8.xml Catalase-peroxidase P13029 KATG_ECOLI katG http://ecmdb.ca/proteins/P13029.xml Branched-chain-amino-acid aminotransferase P0AB80 ILVE_ECOLI ilvE http://ecmdb.ca/proteins/P0AB80.xml Uncharacterized amino-acid ABC transporter ATP-binding protein yecC P37774 YECC_ECOLI yecC http://ecmdb.ca/proteins/P37774.xml Inner membrane amino-acid ABC transporter permease protein yecS P0AFT2 YECS_ECOLI yecS http://ecmdb.ca/proteins/P0AFT2.xml Aromatic amino acid transport protein AroP P15993 AROP_ECOLI aroP http://ecmdb.ca/proteins/P15993.xml Phenylalanine-specific permease P24207 PHEP_ECOLI pheP http://ecmdb.ca/proteins/P24207.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Inner membrane protein yddG P46136 YDDG_ECOLI yddG http://ecmdb.ca/proteins/P46136.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) + tRNA(Phe) <> Adenosine monophosphate + L-Phenylalanyl-tRNA(Phe) + Pyrophosphate + L-Phenylalanyl-tRNA(Phe) R03660 alpha-Ketoglutarate + L-Phenylalanine <> L-Glutamate + Phenylpyruvic acid R00694 L-Arogenate <> L-Phenylalanine + Water + Carbon dioxide R00691 L-Phenylalanine + Oxygen <> 2-Phenylacetamide + Carbon dioxide R00698 Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) <> Adenosine monophosphate + Pyrophosphate + L-Phenylalanyl-tRNA(Phe) R03660 Phenylpyruvic acid + L-Glutamate <> L-Phenylalanine + Oxoglutaric acid PHEAMINOTRANS-RXN Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) > Adenosine monophosphate + Pyrophosphate + L-phenylalanyl-tRNA(Phe) L-Phenylalanine + Adenosine triphosphate + Hydrogen ion + tRNA(Phe) + L-Phenylalanine > Adenosine monophosphate + Pyrophosphate + L-phenylalanyl-tRNA(Phe) PW_R002837 Phenylpyruvic acid + L-Glutamic acid + L-Glutamate > Oxoglutaric acid + L-Phenylalanine + L-Phenylalanine PW_R002861 L-Phenylalanine + Oxygen + L-Phenylalanine <> Oxoglutaric acid + Phenylpyruvic acid PW_R003456 L-Phenylalanine + Oxygen + L-Phenylalanine <> Carbon dioxide + Sinapyl alcohol PW_R003458 Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) <> Adenosine monophosphate + L-Phenylalanyl-tRNA(Phe) + Pyrophosphate alpha-Ketoglutarate + L-Phenylalanine <> L-Glutamate + Phenylpyruvic acid Adenosine triphosphate + L-Phenylalanine + tRNA(Phe) <> Adenosine monophosphate + L-Phenylalanyl-tRNA(Phe) + Pyrophosphate alpha-Ketoglutarate + L-Phenylalanine <> L-Glutamate + Phenylpyruvic acid alpha-Ketoglutarate + L-Phenylalanine <> L-Glutamate + Phenylpyruvic acid Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucose Shake flask and filter culture 18.2 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 72800 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerol Shake flask and filter culture 42.1 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 168400 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetate Shake flask and filter culture 27.4 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 109600 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 48 mM Na2HPO4, 22 mM KH2PO4, 10 mM NaCl, 45 mM (NH4)2SO4, supplemented with 1 mM MgSO4, 1 mg/l thiamine·HCl, 5.6 mg/l CaCl2, 8 mg/l FeCl3, 1 mg/l MnCl2·4H2O, 1.7 mg/l ZnCl2, 0.43 mg/l CuCl2·2H2O, 0.6 mg/l CoCl2·2H2O and 0.6 mg/l Na2MoO4·2H2O. 4 g/L Gluco Bioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h 65.7 uM 0.0 37 oC BW25113 Stationary Phase, glucose limited 262800 0 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776 Luria-Bertani (LB) media Shake flask 51.63 uM true 4.01 37 oC BL21 DE3 Stationary phase cultures (overnight culture) 206533 16027 Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602. 17535911