| Fumaric acid |
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Other names
trans-1,2-Ethylenedicarboxylic acid
2-Butenedioic acid
trans-butenedioic acid
Allomaleic acid
Boletic acid
Donitic acid
Lichenic acid
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| Identifiers |
| CAS number |
110-17-8 Y |
| ChemSpider |
10197150 Y |
| UNII |
88XHZ13131 Y |
| EC number |
203-743-0 |
| DrugBank |
DB04299 |
| KEGG |
C00122 Y |
| ChEBI |
CHEBI:18012 Y |
| ChEMBL |
CHEMBL503160 Y |
| ATC code |
D05AX01 |
| Jmol-3D images |
Image 1 |
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InChI=1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+ Y
Key: VZCYOOQTPOCHFL-OWOJBTEDSA-N Y
InChI=1/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+
Key: VZCYOOQTPOCHFL-OWOJBTEDBF
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| Properties |
| Molecular formula |
C4H4O4 |
| Molar mass |
116.07 g/mol |
| Appearance |
White solid |
| Density |
1.635 g/cm³, solid |
| Melting point |
287 °C |
| Solubility in water |
0.63 g/100 mL |
| Acidity (pKa) |
pka1 = 3.03, pka2 = 4.44 |
| Hazards |
| EU classification |
Irritant (Xi) |
| R-phrases |
R36 |
| S-phrases |
(S2) S26 |
| NFPA 704 |
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| Related compounds |
| Related carboxylic acids |
maleic acid
succinic acid
crotonic acid |
| Related compounds |
fumaryl chloride
fumaronitrile
dimethyl fumarate
iron(II) fumarate |
Y (verify) (what is: Y/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa) |
| Infobox references |
Fumaric acid or trans-butenedioic acid is the chemical compound with the formula HO2CCH=CHCO2H. This white crystalline compound is one of two isomeric unsaturated dicarboxylic acids, the other being maleic acid. In fumaric acid the carboxylic acid groups are trans (E) and in maleic acid they are cis (Z). Fumaric acid has a fruit-like taste. The salts and esters are known as fumarates. Dimethyl fumarate significantly reduces disability progression in multiple sclerosis.
Contents
- 1 Biology
- 2 Medicine
- 3 Food
- 4 Chemistry
- 5 Other uses
- 6 Safety
- 7 Interactive pathway map
- 8 See also
- 9 References
- 10 External links
Biology[edit]
Fumaric acid is found in fumitory (Fumaria officinalis), bolete mushrooms (specifically Boletus fomentarius var. pseudo-igniarius), lichen, and Iceland moss.
Fumarate is an intermediate in the citric acid cycle used by cells to produce energy in the form of adenosine triphosphate (ATP) from food. It is formed by the oxidation of succinate by the enzyme succinate dehydrogenase. Fumarate is then converted by the enzyme fumarase to malate. Human skin naturally produces fumaric acid when exposed to sunlight.[citation needed]
Fumarate is also a product of the urea cycle.
Medicine[edit]
In patients with relapsing-remitting multiple sclerosis, dimethyl fumarate (BG-12, Biogen) significantly reduced relapse and disability progression in a phase 3 trial. It activates the Nrf2 antioxidant response pathway, the primary cellular defense against the cytotoxic effects of oxidative stress.[1]
Food[edit]
As a food additive, it is used as an acidity regulator and is denoted by the E number E297. Fumaric acid is a food acidulent used since 1946. It is non-toxic. It is generally used in beverages and baking powders for which requirements are placed on purity. It is generally used as a substitute for tartaric acid and occasionally in place of citric acid, at a rate of 1.36 g of citric acid to every 0.91 grams of fumaric acid to add sourness, similar to the way malic acid is used. It is also used as a coagulant in stovetop pudding mixes.
It is approved for use as a food additive in the EU,[2] USA[3] and Australia and New Zealand[4] (where it is listed by its INS number 297).
Chemistry[edit]
Fumaric acid was first prepared from succinic acid.[5] A traditional synthesis involves oxidation of furfural (from the processing of maize) using chlorate in the presence of a vanadium-based catalyst.[6] Currently, industrial synthesis of fumaric acid is mostly based on catalytic isomerisation of maleic acid in aqueous solutions at low pH. Maleic acid is accessible in large volumes as a hydrolysis product of maleic anhydride, produced by catalytic oxidation of benzene or butane.[7]
The chemical properties of fumaric acid can be anticipated from its component functional groups. This weak acid forms a diester, it undergoes additions across the double bond, and it is an excellent dienophile.
Fumaric acid does not combust in a bomb calorimeter under conditions where maleic acid deflagrates smoothly. For teaching experiments designed to measure the difference in energy between the cis- and trans- isomers, a measured quantity of carbon can be ground with the subject compound and the enthalpy of combustion computed by difference.
Other uses[edit]
Fumaric acid is used in the manufacture of polyester resins and polyhydric alcohols and as a mordant for dyes.
Safety[edit]
Fumaric acid converts to the irritant maleic anhydride, upon partial combustion.
Interactive pathway map[edit]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".
See also[edit]
- Dermatology
- Photosynthesis
- Maleic acid, the cis-isomer of fumaric acid
References[edit]
- ^ Gold R., Kappos L., Arnold D.L., et al. (September 20, 2012). "Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis". N Engl J Med 367: 1098–1107.
- ^ UK Food Standards Agency: "Current EU approved additives and their E Numbers". Retrieved 2011-10-27.
- ^ US Food and Drug Administration: "Listing of Food Additives Status Part II". Retrieved 2011-10-27.
- ^ Australia New Zealand Food Standards Code"Standard 1.2.4 - Labelling of ingredients". Retrieved 2011-10-27.
- ^ Volhard, J. "Darstellung von Maleïnsäureanhydrid" Justus Liebig's Annalen der Chemie 1892, volume 268, page 255-6. doi:10.1002/jlac.18922680108
- ^ Milas, N. A. "Fumaric Acid" Organic Synthesis 1943, Collective Volume 2, page 302. Online version
- ^ British Patent No. 775,912, publicated on the May 29, 1957, by Monsanto Chemical Company.
External links[edit]
- International Chemical Safety Card 1173
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Citric Acid Cycle Metabolic Pathway |
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Oxaloacetate |
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Malate |
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Fumarate |
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Succinate |
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Succinyl-CoA |
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| Acetyl-CoA |
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NADH + H+ |
NAD+ |
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H2O |
FADH2 |
FAD |
CoA + ATP(GTP) |
Pi + ADP(GDP) |
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+ |
H2O |
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NADH + H+ + CO2 |
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CoA |
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NAD+ |
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H2O |
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H2O |
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NAD(P)+ |
NAD(P)H + H+ |
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CO2 |
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Citrate |
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cis-Aconitate |
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Isocitrate |
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Oxalosuccinate |
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α-Ketoglutarate |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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Urea cycle Metabolic Pathway |
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L-citrulline |
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Carbamoyl
phosphate |
L-ornithine |
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Pi |
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| L-aspartate |
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Urea |
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ATP |
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| PPi |
+ |
AMP |
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H2O |
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L-argininosuccinate |
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Fumarate |
L-arginine |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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Antipsoriatics (D05)
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| Topical |
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Tars
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Antracens
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Psoralens
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Other
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- Fumaric acid
- vitamin D (Calcipotriol
- Calcipotriol/betamethasone
- Calcitriol
- Tacalcitol)
- Tazarotene
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| Systemic |
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Psoralens
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- Trioxysalen
- Methoxsalen
- Bergapten
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Retinoids
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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noco (i/b/d/q/u/r/p/m/k/v/f)/cong/tumr (n/e/d), sysi/epon
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proc, drug (D2/3/4/5/8/11)
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Amino acid metabolism metabolic intermediates
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| K→acetyl-CoA |
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lysine→
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- Saccharopine
- Allysine
- α-Aminoadipic acid
- α-Aminoadipate
- Glutaryl-CoA
- Glutaconyl-CoA
- Crotonyl-CoA
- β-Hydroxybutyryl-CoA
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leucine→
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- α-Ketoisocaproic acid
- Isovaleryl-CoA
- 3-Methylcrotonyl-CoA
- 3-Methylglutaconyl-CoA
- HMG-CoA
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tryptophan→alanine→
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- N'-Formylkynurenine
- Kynurenine
- Anthranilic acid
- 3-Hydroxykynurenine
- 3-Hydroxyanthranilic acid
- 2-Amino-3-carboxymuconic semialdehyde
- 2-Aminomuconic semialdehyde
- 2-Aminomuconic acid
- Glutaryl-CoA
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| G |
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G→pyruvate→citrate
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glycine→serine→
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- glycine→creatine: Glycocyamine
- Phosphocreatine
- Creatinine
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G→glutamate→
α-ketoglutarate
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histidine→
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- Urocanic acid
- Imidazol-4-one-5-propionic acid
- Formiminoglutamic acid
- Glutamate-1-semialdehyde
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proline→
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- 1-Pyrroline-5-carboxylic acid
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arginine→
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- Ornithine
- Putrescine
- Agmatine
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other
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- cysteine+glutamate→glutathione: γ-Glutamylcysteine
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G→propionyl-CoA→
succinyl-CoA
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valine→
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- α-Ketoisovaleric acid
- Isobutyryl-CoA
- Methacrylyl-CoA
- 3-Hydroxyisobutyryl-CoA
- 3-Hydroxyisobutyric acid
- 2-Methyl-3-oxopropanoic acid
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isoleucine→
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- 2,3-Dihydroxy-3-methylpentanoic acid
- 2-Methylbutyryl-CoA
- Tiglyl-CoA
- 2-Methylacetoacetyl-CoA
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methionine→
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- generation of homocysteine: S-Adenosyl methionine
- S-Adenosyl-L-homocysteine
- Homocysteine
- conversion to cysteine: Cystathionine
- alpha-Ketobutyric acid+Cysteine
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threonine→
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propionyl-CoA→
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G→fumarate
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phenylalanine→tyrosine→
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- 4-Hydroxyphenylpyruvic acid
- Homogentisic acid
- 4-Maleylacetoacetate
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G→oxaloacetate
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| Other |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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- Biochemical families: carbohydrates
- alcohols
- glycoproteins
- glycosides
- lipids
- eicosanoids
- fatty acids / intermediates
- phospholipids
- sphingolipids
- steroids
- nucleic acids
- constituents / intermediates
- proteins
- Amino acids / intermediates
- tetrapyrroles / intermediates
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