Itaconic acid

Itaconic acid

Names
Preferred IUPAC name Methylidenebutanedioic acid
Other names 2-Methylenesuccinic acid Methylenesuccinic acid[1] 1-Propene-2,3-dicarboxylic acid
Identifiers
CAS Number	97-65-4 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:30838 Y
ChEMBL	ChEMBL359159 Y
ChemSpider	789 Y
ECHA InfoCard	100.002.364
KEGG	C00490 Y
PubChem CID	811
UNII	Q4516562YH Y
CompTox Dashboard (EPA)	DTXSID2026608
InChI InChI=1S/C5H6O4/c1-3(5(8)9)2-4(6)7/h1-2H2,(H,6,7)(H,8,9) Y Key: LVHBHZANLOWSRM-UHFFFAOYSA-N Y InChI=1/C5H6O4/c1-3(5(8)9)2-4(6)7/h1-2H2,(H,6,7)(H,8,9) Key: LVHBHZANLOWSRM-UHFFFAOYAS
SMILES O=C(O)C(=C)CC(=O)O
Properties
Chemical formula	C5H6O4
Molar mass	130.099 g·mol−1
Appearance	White solid
Density	1.63 g/cm3[1]
Melting point	162 to 164 °C (324 to 327 °F; 435 to 437 K) (decomposes)[1]
Solubility in water	1 g/12 mL[1]
Solubility in ethanol	1 g/5 mL[1]
Magnetic susceptibility (χ)	-57.57·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Itaconic acid (also termed methylidenesuccinic acid and 2-methylidenebutanedioic acid^[2]) is a fatty acid containing five carbons (carbon notated as C), two of which are in carboxyl groups (notated as -CO₂H) and two others which are double bonded together (i.e., C=C). (itaconic acid's chemical formula is C₅H₆O₄, see adjacent figure and dicarboxylic acids). At the strongly acidic pH levels below 2, itaconic acid is electrically neutral because both of its carboxy residues are bound to hydrogen (notated as H); at the basic pH levels above 7, it is double negatively charged because both of its carboxy residues are not bound to H, i.e., CO₂${\displaystyle ^{-}}$ (its chemical formula is C₅H₄O₄^2-); and at acidic pH's between 2 and 7, it exists as a mixture with none, one, or both of its carboxy residues bound to hydrogen. In the cells and most fluids of living animals, which generally have pH levels above 7, itaconic acid exists almost exclusively in its double negatively charged form; this form of itaconic acid is termed itaconate.^[3] Itaconic acid and itaconate exist as cis and trans isomers (see cis–trans isomerism). Cis-itaconic acid and cis-itaconate isomers have two H's bound to one carbon and two residues (noted as R) bound to the other carbon in the double bound (i.e., H₂C=CR₂) whereas trans-itaconic acid and trans-itaconate have one H and one R residue bound to each carbon of the double bound. The adjacent figure shows the cis form of itaconic acid. Cis-aconitic acid spontaneously converts to its thermodynamically more stable (see chemical stability) isomer, trans-aconitic acid, at pH levels below 7.^[4] The medical literature commonly uses the terms itaconic acid and itaconate without identifying them as their cis isomers. This practice is used here, i.e., itaconic acid and itaconate refer to their cis isomers while the trans isomer of itaconate (which has been detected in fungi but not animals^[4]) is here termed trans-itaconate (trans-itaconic acid is not further mentioned here).

Animal cells make itaconate by an enzyme-catalyzed reaction from cis-aconitate (see aconitic acid), an intermediate metabolite in the tricarboxylic acid cycle, (i.e., TCA cycle). This cycle operates in the mitochondria of virtually all the cells of animals, plants, fungi, and some microorganisms.^[5] The itaconate-producing reaction is stimulated when cells undergo stressful conditions that suppress the TCA cycle's operation.^[6] Studies examining the actions of itaconate and/or itaconate-like compounds suggest that the itaconate formed in this reaction acts on its cell of origin and other cells to regulate the potentially deleterious inflammation responses caused by various microorganisms, viruses, autoimmune diseases, oxidative stress, and other types of tissue injury.^[6] They also suggest that it may inhibit the development and/or progression of certain cancers.^[7] Itaconate is also a bactericidal agent, i.e., an agent that acts directly on certain types of bacteria to inhibit their viability and/or disease-causing abilities.^[8][9]

In 1836, Samuel Baup discovered a previously unknown by-product in a distillate of citric acid; this by-product was later named itaconic acid.^[6] In the late 1920s, itaconic acid was isolated from a fungus in the Aspergillus genus of fungi^[6] and in the 1930s itaconate was shown to have bactericidal actions.^[8][9] During this time, itaconic acid proved to be useful for synthesizing a wide range of products required by agricultural, textile, and other industries. Since then, the use of itaconic acid for industrial and manufacturing purposes has grown.^[10] In 2011, Strelko et al.^[11] reported that itaconate was produced by two mammalian immortalized cell lines, cultured mouse VM-M3 brain tumor cells and RAW 264.7 mouse macrophages, and by macrophages isolated from mice. This group also showed that stimulation of mouse macrophages with the bacterial toxin, lipopolysaccharide (i.e., LPS, also termed endotoxin), increased their production and secretion of itaconate.^[7] In 2013, Michelucci et al.^[12] revealed the biosynthesis pathway that makes itaconate in mammals. These publications were followed by numerous others focused on the biology of itaconate and certain itaconate-like compounds as regulars of various cellular responses in animals and possibly humans.^[7][13]

The following section, titled "Biology of Itaconate," details preclinical studies that analyzed the effects of itaconate and itaconate-like compounds on human cells, animal cells, and animals used as models of specific diseases. These studies sought to a) define itaconate's physiological and pathological functions as well as its mechanisms of action in health and disease; b) define the actions and mechanisms of action of various itaconate-like compounds; and c) determine which actions of itaconate and itaconate-like compounds support conducting further studies to determine if it or they would be useful therapeutic agents in humans.^[6][7][14] The last section, titled "Commercial production and uses of itaconic acid," reports on the changing methods for making large amounts, and the many commercial uses, of itaconic acid.^[3][15]