1.0 2020-03-18 23:22:03 UTC 2022-12-13 23:36:28 UTC CDB006159 Citric acid Citric acid (citrate) is a weak tricarboxylic acid that is formed in the tricarboxylic acid cycle. In humans citric acid is produced endogenously or it may be introduced with diet, with citrus fruits being a key source. Citrate is produced by all aerobic organisms, from microbes to humans. Citrate is formed in the TCA cycle via the enzyme known as citrate synthase, which catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate for aconitase and is converted into aconitic acid. Some bacteria (notably E. coli) can produce and consume citrate internally as part of their TCA cycle, but are unable to use it as food because they lack the enzymes required to import it into the cell. Citrate has a number of biological roles in humans. In particular, it can be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis. Citrate can also acts as a signalling molecule. High concentrations of cytosolic citrate can inhibit phosphofructokinase, the catalyst of a rate-limiting step of glycolysis. Inhibition of glycolysis has been shown to suppress tumor growth in a number of animal models ( PMID: 28674429). Citrate is also a vital component of bone, helping to regulate the size of apatite crystals. Urinary citrate levels can be used to identify a number of disorders. Indeed urinary citrate excretion is a common tool in the differential diagnosis of kidney stones, renal tubular acidosis and it plays also a role in characterizing bone diseases such as osteoporosis (PMID 12957820). The secretory epithelial cells of the prostate gland of humans and other animals possess a unique citrate-related metabolic pathway regulated by testosterone and prolactin. This specialized hormone-regulated metabolic activity is responsible for the major prostate function of the production and secretion of extraordinarily high levels of citrate. The key regulatory enzymes directly associated with citrate production in the prostate cells are mitochondrial aspartate aminotransferase, pyruvate dehydrogenase, and mitochondrial aconitase. Testosterone and prolactin are involved in the regulation of the corresponding genes associated with these enzymes (PMID 12198595). In addition to its biological roles and endogenous production, citrate is obtained from many other sources and used in many applications. Citric acid is found in citrus fruits, most concentrated in lemons and limes, where it can comprise as much as 8% of the dry weight of the fruit. The concentrations of citric acid in citrus fruits range from 5 mM for oranges and grapefruits to 300 mM in lemons and limes. However, these values vary within species depending upon the cultivar and the circumstances in which the fruit was grown. Citric acid is a natural preservative and is also used to add an acidic (sour) taste to foods and soft drinks. Citric acid is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. Citric acid is also used as an acidulant in creams, gels, and liquids. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. Intolerance to citric acid in the diet is known to exist. Altered levels of citric acid have been found to be associated with maple syrup urine disease, primary hypomagnesemia, propionic acidemia, and tyrosinemia I, which are inborn errors of metabolism. 2-Hydroxy-1,2,3-propanetricarboxylic acid 2-Hydroxytricarballylic acid 3-Carboxy-3-hydroxypentane-1,5-dioic acid Citronensaeure e330 H3Cit Anhydrous citric acid Citric acid anhydrous 2-Hydroxy-1,2,3-propanetricarboxylate 2-Hydroxytricarballylate 3-Carboxy-3-hydroxypentane-1,5-dioate Anhydrous citrate Citrate anhydrous Citrate Aciletten beta-Hydroxytricarballylate beta-Hydroxytricarballylic acid Chemfill Citraclean Citretten Citro e 330 Hydrocerol a Kyselina citronova Suby g Uro-trainer Acid monohydrate, citric Monohydrate, citric acid Citric acid, anhydrous Citric acid monohydrate Uralyt u C6H8O7 192.12 192.027 2-hydroxypropane-1,2,3-tricarboxylic acid citric acid 77-92-9 OC(=O)CC(O)(CC(O)=O)C(O)=O InChI=1S/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12) KRKNYBCHXYNGOX-UHFFFAOYSA-N belongs to the class of organic compounds known as tricarboxylic acids and derivatives. These are carboxylic acids containing exactly three carboxyl groups. Tricarboxylic acids and derivatives Organic compounds Organic acids and derivatives Carboxylic acids and derivatives Tricarboxylic acids and derivatives Aliphatic acyclic compounds Alpha hydroxy acids and derivatives Carbonyl compounds Carboxylic acids Hydrocarbon derivatives Organic oxides Tertiary alcohols Alcohol Aliphatic acyclic compound Alpha-hydroxy acid Carbonyl group Carboxylic acid Hydrocarbon derivative Hydroxy acid Organic oxide Organic oxygen compound Organooxygen compound Tertiary alcohol Tricarboxylic acid or derivatives tricarboxylic acid water_solubility 592.0 mg/mL logp -1.64 AVDEEF,A (1997) melting_point 153 °C boiling_point 310 °C Wikipedia logp -1.33 ALOGPS logs -0.26 ALOGPS logp -1.3 ChemAxon pka_strongest_acidic 3.05 ChemAxon pka_strongest_basic -4.2 ChemAxon iupac 2-hydroxypropane-1,2,3-tricarboxylic acid ChemAxon average_mass 192.12 ChemAxon mono_mass 192.027 ChemAxon smiles OC(=O)CC(O)(CC(O)=O)C(O)=O ChemAxon formula C6H8O7 ChemAxon inchi InChI=1S/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12) ChemAxon inchikey KRKNYBCHXYNGOX-UHFFFAOYSA-N ChemAxon polar_surface_area 132.13 ChemAxon refractivity 35.62 ChemAxon polarizability 15.54 ChemAxon rotatable_bond_count 5 ChemAxon acceptor_count 7 ChemAxon donor_count 4 ChemAxon physiological_charge -3 ChemAxon formal_charge 0 ChemAxon number_of_rings 0 ChemAxon bioavailability 1 ChemAxon rule_of_five Yes ChemAxon ghose_filter Yes ChemAxon veber_rule Yes ChemAxon mddr_like_rule Yes ChemAxon C00158 FDB030735 DB04272 305 311 30769 C00007619 CIT Citric_Acid 34080 124 Ren JG, Seth P, Ye H, Guo K, Hanai JI, Husain Z, Sukhatme VP: Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway. Sci Rep. 2017 Jul 3;7(1):4537. doi: 10.1038/s41598-017-04626-4. 28674429 Caudarella R, Vescini F, Buffa A, Stefoni S: Citrate and mineral metabolism: kidney stones and bone disease. Front Biosci. 2003 Sep 1;8:s1084-106. doi: 10.2741/1119. 12957820 Costello LC, Franklin RB: Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm Metab Res. 2002 Aug;34(8):417-24. doi: 10.1055/s-2002-33598. 12198595