2.02012-05-31 14:08:05 -06002015-06-03 15:54:51 -0600ECMDB06334M2MDB0006653-Dehydro-L-gulonate3-Dehydro-L-gulonate is an intermediate in ascorbic acid degradation. It is a substrate for the enzyme 2,3-diketo-L-gulonate reductase. This enzyme catalyzes the reduction of 2,3-diketo-L-gulonate in the presence of NADH, to form 3-keto-L-gulonate. It participates in the reaction: 3-dehydro-L-gulonate + NAD(P)+ = (4R,5S)-4,5,6-trihydroxy-2,3-dioxohexanoate + NAD(P)H. Several pathways for the irreversible catabolism of ascorbate have been described. Facultatively aerobic bacteria such as Escherichia coli degrade L-ascorbate by different pathways under aerobic and anaerobic conditions. The anaerobic pathway begins with phosphorylation of ascorbate (mediated by a PTS-type transporter), while the aerobic pathway proceeds via 2,3-dioxo-L-gulonate. Both pathways produce D-xylulose 5-phosphate, a centeral metabolite that is fed into the pentose phosphate pathway.3-Dehydro-L-gulonate3-Dehydro-L-gulonic acidL-Xylo-hex-3-ulosonateL-Xylo-hex-3-ulosonic acidC6H10O7194.1394194.042652674(2S,4R,5S)-2,4,5,6-tetrahydroxy-3-oxohexanoic acid3-dehydro-L-gulonic acidOC[C@H](O)[C@@H](O)C(=O)[C@H](O)C(O)=OInChI=1S/C6H10O7/c7-1-2(8)3(9)4(10)5(11)6(12)13/h2-3,5,7-9,11H,1H2,(H,12,13)/t2-,3+,5-/m0/s1WTAHRPBPWHCMHW-LWKDLAHASA-NSolidCytosollogp-2.56logs-0.27solubility1.05e+02 g/llogp-2.6pka_strongest_acidic3.16pka_strongest_basic-3iupac(2S,4R,5S)-2,4,5,6-tetrahydroxy-3-oxohexanoic acidaverage_mass194.1394mono_mass194.042652674smilesOC[C@H](O)[C@@H](O)C(=O)[C@H](O)C(O)=OformulaC6H10O7inchiInChI=1S/C6H10O7/c7-1-2(8)3(9)4(10)5(11)6(12)13/h2-3,5,7-9,11H,1H2,(H,12,13)/t2-,3+,5-/m0/s1inchikeyWTAHRPBPWHCMHW-LWKDLAHASA-Npolar_surface_area135.29refractivity37.58polarizability16.3rotatable_bond_count5acceptor_count7donor_count5physiological_charge-1formal_charge0Ascorbate and aldarate metabolismec00053Pentose and glucuronate interconversionsec00040Ascorbate metabolismE. coli is able to utilize L-ascorbate (vitamin C) as the sole source of carbon under anaerobic and aerobic conditions.
Ascorbic acid in the cytoplasm is processed through a spontaneous reaction with a hydrogen ion and hydrogen peroxide, producing water, dehydroascorbic acid and ascorbic acid. Dehydroascorbic acid reacts with water spontaneously producing an isomer, dehydroascorbate (bicyclic form). The compound then loses a hydrogen ion resulting in a 2,3-Diketo-L-gulonate. This compound is then reduced through a NADH dependent 2,3 diketo-L-gulonate reductase, releasing a NAD and 3-Dehydro-L-gulonate.This compound is phosphorylated through an ATP mediated L-xylulose/3-keto-L-gulonate kinase resulting in an ADP, hydrogen ion and a 3-Keto-L-gulonate 6 phosphate.
L-ascorbate can also be imported and converted to L-ascorbate-6-phosphate by the L-ascorbate PTS transporter. L-ascorbate-6-phosphate reacts with a probable L-ascorbate-6-phosphate lactonase ulaG, resulting in a 3-keto-L-gulonate 6-phosphate.
The compound 3-keto-L-gulonate 6-phosphate can be processed aerobically or anaerobically.
Aerobic:
3-keto-L-gulonate 6-phosphate is decarboxylated by a 3-keto-L-gulonate-6-phosphate decarboxylase ulaD, releasing carbon dioxide and L-xylulose-5-phosphate. This compound in turn is changed into an isomer by L-ribulose-5-phosphate 3-epimerase ulaE, resulting in L-ribulose 5-phosphate. This compound again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase ulaF resulting in Xylulose 5-phosphate. This compound can then be part of the pentose phosphate pathway.
Anaerobic:
3-keto-L-gulonate 6-phosphate is decarboxylated by 3-keto-L-gulonate 6-phosphate decarboxylase sgbH, releasing carbon dioxide and L-xylulose-5-phosphate. This compound in turn is changed into an isomer by predicted L-xylulose 5-phosphate 3-epimerase, resulting in L-ribulose 5-phosphate. This compound again changes into a different isomer through a L-ribulose-5-phosphate 4-epimerase resulting in Xylulose 5-phosphate. This compound can then be part of the pentose phosphate pathway.
Expression of the ula regulon is regulated by the L-ascorbate 6-phosphate-binding repressor UlaR and by cAMP-CRP.
Under aerobic conditions, metabolism of L-ascorbate is hindered by the special reactivity and toxicity of this compound in the presence of oxygen.PW000793MetabolicL-ascorbate degradation II (bacterial, aerobic)PWY-6961Specdb::CMs20889Specdb::CMs39002Specdb::CMs169797Specdb::NmrOneD150160Specdb::NmrOneD150161Specdb::NmrOneD150162Specdb::NmrOneD150163Specdb::NmrOneD150164Specdb::NmrOneD150165Specdb::NmrOneD150166Specdb::NmrOneD150167Specdb::NmrOneD150168Specdb::NmrOneD150169Specdb::NmrOneD150170Specdb::NmrOneD150171Specdb::NmrOneD150172Specdb::NmrOneD150173Specdb::NmrOneD150174Specdb::NmrOneD150175Specdb::NmrOneD150176Specdb::NmrOneD150177Specdb::NmrOneD150178Specdb::NmrOneD150179Specdb::MsMs26864Specdb::MsMs26865Specdb::MsMs26866Specdb::MsMs33422Specdb::MsMs33423Specdb::MsMs33424Specdb::MsMs2421678Specdb::MsMs2421679Specdb::MsMs2421680Specdb::MsMs2513450Specdb::MsMs2513451Specdb::MsMs2513452HMDB06334439273388406C006183-KETO-L-GULONATEKeseler, 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-D114.220805102,3-diketo-L-gulonate reductaseP37672DLGD_ECOLIdlgDhttp://ecmdb.ca/proteins/P37672.xmlL-xylulose/3-keto-L-gulonate kinaseP37677LYXK_ECOLIlyxhttp://ecmdb.ca/proteins/P37677.xml2,3-Diketo-L-gulonate + Hydrogen ion + NADH > 3-Dehydro-L-gulonate + NADR02637RXN0-7033-Dehydro-L-gulonate + Adenosine triphosphate > 3-Dehydro-L-gulonate 6-phosphate + ADP + Hydrogen ionR07127RXN0-7043-Dehydro-L-gulonate + NAD <> 2,3-Diketo-L-gulonate + NADH + Hydrogen ionR026373-Dehydro-L-gulonate + NADP <> 2,3-Diketo-L-gulonate + NADPH + Hydrogen ionR026393-Dehydro-L-gulonate + Adenosine triphosphate <> 3-Dehydro-L-gulonate 6-phosphate + ADPR071273-Dehydro-L-gulonate + NAD < Hydrogen ion + 2,3-Diketo-L-gulonate + NADHRXN0-7033-Dehydro-L-gulonate + NAD(P)(+) > (4R,5S)-4,5,6-trihydroxy-2,3-dioxohexanoate + NAD(P)HAdenosine triphosphate + 3-Dehydro-L-gulonate > ADP + 3-Dehydro-L-gulonate 6-phosphate3-Dehydro-L-gulonate + NAD + NADP <> 2,3-Diketo-L-gulonate + NADH + NADPH + Hydrogen ionR02637 R02639 3-Dehydro-L-gulonate + Adenosine triphosphate > 3-keto-L-gulonate 6-phosphate + Adenosine diphosphate + Hydrogen ion + 3-Keto-L-gulonate 6-phosphate + ADPPW_R0026972,3-Diketo-L-gulonate + NADH + Hydrogen ion + 2,3-Diketo-L-gulonate > 3-Dehydro-L-gulonate + NADPW_R002698