Fumaric acid

Names
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 Registry Number	110-17-8 Y
ATC code	D05AX01
ChEBI	CHEBI:18012 Y
ChEMBL	ChEMBL503160 Y
ChemSpider	10197150 Y
DrugBank	DB04299 Y
EC number	203-743-0
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
Jmol-3D images	Image
KEGG	C00122 Y
SMILES C(=C/C(=O)O)\C(=O)O
UNII	88XHZ13131 Y
Properties
Chemical formula	C4H4O4
Molar mass	116.07 g·mol−1
Appearance	White solid
Density	1.635 g/cm3
Melting point	287 °C (549 °F; 560 K) (decomp)[2]
Solubility in water	4.3 g/L at 20°C[1]
Acidity (pKa)	pka1 = 3.03, pka2 = 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
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is: Y/N?)
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.

Chemistry[edit]

Fumaric acid was first prepared from succinic acid.^[3] A traditional synthesis involves oxidation of furfural (from the processing of maize) using chlorate in the presence of a vanadium-based catalyst.^[4] 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.^[5]

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.

Biology[edit]

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.^[6]

Fumarate is also a product of the urea cycle.

Uses[edit]

Food[edit]

Fumaric acid has been used a food acidulant since 1946. It is approved for use as a food additive in the EU,^[7] USA^[8] and Australia and New Zealand.^[9] As a food additive, it is used as an acidity regulator and can be denoted by the E number E297. 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 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,^[10] it is also used as a coagulant in stovetop pudding mixes.

Medicine[edit]

In patients with relapsing-remitting multiple sclerosis, 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.^[11]

Other uses[edit]

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

Safety[edit]

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

It is "practically non-toxic" but high doses are probably nephrotoxic after long term use.^[12]

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|{{{bSize}}}px|alt=TCA Cycle edit]]

File:TCACycle WP78.png

TCA Cycle edit

1. ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". 

See also[edit]

• Dermatology
• Photosynthesis
• Maleic acid, the cis-isomer of fumaric acid

References[edit]

1. ^ Record in the GESTIS Substance Database of the IFA
2. ^ Fumaric acid, PubChem
3. ^ Volhard, J. "Darstellung von Maleïnsäureanhydrid" Justus Liebig's Annalen der Chemie 1892, volume 268, page 255-6. doi:10.1002/jlac.18922680108
4. ^ Milas, N. A. "Fumaric Acid" Organic Synthesis 1943, Collective Volume 2, page 302. Online version
5. ^ British Patent No. 775,912, publicated on the May 29, 1957, by Monsanto Chemical Company.
6. ^ Active Ingredients Used in Cosmetics: Safety Survey, Council of Europe. Committee of Experts on Cosmetic Products
7. ^ UK Food Standards Agency: "Current EU approved additives and their E Numbers". Retrieved 2011-10-27. 
8. ^ US Food and Drug Administration: "Listing of Food Additives Status Part II". Retrieved 2011-10-27. 
9. ^ Australia New Zealand Food Standards Code"Standard 1.2.4 - Labelling of ingredients". Retrieved 2011-10-27. 
10. ^ http://www.seriouseats.com/2012/09/the-best-salt-and-vinegar-chips-tasting-brands-most-acidic.html
11. ^ Gold R., Kappos L., Arnold D.L.; et al. (September 20, 2012). "Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis". N Engl J Med 367 (12): 1098–1107. doi:10.1056/NEJMoa1114287. PMID 22992073. 
12. ^ European Commission: "European Commission Report of the Scientific Committee on Animal Nutrition on the Safety of Fumaric Acid" (PDF). Retrieved 2014-03-07. 

External links[edit]

• International Chemical Safety Card 1173

Citric acid cycle metabolic pathway
			Oxaloacetate			Malate			Fumarate			Succinate			Succinyl-CoA
Acetyl-CoA				NADH + H+	NAD+			H2O		FADH2	FAD		CoA + ATP(GTP)	Pi + ADP(GDP)
	+	H2O														NADH + H+ + CO2
		CoA														NAD+
					H2O		H2O			NAD(P)+	NAD(P)H + H+			CO2
			Citrate			cis-Aconitate			Isocitrate			Oxalosuccinate			α-Ketoglutarate
Index of inborn errors of metabolism Description Metabolism Enzymes and pathways: citric acid cycle enzymes pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes phospholipid metabolism cholesterol and steroid intermediates sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes nucleotide intermediates Disorders Citric acid cycle and electron transport chain Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs Treatment Drugs other

Urea cycle Metabolic Pathway
L-citrulline Carbamoyl phosphate L-ornithine Pi L-aspartate Urea + ATP PPi + AMP H2O L-argininosuccinate Fumarate L-arginine
Index of inborn errors of metabolism Description Metabolism Enzymes and pathways: citric acid cycle enzymes pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes phospholipid metabolism cholesterol and steroid intermediates sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes nucleotide intermediates Disorders Citric acid cycle and electron transport chain Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs Treatment Drugs other