Fumaric acid is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

with the formula HO₂CCH=CHCO₂H. A white solid, fumaric acid occurs widely in nature. It has a

fruit In botany, a fruit is the seed-bearing structure in flowering plants that is formed from the ovary after flowering. Fruits are the means by which flowering plants (also known as angiosperms) disseminate their seeds. Edible fruits in partic ...

-like taste and has been used as a food additive. Its

E number E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...

is E297. The salts and

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

s are known as fumarates. Fumarate can also refer to the ion (in solution). Fumaric acid is the trans isomer of butenedioic acid, while maleic acid is the cis isomer.

Biosynthesis and occurrence

It is produced in

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

organisms from succinate in complex 2 of the electron transport chain via the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

succinate dehydrogenase Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates ...

. It is one of two

isomeric In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...

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 is found in fumitory (''Fumaria officinalis''), bolete

mushroom A mushroom or toadstool is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground, on soil, or on its food source. ''Toadstool'' generally denotes one poisonous to humans. The standard for the name "mushroom" is ...

s (specifically ''Boletus fomentarius var. pseudo-igniarius''), lichen, and Iceland moss. Fumarate is an intermediate in the

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and prot ...

used by

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

to produce energy in the form of

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...

(ATP) from food. It is formed by the

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...

of succinate by the enzyme

. Fumarate is then converted by the enzyme fumarase to malate. Human skin naturally produces fumaric acid when exposed to

sunlight Sunlight is a portion of the electromagnetic radiation given off by the Sun, in particular infrared, visible, and ultraviolet light. On Earth, sunlight is scattered and filtered through Earth's atmosphere, and is obvious as daylight when ...

. Fumarate is also a product of the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts h ...

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, USA and Australia and New Zealand. As a food additive, it is used as an

acidity regulator Acidity regulators, or pH control agents, are food additives used to change or maintain pH (acidity or basicity). They can be organic or mineral acids, bases, neutralizing agents, or buffering agents. Typical agents include the following acids ...

and can be denoted by the

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. It is generally used as a substitute for tartaric acid and occasionally in place of

citric acid Citric acid is an organic compound with the chemical 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 ...

, 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, 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.

Medicine

Fumaric acid was developed as a medicine to treat the autoimmune condition

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to comple ...

in the 1950s in Germany as a tablet containing 3

s, primarily

dimethyl fumarate Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and is named after the earth smoke plant (''Fumaria officinalis''). Dimethyl fumarate combined with three other fumaric acid esters (FAEs) is solely licensed in Germany as an oral ther ...

, 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.

Other uses

Fumaric acid is used in the manufacture of

polyester Polyester is a category of polymers that contain the ester functional group in every repeat unit of their main chain. As a specific material, it most commonly refers to a type called polyethylene terephthalate (PET). Polyesters include natura ...

resin In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on nat ...

s and

polyhydric alcohol Sugar alcohols (also called polyhydric alcohols, polyalcohols, alditols or glycitols) are organic compounds, typically derived from sugars, containing one hydroxyl group (–OH) attached to each carbon atom. They are white, water-soluble solid ...

s and as a

mordant A mordant or dye fixative is a substance used to set (i.e. bind) dyes on fabrics by forming a coordination complex with the dye, which then attaches to the fabric (or tissue). It may be used for dyeing fabrics or for intensifying stains in ...

for dyes. When fumaric acid is added to their feed, lambs produce up to 70% less methane during digestion.

Safety

It is "practically non-toxic" but high doses are probably nephrotoxic after long-term use.European Commission:

Synthesis and reactions

Fumaric acid was first prepared from succinic acid. A traditional synthesis involves oxidation of furfural (from the processing of

maize Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American English, North American and Australian English), is a cereal grain first domesticated by indigenous peoples of Mexico, indigenous ...

) using chlorate in the presence of a vanadium-based

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

.Milas, N. A. "Fumaric Acid" ''Organic Synthesis'' 1943, Collective Volume 2, page 302
Online version
/ref> Currently, industrial synthesis of fumaric acid is mostly based on catalytic isomerisation of maleic acid in aqueous solutions at low p''H''. Maleic acid is accessible in large volumes as a

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...

product of maleic anhydride, produced by catalytic oxidation of

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...

butane Butane () or ''n''-butane is an alkane with the formula C4H10. Butane is a gas at room temperature and atmospheric pressure. Butane is a highly flammable, colorless, easily liquefied gas that quickly vaporizes at room temperature. The name but ...

. The chemical properties of fumaric acid can be anticipated from its component

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...

s. This weak acid forms a di

, it undergoes additions across the double bond, and it is an excellent dienophile. Fumaric acid does not combust in a

bomb calorimeter A bomb is an explosive weapon that uses the exothermic reaction of an explosive material to provide an extremely sudden and violent release of energy. Detonations inflict damage principally through ground- and atmosphere-transmitted mechanica ...

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.

References

External links

International Chemical Safety Card 1173
{{Authority control Dicarboxylic acids Food additives Food acidity regulators Urea cycle Citric acid cycle compounds Nephrotoxins E-number additives Alkene derivatives