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. The ...

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 particu ...

-like

taste The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...

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 In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...

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 ar ...

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 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 ac ...

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 Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

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. A ...

succinate dehydrogenase. 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. Is ...

unsaturated dicarboxylic acids, the other being

. 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'' (fumitory or fumewort, from Latin ', "smoke of the earth") is a genus of about 60 species of annual flowering plants in the family Papaveraceae. The genus is native to Europe, Africa and Asia, most diverse in the Mediterranean re ...

(''Fumaria officinalis''),

bolete {{refimprove, date=July 2020 A bolete is a type of mushroom, or fungal fruiting body. It can be identified thanks to a unique mushroom cap. The cap is clearly different from the stem. On the underside of the cap there is usually a spongy surf ...

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 t ...

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

Iceland moss ''Cetraria islandica'', also known as true Iceland lichen or Iceland moss, is an Arctic-alpine lichen whose erect or upright, leaflike habit gives it the appearance of a moss, where its name likely comes from. Description It is often of a pale ...

. 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 protein ...

used by cells 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 o ...

(ATP) from

food Food is any substance consumed by an organism for nutritional support. Food is usually of plant, animal, or fungal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is inge ...

. 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 a d ...

by the enzyme succinate dehydrogenase. Fumarate is then converted by the enzyme

fumarase Fumarase (or fumarate hydratase) is an enzyme () that catalyzes the reversible hydration/dehydration of fumarate to malate. Fumarase comes in two forms: mitochondrial and cytosolic. The mitochondrial isoenzyme is involved in the Krebs cycle and ...

malate Malic acid is an organic compound with the molecular formula . 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 (L ...

. 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 t ...

. Fumarate is also a product of the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of Biochemistry, 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 ...

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 and can be denoted by the

E297. It is generally used in beverages and

baking powder Baking powder is a dry chemical leavening agent, a mixture of a carbonate or bicarbonate and a weak acid. The base and acid are prevented from reacting prematurely by the inclusion of a buffer such as cornstarch. Baking powder is used to increas ...

s for which requirements are placed on purity. Fumaric acid is used in the making of

wheat tortilla A flour tortilla (, ) or wheat tortilla is a type of soft, thin flatbread made from finely ground wheat flour. It was originally inspired by the corn tortilla of Mexican cuisine, a flatbread of maize which predates the arrival of Europeans to ...

s as a food preservative and as the acid in leavening. It is generally used as a substitute for

tartaric acid Tartaric acid is a white, crystalline organic acid that occurs naturally in many fruits, most notably in grapes, but also in bananas, tamarinds, and citrus. Its salt, potassium bitartrate, commonly known as cream of tartar, develops naturally ...

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 The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste recepto ...

, similarly to the way

malic acid Malic acid is an organic compound with the molecular formula . 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 ( ...

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 DG may refer to: Arts and entertainment * Death Grips, an American experimental hip hop group * DG (character), in the science fiction series ''Tin Man'' * Dial Global, a radio network * Dragon Gate (wrestling), Dragon Gate, a Japanese profession ...

, found in 2014 that fumaric acid is "practically non-toxic" but high doses are probably

nephrotoxic Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins ...

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 complete ...

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 thera ...

, and marketed as Fumaderm by

Biogen Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide. History ...

Idec in Europe. Biogen would later go on to develop the main ester, dimethyl fumarate, as a treatment for

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

. 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 Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the ''NFE2L2'' gene. NRF2 is a basic leucine zipper (bZIP) protein that may reg ...

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 natural ...

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 natu ...

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 soli ...

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

after long-term use.European Commission:

Synthesis and reactions

Fumaric acid was first prepared from

succinic acid Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

. 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 and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. Th ...

) using chlorate in the presence of a

vanadium Vanadium is a chemical element with the symbol V and atomic number 23. It is a hard, silvery-grey, malleable transition metal. The elemental metal is rarely found in nature, but once isolated artificially, the formation of an oxide layer ( pas ...

-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 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 ...

isomerisation of

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 reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

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, ...

or butane. 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 re ...

s. This weak acid forms a di

, it undergoes additions across the

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...

, and it is an excellent dienophile. Fumaric acid does not combust in a bomb calorimeter under conditions where

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