Succinic acid is a four-carbon acyclic dicarboxylic acid. It is a white, odorless solid with a highly acidic taste. It is used as a flavoring agent, contributing a sour and astringent component characteristic of the umami taste (PMID:21932253). The anion, succinate, is a key component of the citric acid or TCA cycle and is capable of donating electrons to the electron transfer chain. Succinate dehydrogenase (SDH) plays an important role in mitochondrial function, being both part of the respiratory chain and the Krebs cycle. SDH, with a covalently attached FAD prosthetic group, is able to bind several different enzyme substrates (succinate and fumarate) and physiological regulators (oxaloacetate and ATP). Oxidizing succinate links SDH to the fast-cycling Krebs cycle portion where it participates in the breakdown of acetyl-CoA throughout the entire Krebs cycle. Succinate can readily be imported into the mitochondrial matrix by the n-butyl malonate- (or phenyl succinate-) sensitive dicarboxylate carrier in exchange with inorganic phosphate or another organic acid, e. g. malate (PMID:16143825). Human mutations in the four genes encoding the subunits of the mitochondrial succinate dehydrogenase are associated with a wide spectrum of clinical presentations, i.e.: Huntington’s disease (PMID:11803021). Moreover, succinic acid is found to be associated with D-2-hydroxyglutaric aciduria, which is an inborn error of metabolism. Additionally, succinic acid has been identified as an oncometabolite or an endogenous cancer-causing metabolite. Oncoetabolites are metabolic intermediates whose accumulation causes a metabolic and non-metabolic dysregulation leading to tumorigenesis. (PMID:23999438, PMID:27117029). High levels of succinic acid can be found in tumors or biofluids surrounding tumors. Its oncogenic action appears due to its ability to inhibit prolyl hydroxylase domain-containing enzymes. In many tumours, oxygen availability becomes limited (hypoxia) very quickly due to rapid cell proliferation and limited blood vessel growth. The major regulator of the response to hypoxia is the HIF transcription factor (HIF-alpha). Under normal oxygen levels, protein levels of HIF-alpha are very low due to constant degradation, mediated by a series of post-translational modification events catalyzed by the prolyl hydroxylase domain-containing enzymes PHD1, 2 and 3, (also known as EglN2, 1 and 3) that hydroxylate HIF-alpha and lead to its degradation. All three of the PHD enzymes are inhibited by succinate. Succinic acid has been found to be associated with D-2-hydroxyglutaric aciduria, which is an inborn error of metabolism. Succinic acid is also a microbial metabolite. Indeed, urinary succinic acid is produced by Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterobacter sp., Acinetobacter sp., Proteus mirabilis, Citrobactes frundii, Enterococcus faecalis (PMID:22292465). Succinic acid is also found in Actinobacillus, Anaerobiospirillum, Mannheimia, Corynebacterium and Basfia (PMID:22292465; PMID:18191255; PMID:26360870). Succinic acid, or its anion succinate, is used as an excipient in pharmaceutical products to control acidity or as a counter ion. Drugs involving succinate include metoprolol succinate, sumatriptan succinate, Doxylamine succinate or solifenacin succinate. In 2004, succinic acid was identified by the Department of Energy of the United States of America as one of twelve molecules that can be produced from plant sugars through biological or chemical processes and that have a potential to subsequently be converted to a number of high-value bio-based chemicals or materials. In this regard, industrial hemp (Cannabis sativa L.) has been identified as a source of succinic acid after several chemical and biological treatments (PMID:25682224), suggessting it could serve as a promising source of building blocks for green chemistry products.
Belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
Turner CE, Elsohly MA, Boeren EG: Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod. 1980 Mar-Apr;43(2):169-234. doi: 10.1021/np50008a001. [PubMed:6991645]
Thakker C, Martinez I, San KY, Bennett GN: Succinate production in Escherichia coli. Biotechnol J. 2012 Feb;7(2):213-24. doi: 10.1002/biot.201100061. Epub 2011 Sep 20. [PubMed:21932253]
Briere JJ, Favier J, El Ghouzzi V, Djouadi F, Benit P, Gimenez AP, Rustin P: Succinate dehydrogenase deficiency in human. Cell Mol Life Sci. 2005 Oct;62(19-20):2317-24. doi: 10.1007/s00018-005-5237-6. [PubMed:16143825]
Rustin P, Rotig A: Inborn errors of complex II--unusual human mitochondrial diseases. Biochim Biophys Acta. 2002 Jan 17;1553(1-2):117-22. doi: 10.1016/s0005-2728(01)00228-6. [PubMed:11803021]
Yang M, Soga T, Pollard PJ: Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep;123(9):3652-8. doi: 10.1172/JCI67228. Epub 2013 Sep 3. [PubMed:23999438]
Gupta A, Dwivedi M, Mahdi AA, Khetrapal CL, Bhandari M: Broad identification of bacterial type in urinary tract infection using (1)h NMR spectroscopy. J Proteome Res. 2012 Mar 2;11(3):1844-54. doi: 10.1021/pr2010692. Epub 2012 Jan 31. [PubMed:22292465]
Sauer M, Porro D, Mattanovich D, Branduardi P: Microbial production of organic acids: expanding the markets. Trends Biotechnol. 2008 Feb;26(2):100-8. doi: 10.1016/j.tibtech.2007.11.006. Epub 2008 Jan 11. [PubMed:18191255]
Becker J, Lange A, Fabarius J, Wittmann C: Top value platform chemicals: bio-based production of organic acids. Curr Opin Biotechnol. 2015 Dec;36:168-75. doi: 10.1016/j.copbio.2015.08.022. Epub 2015 Sep 8. [PubMed:26360870]
Gunnarsson IB, Kuglarz M, Karakashev D, Angelidaki I: Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.). Bioresour Technol. 2015 Apr;182:58-66. doi: 10.1016/j.biortech.2015.01.126. Epub 2015 Feb 4. [PubMed:25682224]
Only showing the first 10 proteins. There are83 proteins in total.
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Can act as a tumor suppressor.
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (By similarity).
Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-5 carbon atoms. The stoichiometry is probably 3 Na(+) for 1 divalent succinate
