Succinic acid
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| Names | |
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| Preferred IUPAC name
Butanedioic acid[1] | |
| Other names
Succinic acid[1]
1,4-Butanedioic acid | |
| Identifiers | |
3D model (
JSmol ) |
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| DrugBank | |
ECHA InfoCard
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100.003.402 |
| E number | E363 (antioxidants, ...) |
IUPHAR/BPS |
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PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C4H6O4 | |
| Molar mass | 118.088 g·mol−1 |
| Density | 1.56 g/cm3[2] |
| Melting point | 184–190 °C (363–374 °F; 457–463 K)[2][4] |
| Boiling point | 235 °C (455 °F; 508 K)[2] |
| 58 g/L (20 °C)[2] or 100 mg/mL[3] | |
| Solubility in Methanol | 158 mg/mL[3] |
| Solubility in Ethanol | 54 mg/mL[3] |
| Solubility in Acetone | 27 mg/mL[3] |
| Solubility in Glycerol | 50 mg/mL[3] |
| Solubility in Ether | 8.8 mg/mL[3] |
| Acidity (pKa) | pKa1 = 4.2 pKa2 = 5.6 |
| -57.9·10−6 cm3/mol | |
| Hazards | |
| Flash point | 206 °C (403 °F; 479 K)[2] |
| Related compounds | |
Other anions
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sodium succinate
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Related carboxylic acids
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propionic acid malonic acid butyric acid malic acid tartaric acid fumaric acid valeric acid glutaric acid |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Succinic acid (
Succinate is generated in
Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as
Succinic acid is marketed as food additive
Physical properties
Succinic acid is a white, odorless solid with a highly acidic taste.
- (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 succinic acid, is found.[5]
As a radical group it is called a succinyl (/ˈsʌksɪnəl/) group.[9]
Like most simple mono- and dicarboxylic acids, it is not harmful but can be an irritant to skin and eyes.[5]
Commercial production
Historically, succinic acid was obtained from
Genetically engineered Escherichia coli and Saccharomyces cerevisiae are proposed for the commercial production via fermentation of glucose.[12][13]
Chemical reactions
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 succinic acid gives succinic anhydride.[14] Succinate can be used to derive 1,4-butanediol, maleic anhydride, succinimide, 2-pyrrolidinone and tetrahydrofuran.[12]
Applications
In 2004, succinate was placed on the US Department of Energy's list of top 12 platform chemicals from biomass.[15]
Precursor to polymers, resins, and solvents
Succinic acid is a
Acylation with succinic acid is called succination. Oversuccination occurs when more than one succinate adds to a substrate.[citation needed]
Food and dietary supplement
As a
Biosynthesis
Tricarboxylic acid (TCA) cycle
Succinate is a key intermediate in the tricarboxylic acid cycle, a primary metabolic pathway used to produce chemical energy in the presence of O2. Succinate is generated from succinyl-CoA by the enzyme succinyl-CoA synthetase in a GTP/ATP-producing step:[22]: Section 17.1
Succinyl-CoA + NDP + Pi → Succinate + CoA + NTP
Catalyzed by the enzyme succinate dehydrogenase (SDH), succinate is subsequently oxidized to fumarate:[22]: Section 17.1
Succinate + FAD → Fumarate + FADH2
SDH also participates in the mitochondrial
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".
Reductive branch of the TCA cycle
Succinate can alternatively be formed by reverse activity of SDH. Under anaerobic conditions certain bacteria such as A. succinogenes, A. succiniciproducens and M. succiniciproducens, run the TCA cycle in reverse and convert glucose to succinate through the intermediates of oxaloacetate, malate and fumarate.[24] This pathway is exploited in metabolic engineering to net generate succinate for human use.[24] Additionally, succinic acid produced during the fermentation of sugar provides a combination of saltiness, bitterness and acidity to fermented alcohols.[25]
Accumulation of fumarate can drive the reverse activity of SDH, thus enhancing succinate generation. Under pathological and physiological conditions, the
Glyoxylate cycle
Succinate is also a product of the glyoxylate cycle, which converts two two-carbon acetyl units into the four-carbon succinate. The glyoxylate cycle is utilized by many bacteria, plants and fungi and allows these organisms to subsist on acetate or acetyl CoA yielding compounds. The pathway avoids the decarboxylation steps of the TCA cycle via the enzyme isocitrate lyase which cleaves isocitrate into succinate and glyoxylate. Generated succinate is then available for either energy production or biosynthesis.[22]: Section 17.4
GABA shunt
Succinate is the re-entry point for the
Cellular metabolism
Metabolic intermediate
Succinate is produced and concentrated in the mitochondria and its primary biological function is that of a metabolic intermediate.[6][22]: Section 17.1 All metabolic pathways that are interlinked with the TCA cycle, including the metabolism of carbohydrates, amino acids, fatty acids, cholesterol, and heme, rely on the temporary formation of succinate.[6] The intermediate is made available for biosynthetic processes through multiple pathways, including the reductive branch of the TCA cycle or the glyoxylate cycle, which are able to drive net production of succinate.[24][27] In rodents, mitochondrial concentrations are approximately ~0.5 mM[6] while plasma concentration are only 2–20 μM.[28]
ROS production
The activity of succinate dehydrogenase (SDH), which interconverts succinate into fumarate participates in mitochondrial
Additional biologic functions
 |
In addition to its metabolic roles, succinate serves as an intracellular and extracellular signaling molecule.
Transporters
Succinate requires specific transporters to move through both the mitochondrial and plasma membrane. Succinate exits the mitochondrial matrix and passes through the inner mitochondrial membrane via
Extracellular signaling
Extracellular succinate can act as a signaling molecule with hormone-like function, targeting a variety of tissues such as blood cells, adipose tissue, immune cells, the liver, the heart, the retina and primarily the kidney.
Effect on adipocytes
In adipocytes, the succinate-activated GPR91 signaling cascade inhibits lipolysis.[30]
Effect on the liver and retina
Succinate signaling often occurs in response to hypoxic conditions. In the liver, succinate serves as a
Effect on the heart
Extracellular succinate regulates
Effect on immune cells
SUCNR1 is highly expressed on immature
Effect on platelets
SUCNR1 is one of the highest expressed G protein-coupled receptors on human platelets, present at levels similar to P2Y12, though the role of succinate signaling in platelet aggregation is debated. Multiple studies have demonstrated succinate-induced aggregation, but the effect has high inter-individual variability.[28]
Effect on the kidneys
Succinate serves as a modulator of blood pressure by stimulating renin release in macula densa and juxtaglomerular apparatus cells via GPR91.[33] Therapies targeting succinate to reduce cardiovascular risk and hypertension are currently under investigation.[28]
Intracellular signaling
Accumulation of either fumarate or succinate reduces the activity of
Epigenetic effects
Succinate and fumarate inhibit the
Gene regulation
Succinate inhibition of
Role in human health
Inflammation
Metabolic signaling involving succinate can be involved in inflammation via stabilization of HIF1-alpha or GPR91 signaling in innate immune cells. Through these mechanisms, succinate accumulation has been shown to regulate production of inflammatory cytokines.[7] For dendritic cells, succinate functions as a chemoattractant and increases their antigen-presenting function via receptor stimulated cytokine production.[32] In inflammatory macrophages, succinate-induced stability of HIF1 results in increased transcription of HIF1-dependent genes, including the pro-inflammatory cytokine interleukin-1β.[39] Other inflammatory cytokines produced by activated macrophages such as tumor necrosis factor or interleukin 6 are not directly affected by succinate and HIF1.[7] The mechanism by which succinate accumulates in immune cells is not fully understood.[7] Activation of inflammatory macrophages through toll-like receptors induces a metabolic shift towards glycolysis.[40] In spite of a general downregulation of the TCA cycle under these conditions, succinate concentration is increased. However, lipopolysaccharides involved in the activation of macrophages increase glutamine and GABA transporters.[7] Succinate may thus be produced from enhanced glutamine metabolism via alpha-ketoglutarate or the GABA shunt.[citation needed]
Tumorigenesis
Succinate is one of three oncometabolites, metabolic intermediates whose accumulation causes metabolic and non-metabolic dysregulation implicated in
Ischemia reperfusion injury
Succinate accumulation under hypoxic conditions has been implicated in the
See also
- Flame retardant[43]
- Oil of amber, procured by heating succinic acid
- Citric acid cycle
- Metabolite
- Oncometabolism
References
- ^ ISBN 978-0-85404-182-4.
- ^ a b c d e Record in the GESTIS Substance Database of the Institute for Occupational Safety and Health
- ^ a b c d e f "Product Information Sheet: Succinic Acid" (PDF). Sigma Aldrich. Archived from the original (PDF) on 7 November 2017. Retrieved 7 November 2015.
- PMID 16246535.
- ^ a b c d "Succinic Acid". Toxnet National Library of Medicine HSDB Database. 2005-01-31. Retrieved 28 May 2017.
- ^ PMID 26971832.
- ^ PMID 24361092.
- ^ PMID 25383517.
- ^ "Definition of SUCCINYL". www.merriam-webster.com. Retrieved 2017-03-09.
- ^ ISBN 978-3527306732.
- ^ "NNFCC Renewable Chemicals Factsheet: Succinic Acid". 3 February 2010. Archived from the original on 20 July 2011.
- ^ PMID 21932253.
- PMID 23349810.
- .
- ^ "Top Value Added Chemicals from Biomass, Volume 1: Results of Screening for Potential Candidates from Sugars and Synthesis Gas" (PDF). U.S. Department of Energy. November 1, 2004. Archived (PDF) from the original on 2013-10-21. Retrieved 2013-11-12.
- ISBN 978-0-9522674-3-0
- ^ "1,4-Butanediol (BDO) Market Analysis By Application (Tetrahydrofuran, Polybutylene Teraphthalate, Gamma-Butyrolactone & Polyurethanes), And Segment Forecasts To 2020". Grand View Research. September 2015. Retrieved 2015-11-18.
- PMID 19924045.
- ^ "Succinic acid in the FDA SCOGS Database". FDA GRAS Database. 31 October 2015. Archived from the original on 31 October 2017. Retrieved 9 March 2020.
{{cite web}}: CS1 maint: bot: original URL status unknown (link) - S2CID 38868987.
- ^ "Overview of pharmaceutical excipients used in tablets and capsules". Modern Medicine Network. 24 October 2008. Archived from the original on 19 February 2012. Retrieved 7 November 2015.
- ^ a b c d Berg, JM; Tymoczko, JL; Stryer, L (2002). Biochemistry (5th ed.). New York: W H Freeman.
- ^ PMID 23333272.
- ^ PMID 23691505.
- ^ Peynaud, Emile (1984). Knowing and Making Wine.
- ^ PMID 26935843.
- ^ a b c Olsen, Richard W; DeLorey, Timothy M (1999). "GABA Synthesis, Uptake and Release". In Siegel, GJ; Agranoff, BW; Albers, RW; et al. (eds.). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Philadelphia: Lippincott-Raven.
- ^ PMID 22649411.
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- ^ PMID 27117029.
- S2CID 26263513.
- ^ Flame Retardant Finishing of Cotton Fleece Fabric: Part IV-Bifunctional Carboxylic Acids