Fumaric 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 Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salt ...

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

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 i ...

. It is one of two isomeric unsaturated

dicarboxylic acid In organic chemistry, a dicarboxylic acid is an organic compound containing two carboxyl groups (). The general molecular formula for dicarboxylic acids can be written as , where R can be aliphatic or aromatic. In general, dicarboxylic acids show ...

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

lichen A lichen ( , ) is a composite organism that arises from algae or cyanobacteria living among filaments of multiple fungi species in a mutualistic relationship.Iceland moss. Fumarate is an intermediate in the citric acid cycle 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 (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 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 t ...

. 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 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, 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 Coagulant can refer to: * Flocculation * Coagulation of the blood * Coagulation (water treatment) See also * Coagulation (disambiguation) Coagulation is the process by which blood forms clots. Coagulation may also refer to: * Coagulation (water ...

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 in the 1950s in Germany as a tablet containing 3 esters, 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 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 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 ...

resins and polyhydric alcohols and as a mordant 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 Furfural is an organic compound with the formula C4H3OCHO. It is a colorless liquid, although commercial samples are often brown. It has an aldehyde group attached to the 2-position of furan. It is a product of the dehydration of sugars, as occurs ...

(from the processing of maize) using

chlorate The chlorate anion has the formula ClO3-. In this case, the chlorine atom is in the +5 oxidation state. "Chlorate" can also refer to chemical compounds containing this anion; chlorates are the salts of chloric acid. "Chlorate", when followed by ...

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.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 In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...

of maleic acid in aqueous solutions at low p''H''. Maleic acid is accessible in large volumes as a hydrolysis product of maleic anhydride, produced by catalytic oxidation of benzene or

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 groups. This weak acid forms a di ester, 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