Fumaric acid or ''trans''-butenedioic acid is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

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 (angiosperms) that is formed from the ovary after flowering. Fruits are the means by which angiosperms disseminate their seeds. Edible fruits in particular have long propaga ...

-like

taste The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste. Taste is the perception stimulated when a substance in the mouth biochemistry, reacts chemically with taste receptor cells l ...

and has been used as a

food additive Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives, such as vinegar ( pickling), salt ( salting), smoke ( smoking) and sugar ( crystallization), have been used f ...

. Its

E number E numbers, short for Europe numbers, 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 acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s are known as fumarates. Fumarate can also refer to the ion (in solution). Fumaric acid is the ''trans''

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

of butenedioic acid, while

maleic 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'' Cis–trans isomerism, isomer of butenedioic acid, ...

is the ''cis'' isomer.

Biosynthesis and occurrence

It is produced in

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

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

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

succinate dehydrogenase. Fumaric acid is found in fumitory (''Fumaria officinalis''), bolete

mushroom A mushroom or toadstool is the fleshy, spore-bearing Sporocarp (fungi), fruiting body of a fungus, typically produced above ground on soil or another food source. ''Toadstool'' generally refers to a poisonous mushroom. The standard for the n ...

s (specifically ''Boletus fomentarius var. pseudo-igniarius''),

lichen A lichen ( , ) is a hybrid colony (biology), colony of algae or cyanobacteria living symbiotically among hypha, filaments of multiple fungus species, along with yeasts and bacteria embedded in the cortex or "skin", in a mutualism (biology), m ...

, and Iceland moss. Fumarate is an intermediate in the

citric acid cycle The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

used by cells to produce energy in the form of

adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

(ATP) from

food Food is any substance consumed by an organism for Nutrient, nutritional support. Food is usually of plant, animal, or Fungus, fungal origin and contains essential nutrients such as carbohydrates, fats, protein (nutrient), proteins, vitamins, ...

. It is formed by the

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

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 Sunlight is the portion of the electromagnetic radiation which is emitted by the Sun (i.e. solar radiation) and received by the Earth, in particular the visible spectrum, visible light perceptible to the human eye as well as invisible infrare ...

. Fumarate is also a product of the urea cycle.

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

, it is used as an acidity regulator 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, 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.European Commission:

Medicine

Fumaric acid was developed as a medicine to treat the autoimmune condition psoriasis in the 1950s in Germany as a tablet containing 3

s, 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 Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

. 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

resin A resin is a solid or highly viscous liquid that can be converted into a polymer. Resins may be biological or synthetic in origin, but are typically harvested from plants. Resins are mixtures of organic compounds, predominantly terpenes. Commo ...

s and polyhydric alcohols and as a mordant for dyes. Fumaric acid can be used to make 6-methylcoumarin. When fumaric acid is added to their feed, lambs produce up to 70% less methane during digestion.

Synthesis

Fumaric acid is produced based on

catalytic Catalysis () is the increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...

isomerisation of

in aqueous solutions at low p''H''. 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 Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

or butane.

Historic and laboratory routes

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

maize Maize (; ''Zea mays''), also known as corn in North American English, is a tall stout grass that produces cereal grain. It was domesticated by indigenous peoples in southern Mexico about 9,000 years ago from wild teosinte. Native American ...

) using chlorate in the presence of a vanadium-based catalyst.

Reactions

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

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

s. This weak acid forms a di

, it undergoes bromination across the double bond, and it is a good dienophile.

Safety

The oral LD50 is 10g/kg.

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 Metabolic intermediates Biomolecules Carboxylic acid-based monomers