Escherichia coli K-12 substr. MG1655 Pathway: L-ascorbate degradation II (bacterial, aerobic)

Pathway diagram: L-ascorbate degradation II (bacterial, aerobic)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for L-ascorbate degradation II (bacterial, aerobic)

Superclasses: Degradation/Utilization/AssimilationCarboxylates DegradationL-Ascorbate Degradation

General Background

L-ascorbate, also known as vitamin C, fulfils multiple essential roles in both plants and animals. Being a strong reducing agent, it functions as an antioxidant and a redox buffer. It is also a cofactor for several enzymes, which are involved in many important pathways, including collagen hydroxylation, carnitine biosynthesis, norepinephrine biosynthesis, and hormone and tyrosine metabolism.

Under aerobic conditions L-ascorbate is oxidized in cells to dehydroascorbate (via the radical monodehydroascorbate radical), which can be recycled back to ascorbate by the ascorbate glutathione cycle. However, once formed, dehydroascorbate can be further broken down in vivo by irreversible reactions, escaping the ascorbate glutathione cycle.

Several pathways for the irreversible catabolism of ascorbate have been described. Facultatively aerobic bacteria such as Escherichia coli and Klebsiella pneumoniae degrade L-ascorbate by different pathways under aerobic and anaerobic conditions (see L-ascorbate degradation II (bacterial, aerobic) and L-ascorbate degradation I (bacterial, anaerobic)). 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 [Campos08].

About This Pathway

Under anaerobic conditions Escherichia coli and Klebsiella pneumoniae degrade L-ascorbate via L-ascorbate 6-phosphate utilizing the enzymes encoded by the ula regulon (see L-ascorbate degradation I (bacterial, anaerobic)). Under aerobic conditions L-ascorbate is auto-oxidized to 2,3-dioxo-L-gulonate, which can not be degraded by the anaerobic pathway. A different set of enzymes, encoded by the yiaK-S operon, enables the cells to catabolize L-ascorbate under aerobic conditions as well [Campos08].

The yiaK-S operon, which is controled by the YiaJ repressor, encodes two unique proteins - a reductase ( yiaK) and a kinase ( yiaP) as well as three proteins that are paralogous to ula operon proteins: a carboxylase ( yiaQ) and two epimerases ( yiaS and yiaR) (note tha many of these genes are now known under different names). YiaK and YiaP convert 2,3-dioxo-L-gulonate to 3-keto-L-gulonate 6-phosphate, which can be processed by the rest of the enzymes to D-xylulose 5-phosphate, a centeral metabolite that is fed into the pentose phosphate pathway.

Curiously, the yia regulon is also regulated by L-ascorbate 6-phosphate, a metabolite that can only be produced by the L-ascorbate PTS permease, which is encoded by the ula regulon. Thus, efficient aerobic metabolism of L-ascorbate is dependent on the presence of both systems. In addition, the expression of the yiaK-S operon, but not the expression of the ula regulon, is regulated by oxygen availability. Both systems are regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and by IHF [Campos08].

Variants: L-ascorbate degradation I (bacterial, anaerobic)

Created in MetaCyc 02-Dec-2011 by Caspi R, SRI International
Imported from MetaCyc 14-Dec-2011 by Keseler I, SRI International


Campos08: Campos E, de la Riva L, Garces F, Gimenez R, Aguilar J, Baldoma L, Badia J (2008). "The yiaKLX1X2PQRS and ulaABCDEFG gene systems are required for the aerobic utilization of L-ascorbate in Klebsiella pneumoniae strain 13882 with L-ascorbate-6-phosphate as the inducer." J Bacteriol 190(20);6615-24. PMID: 18708499

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Badia98: Badia J, Ibanez E, Sabate M, Baldoma L, Aguilar J (1998). "A rare 920-kilobase chromosomal inversion mediated by IS1 transposition causes constitutive expression of the yiaK-S operon for carbohydrate utilization in Escherichia coli." J Biol Chem 273(14);8376-81. PMID: 9525947

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Campos07: Campos E, Montella C, Garces F, Baldoma L, Aguilar J, Badia J (2007). "Aerobic L-ascorbate metabolism and associated oxidative stress in Escherichia coli." Microbiology 153(Pt 10);3399-408. PMID: 17906139

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Forouhar04: Forouhar F, Lee I, Benach J, Kulkarni K, Xiao R, Acton TB, Montelione GT, Tong L (2004). "A novel NAD-binding protein revealed by the crystal structure of 2,3-diketo-L-gulonate reductase (YiaK)." J Biol Chem 279(13);13148-55. PMID: 14718529

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Ibanez00: Ibanez E, Gimenez R, Pedraza T, Baldoma L, Aguilar J, Badia J (2000). "Role of the yiaR and yiaS genes of Escherichia coli in metabolism of endogenously formed L-xylulose." J Bacteriol 2000;182(16);4625-7. PMID: 10913097

Ibanez00a: Ibanez E, Campos E, Baldoma L, Aguilar J, Badia J (2000). "Regulation of expression of the yiaKLMNOPQRS operon for carbohydrate utilization in Escherichia coli: involvement of the main transcriptional factors." J Bacteriol 182(16);4617-24. PMID: 10913096

Johnson98: Johnson AE, Tanner ME (1998). "Epimerization via carbon-carbon bond cleavage. L-ribulose-5-phosphate 4-epimerase as a masked class II aldolase." Biochemistry 37(16);5746-54. PMID: 9548961

Kerber08: Kerber, R. C. (2008). ""As simple as possible, but not simpler" - the case of dehydroascorbic acid." J. Chem. Ed. 85(9):1237-1242.

Lee00: Lee LV, Vu MV, Cleland WW (2000). "13C and deuterium isotope effects suggest an aldol cleavage mechanism for L-ribulose-5-phosphate 4-epimerase." Biochemistry 39(16);4808-20. PMID: 10769138

Lee00a: Lee LV, Poyner RR, Vu MV, Cleland WW (2000). "Role of metal ions in the reaction catalyzed by L-ribulose-5-phosphate 4-epimerase." Biochemistry 39(16);4821-30. PMID: 10769139

Lee68: Lee N, Patrick JW, Masson M (1968). "Crystalline L-ribulose 5-phosphate 4-epimerase from Escherichia coli." J Biol Chem 1968;243(18);4700-5. PMID: 4879898

Plantinga04: Plantinga TH, van der Does C, Driessen AJ (2004). "Transporter's evolution and carbohydrate metabolic clusters." Trends Microbiol 12(1);4-7. PMID: 14700544

Samuel01: Samuel J, Luo Y, Morgan PM, Strynadka NC, Tanner ME (2001). "Catalysis and binding in L-ribulose-5-phosphate 4-epimerase: a comparison with L-fuculose-1-phosphate aldolase." Biochemistry 40(49);14772-80. PMID: 11732896

Sanchez94: Sanchez JC, Gimenez R, Schneider A, Fessner WD, Baldoma L, Aguilar J, Badia J (1994). "Activation of a cryptic gene encoding a kinase for L-xylulose opens a new pathway for the utilization of L-lyxose by Escherichia coli." J Biol Chem 1994;269(47);29665-9. PMID: 7961955

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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