E363 – SUCCINIC ACID

E363 Succinic acid is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2.
In living organisms, E363 Succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state.
E363 Succinic acid is generated in mitochondria via the tricarboxylic acid (TCA) cycle. 

CAS:    110-15-6
MF:    C4H6O4
MW:    118.09
EINECS:    203-740-4

Synonyms
Succinic acid, 99% 250GR;Succinic acid, 99% 500GR;Succinic acid ACS;SUCCINIC ACID 99+% FCC;SUCCINIC ACID EXTRA PURE;SUCCINIC ACID, 99+%;SUCCINIC ACID, MATRIX SUBSTANCE FOR MALD I-MS;SUCCINIC ACID, PGE. WITH 10 X 10 MG

E363 Succinic acid can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling.
As such, E363 Succinic acid links cellular metabolism, especially ATP formation, to the regulation of cellular function.
Dysregulation of E363 Succinic acid synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh syndrome, and Melas syndrome, and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury.
E363 Succinic acid is marketed as food additive E363. 
The name derives from Latin E363 Succinic acid, meaning amber.
E363 Succinic acid is a dicarboxylic acid. 
E363 Succinic acid is a common intermediate in the metabolic pathway of several anaerobic and facultative micro-organisms.
E363 Succinic acid is used as a dietary supplement for symptoms related to menopause such as hot flashes and irritability. 

E363 Succinic acid is used as a flavoring agent for food and beverages. 
E363 Succinic acid is used to manufacture polyurethanes, paints and coatings, adhesives, sealants, artificial leathers, cosmetics and personal care products, biodegradable plastics, nylons, industrial lubricants, phthalate-free plasticizers, and dyes & pigments. 
In the pharmaceutical industry, E363 Succinic acid is used in the preparation of active calcium succinate, as a starting material for active pharmaceutical ingredients (adipic acid, N-methyl pyrrolidinone, 2-pyrrolidinone, succinate salts, etc.), as an additive in drug formation, for medicines of sedative, antispasmer, antiplegm, antiphogistic, anrhoter, contraception and cancer curing, in the preparation of vitamin A and anti-Inflammatory, and as antidote for toxic substance.
E363 Succinic acid is a dicarboxylic acid with a pair of carboxylic acid functional groups. 
The terminal carboxylic acid groups can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond.
An alpha,omega-dicarboxylic acid resulting from the formal oxidation of each of the terminal methyl groups of butane to the corresponding carboxy group. 
E363 Succinic acid is an intermediate metabolite in the citric acid cycle.
A crystalline carboxylic acid, HOOC(CH2)2COOH, that occurs in amber and certain plants. 
E363 Succinic acid forms during the fermentation of sugar (sucrose).

E363 Succinic acid Chemical Properties
Melting point: 185 °C
Boiling point: 235 °C
density: 1.19 g/mL at 25 °C(lit.)
bulk density: 940kg/m3
vapor pressure: 0-0Pa at 25℃
refractive index: n20/D 1.4002(lit.)
FEMA: 4719 | SUCCINIC ACID
Fp: >230 °F
storage temp.: 2-8°C
solubility: Soluble in ethanol, ethyl ether, acetone and methanol. Insoluble in toluene, benzene, carbon disulfide, carbon tetrachloride and petroleum ether.
pka: 4.16(at 25℃)
form: Powder/Solid
color: White to off-white
PH: 3.65(1 mM solution);3.12(10 mM solution);2.61(100 mM solution);
Odor: at 100.00 %. wormwood
Odor Type: herbal
biological source: synthetic
Water Solubility: 80 g/L (20 ºC)
Merck: 14,8869
JECFA Number: 2307
BRN: 1754069
Henry's Law Constant: 3.1×107 mol/(m3Pa) at 25℃, Burkholder et al. (2019)
Dielectric constant: 2.4（26℃）
Stability: Stable. Substances to be avoided include strong bases, strong oxidizing agents. Combustible.
Cosmetics Ingredients Functions: FRAGRANCE
BUFFERING
InChI: 1S/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8)
InChIKey: KDYFGRWQOYBRFD-UHFFFAOYSA-N
LogP: -0.59
CAS DataBase Reference: 110-15-6(CAS DataBase Reference)
NIST Chemistry Reference: E363 Succinic acid (110-15-6)
EPA Substance Registry System: E363 Succinic acid (110-15-6)

E363 Succinic acid is a normal constituent of almost all plant and animal tissues. 
E363 Succinic acid is the dehydration product of the acid. 
E363 Succinic acid was first obtained as the distillate from amber (Latin, Succinum) for which it is named. 
E363 Succinic acid occurs in beet, brocoli, rhubarb, sauerkraut, cheese, meat, molasses, eggs, peat, coal, fruits, honey, and urine (Gardner, 1972; Winstrom, 1978; Doores, 1989). 
E363 Succinic acid is formed by the chemical and biochemical oxidation of fats, by alcoholic fermentation of sugar, and in numerous catalyzed oxidation processes. 
E363 Succinic acid is also a major byproduct in the manufacture of adipic acid.
E363 Succinic acid, a dicarboxylic acid, is a relatively new nonhygroscopic product approved for food uses. 
E363 Succinic acid's apparent taste characteristics in foods appear to be very similar to the other acidulants of this type, although pure aqueous solutions tend to have a slightly bitter taste.
E363 Succinic acid,C02H(CH2)2C02H, also known as butanedioic acid,butane diacid, and amber acid, is a colorless odorless prisms or white crystalline powder that melts at 185°C (364 of). 
Soluble in water and alcohol, E363 Succinic acid is used as a chemical intermediate, Succinic acid is used in lacquers,medicine,dyes,and as a taste modifier.

Physical properties
E363 Succinic acid is a white, odorless solid with a highly acidic taste.
In an aqueous solution, succinic acid readily ionizes to form its conjugate base, succinate. 
As a diprotic acid, E363 Succinic acid undergoes two successive deprotonation reactions:

(CH2)2(CO2H)2 → (CH2)2(CO2H)(CO2)− + H+
(CH2)2(CO2H)(CO2)− → (CH2)2(CO2)22− + H+
The pKa of these processes are 4.3 and 5.6, respectively. 
Both anions are colorless and can be isolated as the salts, e.g., Na(CH2)2(CO2H)(CO2) and Na2(CH2)2(CO2)2. 
In living organisms, primarily succinate, not E363 Succinic acid, is found.
As a radical group E363 Succinic acid is called a succinyl group.
Like most simple mono- and dicarboxylic acids, E363 Succinic acid is not harmful but can be an irritant to skin and eyes.

Chemical reactions
E363 Succinic acid can be dehydrogenated to fumaric acid or be converted to diesters, such as diethylsuccinate (CH2CO2CH2CH3)2. 
This diethyl ester is a substrate in the Stobbe condensation. 
Dehydration of E363 Succinic acid gives succinic anhydride.
E363 Succinic acid can be used to derive 1,4-butanediol, maleic anhydride, succinimide, 2-pyrrolidinone and tetrahydrofuran.

Uses    
E363 Succinic acid is a carboxylic acid used in food (as an acidulant), pharmaceutical (as an excipient), personal care (soaps) and chemical (pesticides, dyes and lacquers) industries. 
Bio-based E363 Succinic acid is seen as an important platform chemical for the production of biodegradable plastics and as a substitute of several chemicals (such as adipic acid).
E363 Succinic acid is widely used in the food industry as a chelating agent and as a pH adjuster. 
The FDA has granted E363 Succinic acid with the GRAS status. 
Studies conducted within the food industry show E363 Succinic acid has anti-oxidant properties: even though this does not imply the same will be exerted when the substance is applied topically, it gives an indication that suitable tests could be carried out to understand whether E363 Succinic acid maintain such effect once formulated in a cosmetic product. 

E363 Succinic acid is also used as an intermediate to manufacture several chemicals, amongst which raw materials for the cosmetic and personal-care industry, e.g. emollients, surfactants and emulsifiers.
E363 Succinic acid was identified in essential oil from Saxifraga stolonifera and has antibacterial activity.
E363 Succinic acid is an acidulant that is commercially prepared by the hydrogenation of maleic or fumaric acid. 
E363 Succinic acid is a nonhygroscopic acid but is more soluble in 25°c water than fumaric and adipic acid. 
E363 Succinic acid has low acid strength and slow taste build-up; it is not a substitute for normal acidulants. 
E363 Succinic acid combines with proteins in modifying the plasticity of bread dough. 
E363 Succinic acid functions as an acidulant and flavor enhancer in relishes, beverages, and hot sausages.

Biotechnological Applications    
E363 Succinic acid and its derivatives are used as flavoring agents for food and beverages. 
E363 Succinic acid could be used as feedstock for dyes, insecticides, perfumes, lacquers, as well as in the manufacture of clothing, paint, links, and fibers. 
E363 Succinic acid is widely used in medicine as an antistress, antihypoxic, and immunity-improving agent, in animal diets, and as a stimulator of plant growth. 
E363 Succinic acid is also a component of bio-based polymers such as nylons or polyesters. 
Succinate esters are precursors for the known petrochemical products such as 1,4-butanediol, tetrahydrofuran, c-butyrolactone, and various pyrrolidinone derivatives.
E363 Succinic acid production by Y. lipolytica was reported for the first time when it was grown on ethanol under aerobic conditions and nitrogen limitation. 
E363 Succinic acid amount was 63.4 g/L as the major product of batch fermentation in this process. 
However, the disadvantage was low yield of E363 Succinic acid on ethanol (58 %), and a high cost of production.

Kamzolova et al. developed a novel process for the production of E363 Succinic acid. 
E363 Succinic acid includes the synthesis of a-ketoglutaric acid by a thiamine-auxotrophic strain Y. lipolytica VKMY-2412 from n-alkanes, and subsequent oxidation of the acid by hydrogen peroxide to succinic acid. 
The concentration of succinic acid and its yield were found to be 38.8 g/L and 82.45 % of n-alkane consumed, respectively (Kamzolova et al. 2012b).
E363 Succinic acid production was also studied by genetically modified strains using glucose and glycerol as substrates. 
Yuzbashev et al. constructed temperaturesensitive mutant strains with mutations in the succinate dehydrogenase encoding gene SDH1 by in vitro mutagenesis-based approach. 
Then, the mutants were used to optimize the composition of the media for selection of transformants with the deletion in the SDH2 gene. 
The defects of each succinate dehydrogenase subunit prevented the growth on glucose, but the mutant strains grew on glycerol and produced succinate in the presence of the buffering agent CaCO3. 
Subsequent selection of the strain with deleted SDH2 gene for increased viability was allowed to obtain a strain that is capable to accumulate succinate at the level of more than 450 g/L with buffering and more than 17 g/L without buffering. 
Therefore, a reduced succinate dehydrogenase activity can lead to an increased succinate production (Yuzbashev et al. 2010). Y. lipolytica is able to produce succinic acid at low pH values. 
High amounts of E363 Succinic acid can be achieved by genetic engineering.

Preparation    
E363 Succinic acid can also be manufactured by catalytic hydrogenation of malic or fumaric acids. 
E363 Succinic acid has also been produced commercially by aqueous acid or alkalihydrolysis of succinonitrile derived from ethylene bromide and potassium cyanide.
Today E363 Succinic acid is mainly produced from fossil resources through maleic acid hydrogenation. 
E363 Succinic acid can also be produced through fermentation of sugars. 
In that case, in addition to E363 Succinic acid, other carboxylic acids (such as lactic acid, formic acid, propionic acid) and alcohols (such as ethanol) are also obtained.

Toxicology    
E363 Succinic acid is moderately toxic by subcutaneous route. 
E363 Succinic acid is also a severe eye irritant. 
When heated to decomposition, E363 Succinic acid emits acrid smoke and irritating fumes.
Dye et al. (1944) conducted short-term studies on rats who received daily subcutaneous injections of 0.5 mg E363 Succinic acid. 
These doses were increased gradually up to 2.0 mg/day at 4 weeks, and the studies continued at this level for 100 days. 
When compared with the control animals, the test animals did not show any abnormalities in reproduction, hair appearance, tooth eruption, or eye opening.
Dye et al. (1944) also found no abnormalities in the development of chick embryos when comparable dosages were administered into the air sacs.
Since E363 Succinic acid occurs naturally in small amounts in several fruits and vegetables and as an intermediate in the Krebs cycle, no limit has been set on the acceptable daily intake of succinic acid in the human diet.

Biochem/physiol Actions    
E363 Succinic acid is a byproduct of anaerobic fermentation in microbes. 
E363 Succinic acid is a dicarboxylic acid and an intermediate in Kreb′s cycle. 
Polymorphism in succinate dehydrogenase leads to succinate accumulation. 
High levels of succinate impairs 2-oxoglutarate epigenetic signalling.
E363 Succinic acid levels may modulate tumor progression. 
Succinate inhibits histone demethylation and may contribute to epigenetic changes. 
E363 Succinic acid is crucial for interleukin-1 β (IL-1β) synthesis during inflammation and immune signalling.