Acitrate is a derivative of citric acid; that is, thesalts,esters, and thepolyatomic anion found in solutions and salts of citric acid. An example of the former, a salt istrisodium citrate; an ester istriethyl citrate. When citratetrianion is part of a salt, the formula of the citrate trianion is written asC 6H 5O3− 7 orC 3H 5O(COO)3− 3.
Lemons, oranges, limes, and other citrus fruits contain high concentrations of citric acid.
Citric acid occurs in a variety of fruits and vegetables, most notablycitrus fruits.Lemons andlimes have particularly high concentrations of the acid; it can constitute as much as 8% of the dry weight of these fruits (about 47 g/L in the juices[12]).[a] The concentrations of citric acid in citrus fruits range from 0.005 mol/L for oranges and grapefruits to 0.30 mol/L in lemons and limes; these values vary within species depending upon thecultivar and the circumstances under which the fruit was grown.
Citric acid was first isolated in 1784 by the chemistCarl Wilhelm Scheele, who crystallized it from lemon juice.[13][14]
Industrial-scale citric acid production first began in 1890 based on the Italian citrus fruit industry, where the juice was treated with hydrated lime (calcium hydroxide) to precipitatecalcium citrate, which was isolated and converted back to the acid using dilutedsulfuric acid.[15] In 1893,C. Wehmer discoveredPenicilliummold could produce citric acid from sugar.[16] However, microbial production of citric acid did not become industrially important until World War I disrupted ItalianCitrus exports.
In 1917, American food chemist James Currie discovered that certain strains of the moldAspergillus niger could be efficient citric acid producers,[17] and the pharmaceutical companyPfizer began industrial-level production using this technique two years later, followed byCitrique Belge in 1929. In this production technique, which is still the major industrial route to citric acid used today, cultures ofAspergillus niger are fed on asucrose orglucose-containing medium to produce citric acid. The source of sugar iscorn steep liquor,molasses, hydrolyzedcorn starch, or other inexpensive,carbohydrate solution.[18] After the mold is filtered out of the resultingsuspension, citric acid is isolated byprecipitating it with calcium hydroxide to yield calcium citrate salt, from which citric acid is regenerated by treatment with sulfuric acid, as in the direct extraction from citrus fruit juice.
In 1977, a patent was granted toLever Brothers for the chemical synthesis of citric acid starting either from aconitic or isocitrate (also called alloisocitrate) calcium salts under high pressure conditions; this produced citric acid in near quantitative conversion under what appeared to be a reverse, non-enzymaticKrebs cycle reaction.[19]
Global production was in excess of 2,000,000 tons in 2018.[20] More than 50% of this volume was produced in China. More than 50% was used as anacidity regulator in beverages, some 20% in other food applications, 20% for detergent applications, and 10% for applications other than food, such as cosmetics, pharmaceuticals, and in the chemical industry.[15]
Speciation diagram for a 10-millimolar solution of citric acid
Citric acid can be obtained as ananhydrous (water-free) form or as amonohydrate. The anhydrous form crystallizes from hot water, while the monohydrate forms when citric acid is crystallized from cold water. The monohydrate can be converted to the anhydrous form at about 78 °C. Citric acid also dissolves in absolute (anhydrous)ethanol (76 parts of citric acid per 100 parts of ethanol) at 15 °C. Itdecomposes with loss of carbon dioxide above about 175 °C.
Citric acid is a triproticacid, withpKa values, extrapolated to zero ionic strength, of 3.128, 4.761, and 6.396 at 25 °C.[21] The pKa of the hydroxyl group has been found, by means of13C NMR spectroscopy, to be 14.4.[22] The speciation diagram shows that solutions of citric acid arebuffer solutions between about pH 2 and pH 8. In biological systems around pH 7, the two species present are the citrate ion and mono-hydrogen citrate ion. The SSC 20X hybridization buffer is an example in common use.[23][24] Tables compiled for biochemical studies are available.[25]
Conversely, the pH of a 1 mM solution of citric acid will be about 3.2. The pH of fruit juices fromcitrus fruits like oranges and lemons depends on the citric acid concentration, with a higher concentration of citric acid resulting in a lower pH.
Acid salts of citric acid can be prepared by careful adjustment of the pH before crystallizing the compound. See, for example,sodium citrate.
The citrate ion forms complexes with metallic cations. Thestability constants for the formation of these complexes are quite large because of thechelate effect. Consequently, it forms complexes even with alkali metal cations. However, when a chelate complex is formed using all three carboxylate groups, the chelate rings have 7 and 8 members, which are generally less stable thermodynamically than smaller chelate rings. In consequence, the hydroxyl group can be deprotonated, forming part of a more stable 5-membered ring, as inammonium ferric citrate,[NH+4]5Fe3+(C6H4O4−7)2·2H2O.[26]
Citric acid can beesterified at one or more of its threecarboxylic acid groups to form any of a variety of mono-, di-, tri-, and mixed esters.[27]
Citrate is an intermediate in thecitric acid cycle, also known as thetricarboxylic acid (TCA)cycle or theKrebs cycle, a central metabolic pathway for animals, plants, and bacteria. In the Krebs cycle,citrate synthase catalyzes the condensation ofoxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate foraconitase and is converted intoaconitic acid. The cycle ends with regeneration of oxaloacetate. This series of chemical reactions is the source of two-thirds of the food-derived energy in higher organisms. The chemical energy released is available under the form ofAdenosine triphosphate (ATP).Hans Adolf Krebs received the 1953Nobel Prize in Physiology or Medicine for the discovery.
Citrate can be transported out of themitochondria and into the cytoplasm, then broken down intoacetyl-CoA forfatty acid synthesis, and into oxaloacetate. Citrate is a positive modulator of this conversion, andallosterically regulates the enzymeacetyl-CoA carboxylase, which is the regulating enzyme in the conversion of acetyl-CoA intomalonyl-CoA (the commitment step in fatty acid synthesis). In short, citrate is transported into the cytoplasm, converted into acetyl-CoA, which is then converted into malonyl-CoA by acetyl-CoA carboxylase, which is allosterically modulated by citrate.
High concentrations of cytosolic citrate can inhibitphosphofructokinase, the catalyst of a rate-limiting step ofglycolysis. This effect is advantageous: high concentrations of citrate indicate that there is a large supply of biosynthetic precursor molecules, so there is no need for phosphofructokinase to continue to send molecules of its substrate,fructose 6-phosphate, into glycolysis. Citrate acts by augmenting the inhibitory effect of high concentrations ofATP, another sign that there is no need to carry out glycolysis.[28]
Citrate is a vital component of bone, helping to regulate the size ofapatite crystals.[29]
Powdered citric acid being used to preparelemon pepper seasoning
Because it is one of the stronger edible acids, the dominant use of citric acid is as a flavoring and preservative in food and beverages, especially soft drinks and candies.[15] Within theEuropean Union it is denoted byE numberE330. Citrate salts of various metals are used to deliver those minerals in a biologically available form in manydietary supplements. Citric acid has 247 kcal per 100 g.[30] In the United States the purity requirements for citric acid as a food additive are defined by theFood Chemicals Codex, which is published by theUnited States Pharmacopoeia (USP).
Citric acid can be added to ice cream as an emulsifying agent to keep fats from separating, to caramel to prevent sucrose crystallization, or in recipes in place of fresh lemon juice. Citric acid is used withsodium bicarbonate in a wide range ofeffervescent formulae, both for ingestion (e.g., powders and tablets) and for personal care (e.g.,bath salts,bath bombs, and cleaning ofgrease). Citric acid sold in a dry powdered form is commonly sold in markets and groceries as "sour salt", due to its physical resemblance to table salt. It has use in culinary applications, as an alternative to vinegar or lemon juice, where a pure acid is needed. Citric acid can be used infood coloring to balance the pH level of a normally basic dye.[citation needed]
Citric acid is an excellentchelating agent, binding metals by making them soluble. It is used to remove and discourage the buildup oflimescale from boilers and evaporators.[15] It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. By chelating the metals inhard water, it lets these cleaners produce foam and work better without need for water softening. Citric acid is the active ingredient in some bathroom and kitchen cleaning solutions. A solution with a six percent concentration of citric acid will remove hard water stains from glass without scrubbing. Citric acid can be used in shampoo to wash out wax and coloring from the hair. Illustrative of its chelating abilities, citric acid was the first successfuleluant used for total ion-exchange separation of thelanthanides, during theManhattan Project in the 1940s.[33] In the 1950s, it was replaced by the far more efficient[34]EDTA.
Citric acid is used as anacidulant in creams, gels, and liquids. Used in foods and dietary supplements, it may be classified as a processing aid if it was added for a technical or functional effect (e.g. acidulent, chelator, viscosifier, etc.). If it is still present in insignificant amounts, and the technical or functional effect is no longer present, it may be exempt from labeling <21 CFR §101.100(c)>.
Citric acid is analpha hydroxy acid and is an active ingredient in chemical skin peels.[36]
Citric acid is commonly used as a buffer to increase the solubility of brownheroin.[37]
Citric acid is used as one of the active ingredients in the production of facial tissues with antiviral properties.[38]
Citric acid can be used as a lower-odorstop bath as part of the process for developingphotographic film.Photographic developers are alkaline, so a mild acid is used to neutralize and stop their action quickly, but commonly usedacetic acid leaves a strong vinegar odor in the darkroom.[41]
Citric acid is an excellentsolderingflux,[42] either dry or as a concentrated solution in water. It should be removed after soldering, especially with fine wires, as it is mildly corrosive. It dissolves and rinses quickly in hot water.
Alkali citrate can be used as an inhibitor of kidney stones by increasing urine citrate levels, useful for prevention of calcium stones, and increasing urine pH, useful for preventing uric acid and cystine stones.[43]
Citric acid is a versatile precursor to many other organic compounds. Dehydration routes giveitaconic acid and its anhydride.[44]Citraconic acid can be produced via thermal isomerization of itaconic acid anhydride.[45] The required itaconic acid anhydride is obtained by dry distillation of citric acid.Aconitic acid can be synthesized by dehydration of citric acid usingsulfuric acid:[46]
Although a weak acid, exposure to pure citric acid can cause adverse effects. Inhalation may cause cough, shortness of breath, or sore throat. Over-ingestion may cause abdominal pain and sore throat. Exposure of concentrated solutions to skin and eyes can cause redness and pain.[48] Long-term or repeated consumption may cause erosion oftooth enamel.[48][49][50]
^This still does not make the lemon particularly strongly acidic. This is because, as a weak acid, most of the acid molecules are not dissociated so not contributing to acidity inside the lemon or its juice.
^Silva, Andre M. N.; Kong, Xiaole; Hider, Robert C. (2009). "Determination of the pKa value of the hydroxyl group in the α-hydroxycarboxylates citrate, malate and lactate by 13C NMR: implications for metal coordination in biological systems".BioMetals.22 (5):771–778.doi:10.1007/s10534-009-9224-5.ISSN0966-0844.PMID19288211.
^abcCitric acid in Linstrom, Peter J.; Mallard, William G. (eds.);NIST Chemistry WebBook, NIST Standard Reference Database Number 69, National Institute of Standards and Technology, Gaithersburg (MD) (retrieved 2014-06-02)
^Scheele, Carl Wilhelm (1784)."Anmärkning om Citron-saft, samt sätt at crystallisera densamma" [Note about lemon juice, as well as ways to crystallize it].Kungliga Vetenskaps Academiens Nya Handlingar [New Proceedings of the Royal Academy of Science]. 2nd series (in Swedish).5:105–109.
^Silva, Andre M. N.; Kong, Xiaole; Hider, Robert C. (2009). "Determination of the pKa value of the hydroxyl group in the α-hydroxycarboxylates citrate, malate and lactate by13C NMR: implications for metal coordination in biological systems".Biometals.22 (5):771–778.doi:10.1007/s10534-009-9224-5.PMID19288211.S2CID11615864.
^Matzapetakis, M.; Raptopoulou, C. P.; Tsohos, A.; Papaefthymiou, V.; Moon, S. N.; Salifoglou, A. (1998). "Synthesis, Spectroscopic and Structural Characterization of the First Mononuclear, Water Soluble Iron−Citrate Complex, (NH4)5Fe(C6H4O7)2·2H2O".J. Am. Chem. Soc.120 (50):13266–13267.doi:10.1021/ja9807035.
^Bergeron, Raymond J.; Xin, Meiguo; Smith, Richard E.; Wollenweber, Markus; McManis, James S.; Ludin, Christian; Abboud, Khalil A. (1997). "Total synthesis of rhizoferrin, an iron chelator".Tetrahedron.53 (2):427–434.doi:10.1016/S0040-4020(96)01061-7.
^Greenfield, Heather; Southgate, D.A.T. (2003).Food Composition Data: Production, Management and Use. Rome:FAO. p. 146.ISBN9789251049495.
^Xiang Hao, Yongge Wei, Shiwei Zhang (2001): "Synthesis, crystal structure and magnetic property of a binuclear iron(III) citrate complex".Transition Metal Chemistry, volume 26, issue 4, pages 384–387.doi:10.1023/A:1011055306645
^Shweky, Itzhak; Bino, Avi; Goldberg, David P.; Lippard, Stephen J. (1994). "Syntheses, Structures, and Magnetic Properties of Two Dinuclear Iron(III) Citrate Complexes".Inorganic Chemistry.33 (23):5161–5162.doi:10.1021/ic00101a001.
^Strang J, Keaney F, Butterworth G, Noble A, Best D (April 2001). "Different forms of heroin and their relationship to cook-up techniques: data on, and explanation of, use of lemon juice and other acids".Subst Use Misuse.36 (5):573–88.doi:10.1081/ja-100103561.PMID11419488.S2CID8516420.
^ab"Citric acid".International Chemical Safety Cards.NIOSH. September 18, 2018. Archived fromthe original on July 12, 2018. RetrievedSeptember 9, 2017.
^J. Zheng; F. Xiao; L. M. Qian; Z. R. Zhou (December 2009). "Erosion behavior of human tooth enamel in citric acid solution".Tribology International.42 (11–12):1558–1564.doi:10.1016/j.triboint.2008.12.008.
