2.02012-05-31 09:56:31 -06002015-09-13 12:56:05 -0600ECMDB00062M2MDB000023CarnitineCarnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids during the breakdown of lipids (fats) for the generation of metabolic energy. Carnitine was originally found as a growth factor for mealworms and labeled vitamin Bt. Carnitine exists in two stereoisomers: Its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive. E. coli converts carnitine, via crotonobetaine, to gamma-butyrobetaine in the presence of C and N sources and under anaerobic conditions. This two-step pathway requires L-(-)-carnitine dehydratase and crotonobetaine reductase. Anaerobic carnitine metabolism in Escherichia coli involves six genes organized in the cai operon and located at the first minute on the E. coli chromosome. γ-Trimethyl-hydroxybutyrobetaine(-)-(R)-3-Hydroxy-4-(trimethylammonio)butyrate(-)-(R)-3-Hydroxy-4-(trimethylammonio)butyric acid(-)-Carnitine(-)-L-Carnitine(3-carboxy-2-hydroxypropyl)trimethyl-Ammonium hydroxide inner salt(R)-(3-Carboxy-2-hydroxypropyl)trimethylammonium hydroxide(R)-Carnitine(S)-carnitine1-carnitine3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-Propanaminium hydroxide inner salt3-Hydroxy-4-trimethylammoniobutanoate3-Hydroxy-4-trimethylammoniobutanoic acidBicarnesineCarnikingCarniking 50CarnileanCarnipassCarnipass 20CarniteneCarnitine (L-form)CarnitorCarnitor, LevocarnitineD-carnitineDelta-carnitineDl-carnitineg-Trimethyl-ammonium-b-hydroxybutirateg-Trimethyl-ammonium-b-hydroxybutiric acidg-Trimethyl-b-hydroxybutyrobetaineg-Trimethyl-hydroxybutyrobetaineGamma-trimethyl-ammonium-beta-hydroxybutirategamma-Trimethyl-ammonium-beta-hydroxybutiric acidGamma-trimethyl-beta-hydroxybutyrobetaineGamma-Trimethyl-hydroxybutyrobetaineKarnitinL-γ-trimethyl-β-hydroxybutyrobetaineL-(-)-CarnitineL-CarnitineL-g-Trimethyl-b-hydroxybutyrobetaineL-gamma-Trimethyl-beta-hydroxybutyrobetaineL-γ-Trimethyl-β-hydroxybutyrobetaineLevocarnitinaLevocarnitineLevocarnitine chlorideLevocarnitinumR-(-)-3-Hydroxy-4-trimethylaminobutyrateR-(-)-3-Hydroxy-4-trimethylaminobutyric acidVitamin B TVitamin Btγ-Trimethyl-ammonium-β-hydroxybutirateγ-Trimethyl-ammonium-β-hydroxybutiric acidγ-Trimethyl-hydroxybutyrobetaineγ-Trimethyl-β-hydroxybutyrobetaineδ-CarnitineC7H16NO3162.2068162.113018383(3-carboxy-2-hydroxypropyl)trimethylazaniumcarnitina541-15-1C[N+](C)(C)CC(O)CC(O)=OInChI=1S/C7H15NO3/c1-8(2,3)5-6(9)4-7(10)11/h6,9H,4-5H2,1-3H3/p+1PHIQHXFUZVPYII-UHFFFAOYSA-OSolidCytosolExtra-organismPeriplasmlogp-2.75logs-1.48solubility6.58e+00 g/lmelting_point210-212 oClogp-4.9pka_strongest_acidic4.2pka_strongest_basic-3.6iupac(3-carboxy-2-hydroxypropyl)trimethylazaniumaverage_mass162.2068mono_mass162.113018383smilesC[N+](C)(C)CC(O)CC(O)=OformulaC7H16NO3inchiInChI=1S/C7H15NO3/c1-8(2,3)5-6(9)4-7(10)11/h6,9H,4-5H2,1-3H3/p+1inchikeyPHIQHXFUZVPYII-UHFFFAOYSA-Opolar_surface_area57.53refractivity52.65polarizability17.18rotatable_bond_count4acceptor_count3donor_count2physiological_charge0formal_charge1Lysine degradationec00310ABC transportersec02010carnitine degradation ICARNMET-PWYSpecdb::CMs81530Specdb::NmrOneD290935Specdb::NmrOneD290936Specdb::NmrOneD290937Specdb::NmrOneD290938Specdb::NmrOneD290939Specdb::NmrOneD290940Specdb::NmrOneD290941Specdb::NmrOneD290942Specdb::NmrOneD290943Specdb::NmrOneD290944Specdb::NmrOneD290945Specdb::NmrOneD290946Specdb::NmrOneD290947Specdb::NmrOneD290948Specdb::NmrOneD290949Specdb::NmrOneD290950Specdb::NmrOneD290951Specdb::NmrOneD290952Specdb::NmrOneD290953Specdb::NmrOneD290954Specdb::MsMs1007744Specdb::MsMs1007745Specdb::MsMs1007746HMDB000621091783C0048717126CARNITINEL-CarnitineKeseler, 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-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, 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 80:2939-2948.18331064Canovas, M., Bernal, V., Sevilla, A., Iborra, J. L. (2007). "Salt stress effects on the central and carnitine metabolisms of Escherichia coli." Biotechnol Bioeng 96:722-737.16894634Ishii, 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 316:593-597.17379776http://hmdb.ca/system/metabolites/msds/000/000/045/original/HMDB00062.pdf?1358894663Glycine betaine/L-proline transport ATP-binding protein proVP14175PROV_ECOLIproVhttp://ecmdb.ca/proteins/P14175.xmlCrotonobetainyl-CoA:carnitine CoA-transferaseP31572CAIB_ECOLIcaiBhttp://ecmdb.ca/proteins/P31572.xmlGlycine betaine/L-proline transport system permease protein proWP14176PROW_ECOLIproWhttp://ecmdb.ca/proteins/P14176.xmlProbable crotonobetaine/carnitine-CoA ligaseP31552CAIC_ECOLIcaiChttp://ecmdb.ca/proteins/P31552.xmlGlycine betaine-binding periplasmic proteinP0AFM2PROX_ECOLIproXhttp://ecmdb.ca/proteins/P0AFM2.xmlProline/betaine transporterP0C0L7PROP_ECOLIproPhttp://ecmdb.ca/proteins/P0C0L7.xmlGlycine betaine/L-proline transport system permease protein proWP14176PROW_ECOLIproWhttp://ecmdb.ca/proteins/P14176.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlL-carnitine/gamma-butyrobetaine antiporterP31553CAIT_ECOLIcaiThttp://ecmdb.ca/proteins/P31553.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlAdenosine triphosphate + Water + Carnitine > ADP + Carnitine + Hydrogen ion + PhosphateAdenosine triphosphate + Water + Carnitine > ADP + Carnitine + Hydrogen ion + PhosphateAdenosine triphosphate + Coenzyme A + Carnitine > ADP + L-Carnitinyl-CoA + PhosphateAdenosine triphosphate + Coenzyme A + Carnitine > ADP + D-Carnitinyl-CoA + PhosphateCarnitine + Crotonobetainyl-CoA <> L-Carnitinyl-CoA + Crotonobetainegamma-Butyrobetainyl-CoA + Carnitine <> L-Carnitinyl-CoA + gamma-ButyrobetaineRXN0-3601Coenzyme A + Carnitine + Adenosine triphosphate > L-Carnitinyl-CoA + Adenosine monophosphate + PyrophosphateLCARNCOALIG-RXNCarnitine + gamma-Butyrobetainyl-CoA > L-Carnitinyl-CoA + gamma-ButyrobetaineRXN0-360148 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 GlucoBioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h3.99uM0.037 oCBW25113Stationary Phase, glucose limited159600Ishii, 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