Fumaric acid

Fumaric acid


IUPAC name (E)-Butenedioic acid
Other names trans-1,2-Ethylenedicarboxylic acid 2-Butenedioic acid trans-butenedioic acid Allomaleic acid Boletic acid Donitic acid Lichenic acid
Identifiers
CAS number	110-17-8^Y
ChemSpider	10197150^Y
UNII	88XHZ13131^Y
EC number	203-743-0
DrugBank	DB04299
KEGG	C00122^Y
ChEBI	CHEBI:18012^Y
ChEMBL	CHEMBL503160^Y
Jmol-3D images	Image 1
SMILES C(=C/C(=O)O)\C(=O)O
InChI InChI=1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+^Y Key: VZCYOOQTPOCHFL-OWOJBTEDSA-N^Y InChI=1/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1+ Key: VZCYOOQTPOCHFL-OWOJBTEDBF
Properties
Molecular formula	C₄H₄O₄
Molar mass	116.07 g/mol
Appearance	White solid
Density	1.635 g/cm³, solid
Melting point	287 °C
Solubility in water	0.63 g/100 mL
Acidity (pK_a)	pk_a1 = 3.03, pk_a2 = 4.44
Hazards
EU classification	Irritant (Xi)
R-phrases	R36
S-phrases	(S2) S26
NFPA 704	1 2 0
Related compounds
Related carboxylic acids	maleic acid succinic acid crotonic acid
Related compounds	fumaryl chloride fumaronitrile dimethyl fumarate iron(II) fumarate
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Fumaric acid or trans-butenedioic acid is the chemical compound with the formula HO₂CCH=CHCO₂H. This white crystalline compound is one of two isomeric 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 has a fruit-like taste. The salts and esters are known as fumarates.

1 Biology
2 Medicine
3 Food
4 Chemistry
5 Other uses
6 Safety
7 Interactive pathway map
8 See also
9 References
10 External links

Biology

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.

Fumarate is also a product of the urea cycle.

Medicine

A fumaric acid ester is currently under investigation for treatment of multiple sclerosis.^[1]

Food

As a food additive, it is used as an acidity regulator and is denoted by the E number E297. Fumaric acid is a food acidulent used since 1946. It is non-toxic. It is generally used in beverages and baking powders for which requirements are placed on purity. It is generally used as a substitute for tartaric acid and occasionally in place of citric acid, at a rate of 1.36 g of citric acid to every 0.91 grams of fumaric acid to add sourness, similar to the way malic acid is used. It is also used as a coagulant in stovetop pudding mixes.

It is approved for use as a food additive in the EU^[2], USA^[3] and Australia and New Zealand^[4] (where it is listed by its INS number 297).

Chemistry

Fumaric acid was first prepared from succinic acid.^[5] A traditional synthesis involves oxidation of furfural (from the processing of maize) using chlorate in the presence of a vanadium-based catalyst.^[6] Currently, industrial synthesis of fumaric acid is mostly based on catalytic isomerisation of maleic acid in aqueous solutions at low pH. Maleic acid is accessible in large volumes as a hydrolysis product of maleic anhydride, produced by catalytic oxidation of benzene or butane.^[7]

The chemical properties of fumaric acid can be anticipated from its component functional groups. This weak acid forms a diester, it undergoes additions across the double bond, and it is an excellent dienophile.

Fumaric acid does not combust in a bomb calorimeter 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.

Other uses

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

Safety

Fumaric acid converts to the irritant maleic anhydride, upon partial combustion.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^[8]

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Citric_acid_cycle edit

References

^ Moharregh-Khiabani, D.; Linker, R.; Gold, R.; Stangel, M. (2009). "Fumaric Acid and its esters: an emerging treatment for multiple sclerosis". Current neuropharmacology 7 (1): 60–64. doi:10.2174/157015909787602788. PMC 2724664. PMID 19721818. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2724664. edit
^ UK Food Standards Agency: "Current EU approved additives and their E Numbers". http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist. Retrieved 2011-10-27.
^ US Food and Drug Administration: "Listing of Food Additives Status Part II". http://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT. Retrieved 2011-10-27.
^ Australia New Zealand Food Standards Code"Standard 1.2.4 - Labelling of ingredients". http://www.comlaw.gov.au/Details/F2011C00827. Retrieved 2011-10-27.
^ Volhard, J. "Darstellung von Maleïnsäureanhydrid" Justus Liebig's Annalen der Chemie 1892, volume 268, page 255-6. DOI: 10.1002/jlac.18922680108
^ Milas, N. A. "Fumaric Acid" Organic Synthesis 1943, Collective Volume 2, page 302. Online version
^ British Patent No. 775,912, publicated on the May 29, 1957, by Monsanto Chemical Company.
^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". http://www.wikipathways.org/index.php/Pathway:WP78.

External links

International Chemical Safety Card 1173

Fumarate

NADH + H⁺

NAD⁺

H₂O

FADH₂

FAD

CoA + ATP(GTP)

P_i + ADP(GDP)

H₂O

NADH + H⁺ + CO₂

CoA

NAD⁺

H₂O

NAD(P)⁺

NAD(P)H + H⁺

CO₂

cis-Aconitate

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

			L-citrulline		Carbamoyl phosphate	L-ornithine
				P_i

L-aspartate							Urea
	+	ATP
PP_i	+	AMP					H₂O



			L-argininosuccinate		Fumarate	L-arginine

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Antipsoriatics (D05)

Topical

Tars	Tar / Coal tar^#

Antracens	Dithranol^#

Psoralens	Trioxysalen • Methoxsalen

Other	Fumaric acid • vitamin D (Calcipotriol, Calcipotriol/betamethasone, Calcitriol, Tacalcitol) • Tazarotene

Systemic

Psoralens	Trioxysalen • Methoxsalen • Bergapten

Retinoids	Etretinate • Acitretin

^#WHO-EM. ^‡Withdrawn from market. Clinical trials: ^†Phase III. ^§Never to phase III

M: INT, SF, LCT

anat/phys/devp

noco(i/b/d/q/u/r/p/m/k/v/f)/cong/tumr(n/e/d), sysi/epon

proc, drug (D2/3/4/5/8/11)

Amino acid metabolism metabolic intermediates

K→acetyl-CoA

lysine→	Saccharopine · Allysine · α-Aminoadipic acid · α-Aminoadipate · Glutaryl-CoA · Glutaconyl-CoA · Crotonyl-CoA · β-Hydroxybutyryl-CoA

leucine→	α-Ketoisocaproic acid · Isovaleryl-CoA · 3-Methylcrotonyl-CoA · 3-Methylglutaconyl-CoA · HMG-CoA

tryptophan→alanine→	N'-Formylkynurenine · Kynurenine · Anthranilic acid · 3-Hydroxykynurenine · 3-Hydroxyanthranilic acid · 2-Amino-3-carboxymuconic semialdehyde · 2-Aminomuconic semialdehyde · 2-Aminomuconic acid · Glutaryl-CoA

G→pyruvate→citrate

glycine→serine→	3-Phosphoglyceric acid glycine→creatine: Glycocyamine · Phosphocreatine · Creatinine

G→glutamate→
α-ketoglutarate

histidine→	Urocanic acid · Imidazol-4-one-5-propionic acid · Formiminoglutamic acid · Glutamate-1-semialdehyde

proline→	1-Pyrroline-5-carboxylic acid

arginine→	Ornithine · Putrescine · Agmatine

other	cysteine+glutamate→glutathione: γ-Glutamylcysteine

G→propionyl-CoA→
succinyl-CoA

valine→	α-Ketoisovaleric acid · Isobutyryl-CoA · Methacrylyl-CoA · 3-Hydroxyisobutyryl-CoA · 3-Hydroxyisobutyric acid · 2-Methyl-3-oxopropanoic acid

isoleucine→	2,3-Dihydroxy-3-methylpentanoic acid · 2-Methylbutyryl-CoA · Tiglyl-CoA · 2-Methylacetoacetyl-CoA

methionine→	generation of homocysteine: S-Adenosyl methionine · S-Adenosyl-L-homocysteine · Homocysteine conversion to cysteine: Cystathionine · alpha-Ketobutyric acid+Cysteine

threonine→	α-Ketobutyric acid

propionyl-CoA→	Methylmalonyl-CoA

G→fumarate


phenylalanine→tyrosine→	4-Hydroxyphenylpyruvic acid · Homogentisic acid · 4-Maleylacetoacetate

G→oxaloacetate

see urea cycle

Other


Cysteine metabolism	Cysteine sulfinic acid

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

biochemical families: prot · nucl · carb (glpr, alco, glys) · lipd (fata/i, phld, strd, gllp, eico) · amac/i · ncbs/i · ttpy/i

Fumaric acid

Contents

Biology

Medicine

Food

Chemistry

Other uses

Safety

Interactive pathway map

See also

References

External links