Fumaric acid

Last updated
Fumaric acid
Skeletal formula of fumaric acid Fumaric-acid-2D-skeletal.png
Skeletal formula of fumaric acid
Ball-and-stick model of the fumaric acid molecule Fumaric-acid-3D-balls.png
Ball-and-stick model of the fumaric acid molecule
Names
Preferred IUPAC name
(2E)-But-2-enedioic acid
Other names
  • Fumaric acid
  • trans-1,2-Ethylenedicarboxylic acid
  • 2-Butenedioic acid
  • trans-Butenedioic acid
  • Allomaleic acid
  • Boletic acid
  • Donitic acid
  • Lichenic acid
Identifiers
3D model (JSmol)
605763
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.003.404 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 203-743-0
E number E297 (preservatives)
49855
KEGG
PubChem CID
RTECS number
  • LS9625000
UNII
UN number 9126
  • InChI=1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+ Yes check.svgY
    Key: VZCYOOQTPOCHFL-OWOJBTEDSA-N Yes check.svgY
  • InChI=1/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+
    Key: VZCYOOQTPOCHFL-OWOJBTEDBF
  • C(=C/C(=O)O)\C(=O)O
Properties
C4H4O4
Molar mass 116.072 g·mol−1
AppearanceWhite solid
Density 1.635 g/cm3
Melting point 287 °C (549 °F; 560 K) (decomposes) [1]
6.3 g/L at 25 °C [2]
Acidity (pKa)pka1 = 3.03, pka2 = 4.44 (15 °C, cis isomer)
−49.11·10−6 cm3/mol
non zero
Pharmacology
D05AX01 ( WHO )
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H319
P264, P280, P305+P351+P338, P313
NFPA 704 (fire diamond)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
375 °C (707 °F; 648 K)
Related compounds
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Fumaric acid or trans-butenedioic acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297. [3] The salts and esters are known as fumarates. Fumarate can also refer to the C
4
H
2
O2−
4
ion (in solution). Fumaric acid is the trans isomer of butenedioic acid, while maleic acid is the cis isomer.

Contents

Biosynthesis and occurrence

It is produced in eukaryotic organisms from succinate in complex 2 of the electron transport chain via the enzyme succinate dehydrogenase.

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. [4] [5]

Fumarate is also a product of the urea cycle.

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

[[File:
TCACycle WP78.png Go to articleGo to articleGo to articleGo to articleGo to HMDBGo to articleGo to articleGo to articleGo to HMDBGo to HMDBGo to articleGo to WikiPathwaysGo to articleGo to articleGo to articleGo to WikiPathwaysGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to WikiPathwaysGo to articleGo to articleGo to articleGo to HMDBGo to articleGo to articleGo to articleGo to articleGo to articleGo to WikiPathwaysGo to articleGo to WikiPathwaysGo to HMDBGo to articleGo to WikiPathwaysGo to articleGo to HMDBGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to article
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
TCACycle WP78.png Go to articleGo to articleGo to articleGo to articleGo to HMDBGo to articleGo to articleGo to articleGo to HMDBGo to HMDBGo to articleGo to WikiPathwaysGo to articleGo to articleGo to articleGo to WikiPathwaysGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to WikiPathwaysGo to articleGo to articleGo to articleGo to HMDBGo to articleGo to articleGo to articleGo to articleGo to articleGo to WikiPathwaysGo to articleGo to WikiPathwaysGo to HMDBGo to articleGo to WikiPathwaysGo to articleGo to HMDBGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to articleGo to article
|alt=TCACycle_WP78 edit]]
TCACycle_WP78 edit
  1. The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".

Uses

Food

Fumaric acid has been used as a food acidulant since 1946. It is approved for use as a food additive in the EU, [6] USA [7] and Australia and New Zealand. [8] As a food additive, it is used as an acidity regulator and can be denoted by the E number E297. It is generally used in beverages and baking powders for which requirements are placed on purity. Fumaric acid is used in the making of wheat tortillas as a food preservative and as the acid in leavening. [9] It is generally used as a substitute for tartaric acid and occasionally in place of citric acid, at a rate of 1 g of fumaric acid to every ~1.5 g of citric acid, in order to add sourness, similarly to the way malic acid is used. As well as being a component of some artificial vinegar flavors, such as "Salt and Vinegar" flavored potato chips, [10] it is also used as a coagulant in stove-top pudding mixes.

The European Commission Scientific Committee on Animal Nutrition, part of DG Health, found in 2014 that fumaric acid is "practically non-toxic" but high doses are probably nephrotoxic after long-term use. [11]

Medicine

Fumaric acid was developed as a medicine to treat the autoimmune condition psoriasis in the 1950s in Germany as a tablet containing 3 esters, primarily dimethyl fumarate, and marketed as Fumaderm by Biogen Idec in Europe. Biogen would later go on to develop the main ester, dimethyl fumarate, as a treatment for multiple sclerosis.

In patients with relapsing-remitting multiple sclerosis, the ester 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. [12]

Other uses

Fumaric acid is used in the manufacture of polyester resins and polyhydric alcohols and as a mordant for dyes.

Fumaric acid can be used to make 6-methylcoumarin. [13]

When fumaric acid is added to their feed, lambs produce up to 70% less methane during digestion. [14]

Synthesis

Fumaric acid is produced based on catalytic isomerisation of maleic acid in aqueous solutions at low pH. It precipitates from the reaction solution. Maleic acid is accessible in large volumes as a hydrolysis product of maleic anhydride, produced by catalytic oxidation of benzene or butane. [3]

Historic and laboratory routes

Fumaric acid was first prepared from succinic acid. [15] A traditional synthesis involves oxidation of furfural (from the processing of maize) using chlorate in the presence of a vanadium-based catalyst. [16]

Reactions

The chemical properties of fumaric acid can be anticipated from its component functional groups. This weak acid forms a diester, it undergoes bromination across the double bond, [17] and it is a good dienophile.

Safety

The oral LD50 is 10g/kg. [3]

See also

Related Research Articles

<span class="mw-page-title-main">Citric acid cycle</span> Interconnected biochemical reactions releasing energy

The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle —is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, proteins, and alcohol. The chemical energy released is available in the form of ATP. The Krebs cycle is used by organisms that respire to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a "cycle", it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.

A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by undesirable chemical changes. In general, preservation is implemented in two modes, chemical and physical. Chemical preservation entails adding chemical compounds to the product. Physical preservation entails processes such as refrigeration or drying. Preservative food additives reduce the risk of foodborne infections, decrease microbial spoilage, and preserve fresh attributes and nutritional quality. Some physical techniques for food preservation include dehydration, UV-C radiation, freeze-drying, and refrigeration. Chemical preservation and physical preservation techniques are sometimes combined.

<span class="mw-page-title-main">Citric acid</span> Weak organic acid

Citric acid is an organic compound with the formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the metabolism of all aerobic organisms.

<span class="mw-page-title-main">Succinic acid</span> Dicarboxylic acid

Succinic acid is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state.

<span class="mw-page-title-main">Malic acid</span> Dicarboxylic acid responsible for apple acidity

Malic acid is an organic compound with the molecular formula HO2CCH(OH)CH2CO2H. It is a dicarboxylic acid that is made by all living organisms, contributes to the sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms, though only the L-isomer exists naturally. The salts and esters of malic acid are known as malates. The malate anion is a metabolic intermediate in the citric acid cycle.

<span class="mw-page-title-main">Malonic acid</span> Carboxylic acid with chemical formula CH2(COOH)2

Malonic acid is a dicarboxylic acid with structure CH2(COOH)2. The ionized form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic acid's diethyl ester. The name originates from the Greek word μᾶλον (malon) meaning 'apple'.

<span class="mw-page-title-main">Oxaloacetic acid</span> Organic compound

Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle.

<span class="mw-page-title-main">Soured milk</span> Milk-based food product

Soured milk denotes a range of food products produced by the acidification of milk. Acidification, which gives the milk a tart taste, is achieved either through bacterial fermentation or through the addition of an acid, such as lemon juice or vinegar. The acid causes milk to coagulate and thicken, inhibiting the growth of harmful bacteria and improving the product's shelf life.

<span class="mw-page-title-main">Maleic acid</span> Dicarboxylic acid

Maleic acid or cis-butenedioic acid is an organic compound that is a dicarboxylic acid, a molecule with two carboxyl groups. Its chemical formula is HO2CCH=CHCO2H. Maleic acid is the cis isomer of butenedioic acid, whereas fumaric acid is the trans isomer. Maleic acid is mainly used as a precursor to fumaric acid, and relative to its parent maleic anhydride, which has many applications.

<span class="mw-page-title-main">Mixed acid fermentation</span> Biochemical conversion of six-carbon sugars into acids in bacteria

In biochemistry, mixed acid fermentation is the metabolic process by which a six-carbon sugar is converted into a complex and variable mixture of acids. It is an anaerobic (non-oxygen-requiring) fermentation reaction that is common in bacteria. It is characteristic for members of the Enterobacteriaceae, a large family of Gram-negative bacteria that includes E. coli.

Polyester resins are synthetic resins formed by the reaction of dibasic organic acids and polyhydric alcohols. Maleic anhydride is a commonly used raw material with diacid functionality in unsaturated polyester resins. Unsaturated polyester resins are used in sheet moulding compound, bulk moulding compound and the toner of laser printers. Wall panels fabricated from polyester resins reinforced with fiberglass—so-called fiberglass reinforced plastic (FRP)—are typically used in restaurants, kitchens, restrooms and other areas that require washable low-maintenance walls. They are also used extensively in cured-in-place pipe applications. Departments of Transportation in the USA also specify them for use as overlays on roads and bridges. In this application they are known AS Polyester Concrete Overlays (PCO). These are usually based on isophthalic acid and cut with styrene at high levels—usually up to 50%. Polyesters are also used in anchor bolt adhesives though epoxy based materials are also used. Many companies have and continue to introduce styrene free systems mainly due to odor issues, but also over concerns that styrene is a potential carcinogen. Drinking water applications also prefer styrene free. Most polyester resins are viscous, pale coloured liquids consisting of a solution of a polyester in a reactive diluent which is usually styrene, but can also include vinyl toluene and various acrylates.

Isocitric acid is a structural isomer of citric acid. Since citric acid and isocitric acid are structural isomers, they share similar physical and chemical properties. Due to these similar properties, it is difficult to separate the isomers. Salts and esters of isocitric acid are known as isocitrates. The isocitrate anion is a substrate of the citric acid cycle. Isocitrate is formed from citrate with the help of the enzyme aconitase, and is acted upon by isocitrate dehydrogenase.

<span class="mw-page-title-main">Maleate isomerase</span> Member of the Asp/Glu racemase superfamily

In enzymology, a maleate isomerase, or maleate cis-tran isomerase, is a member of the Asp/Glu racemase superfamily discovered in bacteria. It is responsible for catalyzing cis-trans isomerization of the C2-C3 double bond in maleate to produce fumarate, which is a critical intermediate in citric acid cycle. The presence of an exogenous mercaptan is required for catalysis to happen.

<span class="mw-page-title-main">Succinate—CoA ligase (GDP-forming)</span>

In enzymology, a succinate—CoA ligase (GDP-forming) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Dimethyl fumarate</span> Chemical compound

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and is named after the earth smoke plant. Dimethyl fumarate combined with three other fumaric acid esters (FAEs) is solely licensed in Germany as an oral therapy for psoriasis. Since 2013, it has been approved by the U.S. Food and Drug Administration (FDA) as a treatment option for adults with relapsing multiple sclerosis. In 2017, an oral formulation of dimethyl fumarate was approved for medical use in the European Union as a treatment for moderate-to-severe plaque psoriasis. Dimethyl fumarate is thought to have immunomodulatory properties without causing significant immunosuppression.

<span class="mw-page-title-main">Acids in wine</span>

The acids in wine are an important component in both winemaking and the finished product of wine. They are present in both grapes and wine, having direct influences on the color, balance and taste of the wine as well as the growth and vitality of yeast during fermentation and protecting the wine from bacteria. The measure of the amount of acidity in wine is known as the “titratable acidity” or “total acidity”, which refers to the test that yields the total of all acids present, while strength of acidity is measured according to pH, with most wines having a pH between 2.9 and 3.9. Generally, the lower the pH, the higher the acidity in the wine. There is no direct connection between total acidity and pH. In wine tasting, the term “acidity” refers to the fresh, tart and sour attributes of the wine which are evaluated in relation to how well the acidity balances out the sweetness and bitter components of the wine such as tannins. Three primary acids are found in wine grapes: tartaric, malic, and citric acids. During the course of winemaking and in the finished wines, acetic, butyric, lactic, and succinic acids can play significant roles. Most of the acids involved with wine are fixed acids with the notable exception of acetic acid, mostly found in vinegar, which is volatile and can contribute to the wine fault known as volatile acidity. Sometimes, additional acids, such as ascorbic, sorbic and sulfurous acids, are used in winemaking.

<span class="mw-page-title-main">Monomethyl fumarate</span> Chemical compound

Monomethyl fumarate, sold under the brand name Bafiertam is a medication used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is taken by mouth.

α,β-Unsaturated carbonyl compound Functional group of organic compounds

α,β-Unsaturated carbonyl compounds are organic compounds with the general structure (O=CR)−Cα=Cβ−R. Such compounds include enones and enals, but also carboxylic acids and the corresponding esters and amides. In these compounds, the carbonyl group is conjugated with an alkene. Unlike the case for carbonyls without a flanking alkene group, α,β-unsaturated carbonyl compounds are susceptible to attack by nucleophiles at the β-carbon. This pattern of reactivity is called vinylogous. Examples of unsaturated carbonyls are acrolein (propenal), mesityl oxide, acrylic acid, and maleic acid. Unsaturated carbonyls can be prepared in the laboratory in an aldol reaction and in the Perkin reaction.

<span class="mw-page-title-main">Diroximel fumarate</span> Medication

Diroximel fumarate, sold under the brand name Vumerity, is a medication used for the treatment of relapsing forms of multiple sclerosis (MS). It acts as an immunosuppressant and anti-inflammatory drug. Its most common adverse effects are flushing and gastrointestinal problems.

References

  1. Pubchem. "Fumaric acid". pubchem.ncbi.nlm.nih.gov.
  2. Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health
  3. 1 2 3 Lohbeck, Kurt; Haferkorn, Herbert; Fuhrmann, Werner; Fedtke, Norbert (2000). "Maleic and Fumaric Acids". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a16_053. ISBN   3-527-30673-0.
  4. Active Ingredients Used in Cosmetics: Safety Survey, Council of Europe. Committee of Experts on Cosmetic Products
  5. "Fumaric Acid Foods". Archived from the original on October 4, 2014. Retrieved 2018-04-22.
  6. UK Food Standards Agency: "Current EU approved additives and their E Numbers" . Retrieved 2011-10-27.
  7. US Food and Drug Administration: "Listing of Food Additives Status Part II". Food and Drug Administration . Retrieved 2011-10-27.
  8. Australia New Zealand Food Standards Code "Standard 1.2.4 - Labelling of ingredients". 8 September 2011. Retrieved 2011-10-27.
  9. "Fumaric Acid - The Chemical Company". The Chemical Company. Retrieved 2018-04-22.
  10. Eats, Serious. "The Science Behind Salt and Vinegar Chips". www.seriouseats.com.
  11. European Commission: "European Commission Report of the Scientific Committee on Animal Nutrition on the Safety of Fumaric Acid" (PDF). Retrieved 2014-03-07.
  12. 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 (12): 1098–1107. doi: 10.1056/NEJMoa1114287 . PMID   22992073. S2CID   6614191.
  13. Thompson, T. J.; Edee, R. Herbert (1925). "PREPARATION OF 6-METHYLCOUMARIN AND ITS DERIVATIVES". Journal of the American Chemical Society. 47 (10): 2556–2559. doi:10.1021/ja01687a019. ISSN   0002-7863.
  14. "Scientists look to cut cow flatulence". phys.org. March 21, 2008.
  15. Volhard, J. "Darstellung von Maleïnsäureanhydrid" Justus Liebig's Annalen der Chemie 1892, volume 268, page 255-6. doi : 10.1002/jlac.18922680108
  16. Nicholas A. Milas (1931). "Fumaric Acid". Organic Syntheses. 11: 46. doi:10.15227/orgsyn.011.0046.
  17. Herbert S. Rhinesmith (1938). "α,β-Dibromosuccinic Acid". Organic Syntheses. 18: 17. doi:10.15227/orgsyn.018.0017.