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MetaCyc Compound: L-ascorbate

Systematic Name: L-ascorbate acid

Synonyms: L-ascorbic acid, ascorbate, vitamin C, ascorbic acid

Superclasses: a vitamin

Summary:
L-ascorbate, also known as vitamin C, fulfils multiple essential roles in both plants and animals. Being a strong reducing agent, it functions as the primary water soluble antioxidant in cells, interacting with reactive oxygen species generated during oxidative stress and protecting cell constituents from oxidative damage [Simpson00]. It also functions as a cofactor for several enzymes, which are involved in many important pathways, including collagen hydroxylation, carnitine biosynthesis, norepinephrine biosynthesis, and hormone and tyrosine metabolism. In plants L-ascorbate is also implicated in defense against pathogens and in control of plant growth and development. A significant proportion of a plant's ascorbate is found in the apoplast (the aqueous solution permeating the cell walls) [Green05].

While most organisms synthesize L-ascorbate, not all do. Examples for organisms that are not able to synthesize L-ascorbate include simians and humans.

Chemical Formula: C6H7O6

Molecular Weight: 175.12 Daltons

Monoisotopic Molecular Weight: 176.0320879894 Daltons

SMILES: C(O)C(O)C1(C([O-])=C(O)C(=O)O1)

InChI: InChI=1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/p-1/t2-,5?/m0/s1

InChIKey: InChIKey=CIWBSHSKHKDKBQ-SZSCBOSDSA-M

Unification Links: CAS:50-81-7 , ChEBI:38290 , ChemSpider:102746 , HMDB:HMDB00044 , IAF1260:33747 , KEGG:C00072 , KNApSAcK:C00001179 , MetaboLights:MTBLC38290 , PubChem:54679076

Standard Gibbs Free Energy of Change Formation (ΔfG in kcal/mol): -146.72423 Inferred by computational analysis [Latendresse13]

Reactions known to consume the compound:

ascorbate glutathione cycle :
2 L-ascorbate + hydrogen peroxide + 2 H+ → 2 monodehydroascorbate radical + 2 H2O

ascorbate recycling (cytosolic) :
L-ascorbate + an oxidized electron acceptor + 2 H+ → monodehydroascorbate radical + a reduced electron acceptor

betaxanthin biosynthesis (via dopaxanthin) :
portulacaxanthin II + L-ascorbate + H+ + oxygen → dopaxanthin + L-dehydro-ascorbate + H2O

catecholamine biosynthesis :
dopamine + L-ascorbate + H+ + oxygen → L-dehydro-ascorbate + (R)-noradrenaline + H2O

ethylene biosynthesis I (plants) :
L-ascorbate + 1-aminocyclopropane-1-carboxylate + H+ + oxygen → ethylene + L-dehydro-ascorbate + hydrogen cyanide + CO2 + 2 H2O

indole glucosinolate breakdown (insect chewing induced) :
indolylmethylisothiocyanate + L-ascorbate → ascorbigen + thiocyanate
indole-3-carbinol + L-ascorbate + H+ → ascorbigen + H2O

L-ascorbate degradation II (bacterial, aerobic) , L-ascorbate degradation III , L-ascorbate degradation V :
2 L-ascorbate + hydrogen peroxide + H+L-ascorbate + L-dehydro-ascorbate + 2 H2O

octopamine biosynthesis :
tyramine + L-ascorbate + oxygen + H+ → octopamine + L-dehydro-ascorbate + H2O

zeaxanthin, antheraxanthin and violaxanthin interconversion :
antheraxanthin + L-ascorbate + H+ → zeaxanthin + L-dehydro-ascorbate + H2O
violaxanthin + L-ascorbate + H+ → antheraxanthin + L-dehydro-ascorbate + H2O

Not in pathways:
L-ascorbate + 2 an oxidized c-type cytochrome → L-dehydro-ascorbate + 2 a reduced c-type cytochrome + H+
L-ascorbate[in] + Fe3+[out] → monodehydroascorbate radical[in] + Fe2+[out]
a C-terminal [protein]-glycine + L-ascorbate + oxygen → a C-terminal [protein]-hydroxyglycine + L-dehydro-ascorbate + H2O
4 L-ascorbate + oxygen + 4 H+ → 4 monodehydroascorbate radical + 2 H2O

Reactions known to produce the compound:

ascorbate glutathione cycle :
L-dehydro-ascorbate + 2 glutathione → L-ascorbate + glutathione disulfide + H+
2 monodehydroascorbate radical + NADPH + H+ → 2 L-ascorbate + NADP+ + 2 H+
2 monodehydroascorbate radical → L-ascorbate + L-dehydro-ascorbate + H+

ascorbate recycling (cytosolic) :
2 monodehydroascorbate radical + NADH → 2 L-ascorbate + NAD+ + H+
L-dehydro-ascorbate + NADPH → L-ascorbate + NADP+
L-dehydro-ascorbate + 2 glutathione → L-ascorbate + glutathione disulfide + H+
2 monodehydroascorbate radical + NADPH + H+ → 2 L-ascorbate + NADP+ + 2 H+
2 monodehydroascorbate radical → L-ascorbate + L-dehydro-ascorbate + H+

L-ascorbate biosynthesis I (L-galactose pathway) :
L-galactono-1,4-lactone + 2 an oxidized c-type cytochrome → L-ascorbate + 2 a reduced c-type cytochrome + 3 H+

L-ascorbate biosynthesis II (L-gulose pathway) :
L-gulono-1,4-lactone + 2 an oxidized c-type cytochrome → L-ascorbate + 2 a reduced c-type cytochrome + 2 H+

L-ascorbate biosynthesis III :
L-sorbosone 1,4-lactone + an oxidized electron acceptor → L-ascorbate + a reduced electron acceptor + H+

L-ascorbate biosynthesis IV :
L-xylo-hex-3-ulono-1,4-lactone → L-ascorbate + H+

L-ascorbate biosynthesis V :
L-galactono-1,4-lactone + an oxidized electron acceptor → L-ascorbate + a reduced electron acceptor + H+

Not in pathways:
2-phospho-L-ascorbate + H2O → L-ascorbate + phosphate
L-galactono-1,4-lactone + oxygen → L-ascorbate + hydrogen peroxide + H+
L-gulono-1,4-lactone + oxygen → L-ascorbate + hydrogen peroxide + H+

Reactions known to both consume and produce the compound:

L-ascorbate biosynthesis VI (engineered pathway) , L-ascorbate degradation IV :
L-ascorbate + H2O ↔ 2-keto-L-gulonate

In Reactions of unknown directionality:

Not in pathways:
violaxanthin + 2 L-ascorbate + 2 H+ = zeaxanthin + 2 L-dehydro-ascorbate + 2 H2O
L-ascorbate + acetyl phosphate = 2-phospho-L-ascorbate + acetate + H+
L-ascorbate + diphosphate = 2-phospho-L-ascorbate + phosphate + H+
a ferricytochrome b5 + L-ascorbate = a ferrocytochrome b5 + monodehydroascorbate radical
L-ascorbate + ATP = 2-phospho-L-ascorbate + ADP + H+

In Transport reactions:
L-ascorbate[extracellular space] + H+[extracellular space]L-ascorbate[cytosol] + H+[cytosol] ,
HPr-Phis15 + L-ascorbate[out] → L-ascorbate 6-phosphate[in] + HPr

In Redox half-reactions:
monodehydroascorbate radical[in] + e-L-ascorbate[in]

Enzymes activated by L-ascorbate, sorted by the type of activation, are:

Activator (Allosteric) of: indole-3-acetaldoxime dehydratase [Shukla68]

Activator (Non-allosteric) of: pyruvic oxime dioxygenase [Ono96]

Activator (Mechanism unknown) of: taurine dioxygenase [Eichhorn97] , naringenin 2-oxoglutarate oxygen oxidoreductase [Lee08b] , deacetoxycephalosporin C synthase [Dotzlaf89] , deacetoxycephalosporin C hydroxylase [Dotzlaf87] , deacetoxycephalosporin C synthase [Dotzlaf87, Baldwin87] , isopenicillin N synthase [Castro88] , tryptophan dioxygenase [Hitchcock88] , gibberellin A15,oxoglutarate:oxygen oxidoreductase [Lange94] , desacetoxyvindoline 4-hydroxylase [De90] , thioglucoside glucohydrolase [Bernardi03] , thioglucoside glucohydrolase [Shikita99] , flavone synthase [Britsch90]

Enzymes inhibited by L-ascorbate, sorted by the type of inhibition, are:

Inhibitor (Mechanism unknown) of: 4-hydrobenzaldehyde synthase [Podstolski02] , [thyroglobulin]-3,5-diiodotyrosine synthase [Coval67] , GDP-D-mannose-3'',5''-epimerase [Wolucka03] , GDP-D-mannose:GDP-L-gulose epimerase [Wolucka03] , phenolase [Sato67]

This compound has been characterized as a cofactor or prosthetic group of the following enzymes: 3-methyl-branched 2,3,4-saturated fatty acyl-CoA hydroxylase , γ-butyrobetaine hydroxylase , ε-N-trimethyllysine hydroxylase , 4-hydroxyphenylpyruvate dioxygenase , 4-hydroxyphenylpyruvate dioxygenase

Credits:
Revised 15-Nov-2012 by Caspi R , SRI International


References

Baldwin87: Baldwin JE, Adlington RM, Coates JB, Crabbe MJ, Crouch NP, Keeping JW, Knight GC, Schofield CJ, Ting HH, Vallejo CA (1987). "Purification and initial characterization of an enzyme with deacetoxycephalosporin C synthetase and hydroxylase activities." Biochem J 245(3);831-41. PMID: 3663194

Bernardi03: Bernardi R, Finiguerra MG, Rossi AA, Palmieri S (2003). "Isolation and biochemical characterization of a basic myrosinase from ripe Crambe abyssinica seeds, highly specific for epi-progoitrin." J Agric Food Chem 51(9);2737-44. PMID: 12696966

Britsch90: Britsch L (1990). "Purification and characterization of flavone synthase I, a 2-oxoglutarate-dependent desaturase." Arch Biochem Biophys 282(1);152-60. PMID: 2221917

Castro88: Castro JM, Liras P, Laiz L, Cortes J, Martin JF (1988). "Purification and characterization of the isopenicillin N synthase of Streptomyces lactamdurans." J Gen Microbiol 134(1);133-41. PMID: 3183613

Coval67: Coval ML, Taurog A (1967). "Purification and iodinating activity of hog thyroid peroxidase." J Biol Chem 242(23);5510-23. PMID: 12325367

De90: De Carolis E, Chan F, Balsevich J, De Luca V (1990). "Isolation and Characterization of a 2-Oxoglutarate Dependent Dioxygenase Involved in the Second-to-Last Step in Vindoline Biosynthesis." Plant Physiol 94(3);1323-1329. PMID: 16667836

Dotzlaf87: Dotzlaf JE, Yeh WK (1987). "Copurification and characterization of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium." J Bacteriol 169(4);1611-8. PMID: 3558321

Dotzlaf89: Dotzlaf JE, Yeh WK (1989). "Purification and properties of deacetoxycephalosporin C synthase from recombinant Escherichia coli and its comparison with the native enzyme purified from Streptomyces clavuligerus." J Biol Chem 264(17);10219-27. PMID: 2656705

Eichhorn97: Eichhorn E, van der Ploeg JR, Kertesz MA, Leisinger T (1997). "Characterization of alpha-ketoglutarate-dependent taurine dioxygenase from Escherichia coli." J Biol Chem 1997;272(37);23031-6. PMID: 9287300

Green05: Green MA, Fry SC (2005). "Vitamin C degradation in plant cells via enzymatic hydrolysis of 4-O-oxalyl-L-threonate." Nature 433(7021);83-7. PMID: 15608627

Hitchcock88: Hitchcock MJ, Katz E (1988). "Purification and characterization of tryptophan dioxygenase from Streptomyces parvulus." Arch Biochem Biophys 261(1);148-60. PMID: 3341771

Lange94: Lange T., Schweimer A., Ward D.A., Hedden P., Graebe J.E. "Separation and characterization of three 2-oxoglutarate-dependent dioxygenases from Cucurbita maxima L. endosperms involved in gibberellin biosynthesis." Planta (1994) 195 : 98-107.

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lee08b: Lee YJ, Kim JH, Kim BG, Lim Y, Ahn JH (2008). "Characterization of flavone synthase I from rice." BMB Rep 41(1);68-71. PMID: 18304453

Ono96: Ono Y, Makino N, Hoshino Y, Shoji K, Yamanaka T (1996). "An iron dioxygenase from Alcaligenes faecalis catalyzing the oxidation of pyruvic oxime to nitrite." FEMS Microbiol Lett 139(2-3);103-8. PMID: 8674977

Podstolski02: Podstolski A, Havkin-Frenkel D, Malinowski J, Blount JW, Kourteva G, Dixon RA (2002). "Unusual 4-hydroxybenzaldehyde synthase activity from tissue cultures of the vanilla orchid Vanilla planifolia." Phytochemistry 61(6);611-20. PMID: 12423881

Sato67: Sato, Mitsuhiko (1967). "Metabolism of phenolic substances by chloroplasts-III. Phenolase as an enzyme concerning the formation of esculetin." Phytochemistry 6:1363-1373.

Shikita99: Shikita M, Fahey JW, Golden TR, Holtzclaw WD, Talalay P (1999). "An unusual case of 'uncompetitive activation' by ascorbic acid: purification and kinetic properties of a myrosinase from Raphanus sativus seedlings." Biochem J 341 ( Pt 3);725-32. PMID: 10417337

Shukla68: Shukla PS, Mahadevan S (1968). "Indoleacetaldoxime hydro-lyase. II. Purification and properties." Arch Biochem Biophys 125(3);873-83. PMID: 5671050

Simpson00: Simpson GL, Ortwerth BJ (2000). "The non-oxidative degradation of ascorbic acid at physiological conditions." Biochim Biophys Acta 1501(1);12-24. PMID: 10727845

Wolucka03: Wolucka BA, Van Montagu M (2003). "GDP-mannose 3',5'-epimerase forms GDP-L-gulose, a putative intermediate for the de novo biosynthesis of vitamin C in plants." J Biol Chem 278(48);47483-90. PMID: 12954627


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC14A.