Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Citric acid: Difference between pages

{{short description|Weak organic acid}}

{{redirect|E330|the locomotive|FS Class E330}}

{{Use mdy dates|date=April 2012}}

|Name = Citric acid

|ImageFileL1 = Zitronensäure - Citric acid.svg

|ImageSizeL1 = 150px

|ImageNameL1 = Stereo skeletal formula of citric acid

|ImageFileR1 = Citric-acid-3D-balls.png

|ImageSizeR1 = 150px

|ImageNameR1 = Ball-and-stick model of citric acid

|ImageFile2 = Zitronensäure Kristallzucht.jpg

|ImageSize2 = 320px

|ImageName2 = Crystal sample from the saturated citric acid solution.

|IUPACName = Citric acid<ref name="IUPAC2014">{{cite book |author=[[International Union of Pure and Applied Chemistry]] |date=2014 |title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 |publisher=[[Royal Society of Chemistry|The Royal Society of Chemistry]] |pages=747 |doi=10.1039/9781849733069 |isbn=978-0-85404-182-4}}</ref>

|PIN = 2-Hydroxypropane-1,2,3-tricarboxylic acid<ref name="IUPAC2014"/>

|Section1 = {{Chembox Identifiers

|IUPHAR_ligand = 2478

|PubChem = 311

|PubChem1 = 22230

|PubChem1_Comment = (monohydrate)

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = XF417D3PSL

|KEGG_Ref = {{keggcite|correct|kegg}}

|KEGG = D00037

|InChI = 1/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)

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 30769

|DrugBank_Ref = {{drugbankcite|correct|drugbank}}

|DrugBank = DB04272

|SMILES = OC(=O)CC(O)(C(=O)O)CC(=O)O

|InChIKey = KRKNYBCHXYNGOX-UHFFFAOYAM

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 1261

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 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)

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = KRKNYBCHXYNGOX-UHFFFAOYSA-N

|CASNo = 77-92-9

|CASNo_Ref = {{cascite|correct|CAS}}

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 305

|RTECS = GE7350000

|EINECS = 201-069-1

|Section2 = {{Chembox Properties

|Formula = {{chem2|C6H8O7}}

|C=6 | H=8 | O=7

|Appearance = white solid

|Odor = Odorless

|MolarMass = 192.123{{nbsp}}g/mol (anhydrous), 210.14{{nbsp}}g/mol (monohydrate)<ref>{{PubChemLink|22230}}</ref>

|Density = 1.665{{nbsp}}g/cm³ (anhydrous)<br /> 1.542{{nbsp}}g/cm³ (18{{nbsp}}°C, monohydrate)

|Solubility = 54%{{nbsp}}w/w (10{{nbsp}}°C)<br /> 59.2%{{nbsp}}w/w (20{{nbsp}}°C)<br /> 64.3%{{nbsp}}w/w (30{{nbsp}}°C)<br /> 68.6%{{nbsp}}w/w (40{{nbsp}}°C)<br /> 70.9%{{nbsp}}w/w (50{{nbsp}}°C)<br /> 73.5%{{nbsp}}w/w (60{{nbsp}}°C)<br /> 76.2%{{nbsp}}w/w (70{{nbsp}}°C)<br /> 78.8%{{nbsp}}w/w (80{{nbsp}}°C)<br /> 81.4%{{nbsp}}w/w (90{{nbsp}}°C)<br /> 84%{{nbsp}}w/w (100{{nbsp}}°C)<ref name=pubchem>{{PubChemLink|311}}</ref>

|SolubleOther = Soluble in [[acetone]], [[ethanol|alcohol]], [[diethyl ether|ether]], [[ethyl acetate]], [[dimethyl sulfoxide|DMSO]]<br /> Insoluble in [[benzene|{{chem|C|6|H|6}}]], [[chloroform|CHCl₃]], [[carbon disulfide|CS₂]], [[toluene]]<ref name=chemister />

|Solubility1 = 62{{nbsp}}g/100{{nnbsp}}g (25{{nbsp}}°C)<ref name=chemister />

|Solvent1 = ethanol

|Solubility2 = 4.41{{nbsp}}g/100{{nnbsp}}g (25{{nbsp}}°C)<ref name=chemister />

|Solvent2 = amyl acetate

|Solubility3 = 1.05{{nbsp}}g/100{{nnbsp}}g (25{{nbsp}}°C)<ref name=chemister />

|Solvent3 = diethyl ether

|Solubility4 = 35.9{{nbsp}}g/100{{nnbsp}}g (25{{nbsp}}°C)<ref name=chemister />

|Solvent4 = 1,4-dioxane

|MeltingPtC = 156

|BoilingPtC = 310

|BoilingPt_notes = decomposes from 175{{nbsp}}°C<ref name=chemister>{{cite web|url=http://chemister.ru/Database/properties-en.php?dbid=1&id=1624|title=citric acid|work=chemister.ru|access-date=June 1, 2014|archive-url=https://web.archive.org/web/20141129151027/http://chemister.ru/Database/properties-en.php?dbid=1&id=1624|archive-date=November 29, 2014|url-status=dead}}</ref>

|pKa = p''K''_a1 = 3.13<ref name="sigma" /><br /> p''K''_a2 = 4.76<ref name="sigma" /><br /> p''K''_a3 = 6.39,<ref>

{{cite web |url=http://www.zirchrom.com/organic.htm |title=Data for Biochemical Research |publisher=ZirChrom Separations, Inc |access-date=January 11, 2012}}</ref> 6.40<ref>

{{cite web |url=http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/acidity2.htm |title=Ionization Constants of Organic Acids |publisher=Michigan State University |access-date=January 11, 2012}}</ref><br/>p''K''_a4 = 14.4<ref name="Silva Kong Hider 2009 pp. 771–778">{{cite journal | last1=Silva | first1=Andre M. N. | last2=Kong | first2=Xiaole | last3=Hider | first3=Robert C. | title=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 | journal=BioMetals | volume=22 | issue=5 | date=2009 | issn=0966-0844 | doi=10.1007/s10534-009-9224-5 | pages=771–778| pmid=19288211 }}</ref>

|LogP = −1.64

|RefractIndex = 1.493–1.509 (20{{nbsp}}°C)<ref name=pubchem /><br /> 1.46 (150{{nbsp}}°C)<ref name=chemister />

|Viscosity = 6.5{{nbsp}}cP (50% {{abbr|aq. sol.|aqueous solution}})<ref name=pubchem />

}}

|Section3 = {{Chembox Structure

|CrystalStruct = Monoclinic

}}

|Section4 = {{Chembox Thermochemistry

|DeltaHf = −1543.8{{nbsp}}kJ/mol<ref name=pubchem />

|HHV = 1985.3 kJ/mol (474.5 kcal/mol, 2.47&nbsp;kcal/g),<ref name=pubchem /> 1960.6{{nbsp}}kJ/mol<ref name=nist>{{nist|name=Citric acid|id=C77929|accessdate=2014-06-02|mask=FFFF|units=SI}}</ref><br /> 1972.34 kJ/mol (471.4&nbsp;kcal/mol, 2.24&nbsp;kcal/g) (monohydrate)<ref name=pubchem />

|Entropy = 252.1{{nbsp}}J/(mol·K)<ref name=nist />

|HeatCapacity = 226.51{{nbsp}}J/(mol·K) (26.85{{nbsp}}°C)<ref name=nist />

}}

|Section5 = {{Chembox Pharmacology

|ATCCode_prefix = A09

|ATCCode_suffix = AB04

}}

|Section6 = {{Chembox Hazards

|ExternalSDS = [http://www.hmdb.ca/system/metabolites/msds/000/000/065/original/HMDB00094.pdf?1358893891 HMDB] (PDF)

|GHSPictograms = {{GHS corrosion}}{{GHS exclamation mark}}<ref name="sigma">[[Fisher Scientific]], [http://www.sigmaaldrich.com/catalog/product/sial/251275 Citric acid]. Retrieved on 2014-06-02.</ref>

|GHSSignalWord = Warning

|HPhrases = {{H-phrases|290}}, {{H-phrases|319}}, {{H-phrases|315}}<ref name="sigma" />

|PPhrases = {{P-phrases|305+351+338}}<ref name="sigma" />

|NFPA-H = 2

|NFPA-F = 1

|NFPA-R = 0

|MainHazards = Skin and eye irritant

|FlashPtC = 155

|AutoignitionPtC = 345

|ExploLimits = 8%<ref name="sigma" />

|LD50 = 3000{{nbsp}}mg/kg (rats, oral)

}}

}}

'''Citric acid''' is an [[organic compound]] with the [[skeletal formula]] {{chem2|HOC(CO2H)(CH2CO2H)2|auto=1}}.<ref name=:1/> It is a [[Transparency and translucency|colorless]] [[Weak acid|weak]] [[organic acid]].<ref name=:1/> It occurs naturally in [[Citrus|citrus fruits]]. In [[biochemistry]], it is an intermediate in the [[citric acid cycle]], which occurs in the [[metabolism]] of all [[aerobic organism]]s.<ref name=:1>{{Cite web |url=https://pubchem.ncbi.nlm.nih.gov/compound/citric_acid/ |title=Citric acid &#124; C6H8O7 - PubChem |access-date=December 19, 2021 |archive-date=January 19, 2022 |archive-url=https://web.archive.org/web/20220119023922/https://pubchem.ncbi.nlm.nih.gov/compound/citric_acid |url-status=dead }}</ref>

More than two million tons of citric acid [[Commodity chemicals|are manufactured]] every year. It is used widely as an [[acidifier]], as a [[flavoring]], and a [[chelating agent]].<ref>{{cite book |last1=Apleblat |first1=Alexander |title=Citric acid |date=2014 |publisher=Springer |isbn=978-3-319-11232-9}}</ref>

A '''citrate''' is a derivative of citric acid; that is, the [[salt (chemistry)|salts]], [[ester]]s, and the [[polyatomic ion|polyatomic anion]] found in solutions and salts of citric acid. An example of the former, a salt is [[trisodium citrate]]; an ester is [[triethyl citrate]]. When citrate [[anion|trianion]] is part of a salt, the formula of the citrate trianion is written as {{chem|C|6|H|5|O|7|3-}} or {{chem|C|3|H|5|O(COO)|3|3-}}.

==Natural occurrence and industrial production==

[[File:Citrus fruits.jpg|alt=|left|thumb|Lemons, oranges, limes, and other citrus fruits contain high concentrations of citric acid.]]

Citric acid occurs in a variety of fruits and vegetables, most notably [[Citrus|citrus fruit]]s. [[Lemon]]s and [[Lime (fruit)|limes]] have particularly high concentrations of the acid; it can constitute as much as 8% of the dry weight of these fruits (about 47&nbsp;g/L in the juices<ref>{{cite journal |vauthors=Penniston KL, Nakada SY, Holmes RP, Assimos DG| title=Quantitative Assessment of Citric Acid in Lemon Juice, Lime Juice, and Commercially-Available Fruit Juice Products | journal=Journal of Endourology | volume=22 | issue=3 | year=2008 | pmid=18290732 | pages = 567–570 | doi = 10.1089/end.2007.0304 | pmc=2637791}}</ref>).{{efn|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.}} The concentrations of citric acid in citrus fruits range from 0.005&nbsp;[[molarity|mol/L]] for oranges and grapefruits to 0.30&nbsp;mol/L in lemons and limes; these values vary within species depending upon the [[cultivar]] and the circumstances under which the fruit was grown.

Citric acid was first isolated in 1784 by the chemist [[Carl Wilhelm Scheele]], who crystallized it from lemon juice.<ref>{{cite journal |last1=Scheele |first1=Carl Wilhelm |title=Anmärkning om Citron-saft, samt sätt at crystallisera densamma |journal=Kungliga Vetenskaps Academiens Nya Handlingar [New Proceedings of the Royal Academy of Science] |date=1784 |volume=5 |pages=105–109 |url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015009215438;view=1up;seq=115 |series=2nd series |trans-title=Note about lemon juice, as well as ways to crystallize it |language=sv}}</ref><ref name="book1">{{cite book|last=Graham|first=Thomas|title=Elements of chemistry, including the applications of the science in the arts|url=https://archive.org/details/elementschemist00grahgoog|access-date=June 4, 2010|year=1842|publisher=Hippolyte Baillière, foreign bookseller to the Royal College of Surgeons, and to the Royal Society, 219, Regent Street.|page=[https://archive.org/details/elementschemist00grahgoog/page/n973 944]}}</ref>

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 precipitate [[calcium citrate]], which was isolated and converted back to the acid using diluted [[sulfuric acid]].<ref name="ullmann" /> In 1893, [[Carl Wehmer (chemist)|C. Wehmer]] discovered ''[[Penicillium]]'' [[Mold (fungus)|mold]] could produce citric acid from sugar.<ref>{{cite book |url=https://books.google.com/books?id=fdBMcYg_xGYC&pg=PA140 |title=A History of Lactic Acid Making: A Chapter in the History of Biotechnology |author=H. Benninga |date=30 June 1990 |publisher=Springer Science & Business Media |isbn=978-0-7923-0625-2 |pages=140–5}}</ref> However, microbial production of citric acid did not become industrially important until World War I disrupted Italian citrus exports.

In 1917, American food chemist James Currie discovered that certain strains of the mold ''[[Aspergillus niger]]'' could be efficient citric acid producers,<ref>{{Cite book |last=Currie |first=James |url=https://books.google.com/books?id=7q8BAAAAYAAJ&pg=PA15 |title=The Journal of Biological Chemistry |publisher=American Society for Biochemistry and Molecular Biology |year=1917 |pages=15–27 |language=en}}</ref> and the pharmaceutical company [[Pfizer]] began industrial-level production using this technique two years later, followed by [[Citrique Belge]] in 1929.

In this production technique, which is still the major industrial route to citric acid used today, cultures of ''Aspergillus niger'' are fed on a [[sucrose]] or [[glucose]]-containing medium to produce citric acid. The source of sugar is [[corn steep liquor]], [[molasses]], hydrolyzed [[corn starch]], or other inexpensive, [[carbohydrate]] solution.<ref>{{cite journal |first1=Walid A. |last1=Lotfy |first2=Khaled M. |last2=Ghanem |first3=Ehab R. |last3=El-Helow |year=2007 |url=https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Citric+acid+production+by+a+novel+Aspergillus+niger+isolate%3A+II.+Optimization+of+process+parameters+through+statistical+experimental+designs&btnG= |format=PDF |title=Citric acid production by a novel ''Aspergillus niger'' isolate: II. Optimization of process parameters through statistical experimental designs |journal=Bioresource Technology |volume=98 |issue=18 |pages=3470–3477 |doi=10.1016/j.biortech.2006.11.032 |pmid=17317159|bibcode=2007BiTec..98.3470L }}</ref> After the mold is filtered out of the resulting [[Suspension (chemistry)|suspension]], citric acid is isolated by [[Precipitation (chemistry)|precipitating]] 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 to [[Lever 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-enzymatic [[Krebs cycle reaction]].<ref>{{cite web |last1=Lamberti |first1=Vincent |last2=Gutierrez |first2=Eddie N. |title=Chemical processes for preparing citric acid |url=https://patents.google.com/patent/US4056567A/en |website=Google Patents |access-date=4 August 2024 |date=1 November 1977}} (US 4056567)</ref>

Global production was in excess of 2,000,000 tons in 2018.<ref>{{cite web |url=https://www.prnewswire.com/news-releases/global-citric-acid-markets-report-2011-2018--2019-2024-300814817.html |title=Global Citric Acid Markets Report, 2011-2018 & 2019-2024 |date= 19 March 2019 |website=prnewswire.com |access-date=28 October 2019}}</ref> More than 50% of this volume was produced in China. More than 50% was used as an [[acidity 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.<ref name="ullmann">{{Ullmann | title = Citric Acid | first1 = Frank H.|last1=Verhoff|first2=Hugo|last2=Bauweleers|year=2014|doi=10.1002/14356007.a07_103.pub3}}</ref>

==Chemical characteristics==

[[File:Citric acid speciation.svg|thumb|left|[[Ion speciation|Speciation]] diagram for a 10-millimolar solution of citric acid]]

Citric acid can be obtained as an [[anhydrous]] (water-free) form or as a [[hydrate|monohydrate]]. 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&nbsp;°C. Citric acid also dissolves in absolute (anhydrous) [[ethanol]] (76 parts of citric acid per 100 parts of ethanol) at 15&nbsp;°C. It [[decarboxylation|decomposes]] with loss of carbon dioxide above about 175&nbsp;°C.

Citric acid is a tribasic [[acid]], with [[Acid dissociation constant|pK_a]] values, extrapolated to zero ionic strength, of 3.128, 4.761, and 6.396 at 25&nbsp;°C.<ref>{{cite journal

| first1= Robert N.| last1= Goldberg| first2= Nand| last2= Kishore| first3= Rebecca M.| last3= Lennen| s2cid= 94614267 |url=https://www.nist.gov/system/files/documents/srd/jpcrd615.pdf#page=35&zoom=auto,-76,487 |title= Thermodynamic Quantities for the Ionization Reactions of Buffers| journal= J. Phys. Chem. Ref. Data| year = 2002| volume= 31| issue= 1| pages= 231–370| doi= 10.1063/1.1416902| bibcode= 2002JPCRD..31..231G}} (Link added 4 August 2024)</ref> The pK_a of the hydroxyl group has been found, by means of ¹³C NMR spectroscopy, to be 14.4.<ref>{{cite journal| first1= Andre M. N.| last1= Silva

| first2= Xiaole| last2= Kong| first3 =Robert C.| last3=Hider| title= 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| journal= Biometals| year = 2009| volume= 22| issue= 5| pages= 771–778| doi= 10.1007/s10534-009-9224-5| pmid=19288211| s2cid= 11615864}}</ref>

The speciation diagram shows that solutions of citric acid are [[buffer solution]]s between about pH&nbsp;2 and pH&nbsp;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.<ref>{{cite web | url=http://openwetware.org/wiki/SSC | title=SSC - OpenWetWare }}</ref><ref>Maniatis, T.; Fritsch, E. F.; Sambrook, J. 1982. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.</ref> Tables compiled for biochemical studies are available.<ref>{{cite book | doi = 10.1016/0076-6879(55)01020-3 | chapter = [16] Preparation of buffers for use in enzyme studies

| title = Methods in Enzymology Volume 1 | year = 1955| last1 = Gomori| first1 = G.| isbn = 9780121818012| volume = 1| pages = 138–146 | chapter-url = https://static.igem.org/mediawiki/2008/8/84/Protein_Buffers.pdf | url = https://archive.org/details/methodsinenzymol01acad/page/138}}</ref>

Conversely, the pH of a 1&nbsp;mM solution of citric acid will be about 3.2. The pH of fruit juices from [[citrus fruit]]s like oranges and lemons depends on the citric acid concentration, with a higher concentration of citric acid resulting in a lower pH.

[[Acid salt]]s 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. The [[stability constants of complexes|stability constant]]s for the formation of these complexes are quite large because of the [[chelate 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 in [[ammonium ferric citrate]], {{chem2|[NH4+]5Fe(3+)(C6H4O7(4−))2*2H2O}}.<ref>{{cite journal| first1= M.| last1= Matzapetakis| first2= C. P. | last2= Raptopoulou| first3 =A. | last3=Tsohos| first4 =V. | last4=Papaefthymiou| first5 =S. N. | last5=Moon| first6 =A. | last6=Salifoglou| title= Synthesis, Spectroscopic and Structural Characterization of the First Mononuclear, Water Soluble Iron−Citrate Complex, (NH₄)₅Fe(C₆H₄O₇)₂·2H₂O| journal= J. Am. Chem. Soc.| year = 1998| volume= 120| issue= 50| pages= 13266–13267| doi= 10.1021/ja9807035}}</ref>

Citric acid can be [[ester]]ified at one or more of its three [[carboxylic acid]] groups to form any of a variety of mono-, di-, tri-, and mixed esters.<ref>{{cite journal |doi=10.1016/S0040-4020(96)01061-7|title=Total synthesis of rhizoferrin, an iron chelator|year=1997|last1=Bergeron|first1=Raymond J.|last2=Xin|first2=Meiguo|last3=Smith|first3=Richard E.|last4=Wollenweber|first4=Markus|last5=McManis|first5=James S.|last6=Ludin|first6=Christian|last7=Abboud|first7=Khalil A.|journal=Tetrahedron|volume=53|issue=2|pages=427–434}}</ref>

==Biochemistry==

===Citric acid cycle===

{{Main|Citric acid cycle}}

Citrate is an intermediate in the [[citric acid cycle]], also known as the TCA ('''T'''ri'''C'''arboxylic '''A'''cid) cycle or the Krebs cycle, a central metabolic pathway for animals, plants, and bacteria. [[Citrate synthase]] 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]]. 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 of [[Adenosine triphosphate]] (ATP). [[Hans Adolf Krebs]] received the 1953 [[Nobel Prize in Physiology or Medicine]] for the discovery.

===Other biological roles===

Citrate can be transported out of the [[mitochondria]] and into the cytoplasm, then broken down into [[acetyl-CoA]] for [[fatty acid synthesis]], and into oxaloacetate. Citrate is a positive modulator of this conversion, and [[allosterically]] regulates the enzyme [[acetyl-CoA carboxylase]], which is the regulating enzyme in the conversion of acetyl-CoA into [[malonyl-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 inhibit [[phosphofructokinase]], the catalyst of a rate-limiting step of [[glycolysis]]. 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 of [[Adenosine triphosphate|ATP]], another sign that there is no need to carry out glycolysis.<ref name="Tightly Controlled">{{cite book|last1=Stryer|first1=Lubert|last2=Berg|first2=Jeremy|last3=Tymoczko|first3=John|title=Biochemistry|date=2003|publisher=Freeman|location=New York|isbn=978-0716746843|edition=5. ed., international ed., 3. printing|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK22395/|chapter=Section 16.2: The Glycolytic Pathway Is Tightly Controlled}}</ref>

Citrate is a vital component of bone, helping to regulate the size of [[apatite]] crystals.<ref>{{cite journal|last1= Hu |first1= Y.-Y. |last2= Rawal |first2= A. |last3= Schmidt-Rohr |first3= K. |title= Strongly bound citrate stabilizes the apatite nanocrystals in bone |journal= Proceedings of the National Academy of Sciences |volume= 107 |pages= 22425–22429 |date=December 2010 |doi= 10.1073/pnas.1009219107 |pmid= 21127269 |pmc= 3012505 |issue=52|bibcode= 2010PNAS..10722425H |doi-access= free }}</ref>

==Applications==

===Food and drink===

{{Cookbook|Citric Acid}}[[File:Lemon pepper preparation.jpg|thumb|Powdered citric acid being used to prepare [[lemon 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.<ref name="ullmann" /> Within the [[European Union]] it is denoted by [[E number]] '''E330'''. Citrate salts of various metals are used to deliver those minerals in a biologically available form in many [[dietary supplement]]s. Citric acid has 247&nbsp;kcal per 100&nbsp;g.<ref name="FAOSouthgate">{{cite book |last1=Greenfield |first1=Heather |last2=Southgate |first2=D.A.T. |date=2003 |title=Food Composition Data: Production, Management and Use |location=Rome |publisher=[[FAO]] |page=146 |isbn=9789251049495 }}</ref> In the United States the purity requirements for citric acid as a food additive are defined by the [[Food Chemicals Codex]], which is published by the [[United 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 with [[sodium bicarbonate]] in a wide range of [[effervescence|effervescent]] formulae, both for ingestion (e.g., powders and tablets) and for personal care (''e.g.'', [[bath salts]], [[bath bomb]]s, and cleaning of [[Petroleum|grease]]). 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 in [[food coloring]] to balance the pH level of a normally basic dye.{{citation needed|date=October 2019}}

===Cleaning and chelating agent===

[[File:Fe2CITdianion.svg|thumb|144px|left|Structure of an iron(III) citrate complex<ref name="xiang">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}}</ref><ref name="shweky">{{cite journal|doi=10.1021/ic00101a001|title=Syntheses, Structures, and Magnetic Properties of Two Dinuclear Iron(III) Citrate Complexes|year=1994|last1=Shweky|first1=Itzhak|last2=Bino|first2=Avi|last3=Goldberg|first3=David P.|last4=Lippard|first4=Stephen J.|journal=Inorganic Chemistry|volume=33|issue=23|pages=5161–5162}}</ref>]]

Citric acid is an excellent [[chelation|chelating agent]], binding metals by making them soluble. It is used to remove and discourage the buildup of [[limescale]] from boilers and evaporators.<ref name="ullmann" /> It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. By chelating the metals in [[hard 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 successful [[eluant]] used for total ion-exchange separation of the [[lanthanide]]s, during the [[Manhattan Project]] in the 1940s.<ref>{{Cite journal|last1=JOHNSON|first1=WARREN C.|last2=QUILL|first2=LAURENCE L.|last3=DANIELS|first3=FARRINGTON|date=1947-09-01|title=Rare Earths Separation Developed on Manhattan Project|url=http://dx.doi.org/10.1021/cen-v025n035.p2494|journal=Chemical & Engineering News Archive|volume=25|issue=35|pages=2494|doi=10.1021/cen-v025n035.p2494|issn=0009-2347}}</ref> In the 1950s, it was replaced by the far more efficient<ref>{{Cite journal|date=2020-08-01|title=Individual and combined application of EDTA and citric acid assisted phytoextraction of copper using jute (Corchorus capsularis L.) seedlings|url=https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Individual+and+combined+application+of+EDTA+and+citric+acid+assisted+phytoextraction+of+copper+using+jute+%28Corchorus+capsularis+L.%29+seedlings&btnG= |journal=Environmental Technology & Innovation|volume=19|pages=100895|doi=10.1016/j.eti.2020.100895|issn=2352-1864|last1=Saleem|first1=Muhammad Hamzah|last2=Ali|first2=Shafaqat|last3=Rehman|first3=Muzammal|last4=Rizwan|first4=Muhammad|last5=Kamran|first5=Muhammad|last6=Mohamed|first6=Ibrahim A.A.|last7=Khan|first7=Zaid|last8=Bamagoos|first8=Atif A.|last9=Alharby|first9=Hesham F.|last10=Hakeem|first10=Khalid Rehman|last11=Liu|first11=Lijun|bibcode=2020EnvTI..1900895S |s2cid=219432688}}</ref> [[Ethylenediaminetetraacetic acid|EDTA]].

In industry, it is used to dissolve rust from steel, and to [[Passivation (chemistry)|passivate]] [[stainless steel]]s.<ref>{{Cite web|url=https://www.astm.org/Standards/A967.htm|title=ASTM A967 / A967M - 17 Standard Specification for Chemical Passivation Treatments for Stainless Steel Parts|website=www.astm.org}}</ref>

===Cosmetics, pharmaceuticals, dietary supplements, and foods===

Citric acid is used as an [[acidulant]] 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 an [[alpha hydroxy acid]] and is an active ingredient in chemical skin peels.<ref>{{Cite journal|last1=Tang|first1=Sheau-Chung|last2=Yang|first2=Jen-Hung|date=2018-04-10|title=Dual Effects of Alpha-Hydroxy Acids on the Skin|journal=Molecules |volume=23|issue=4|page=863|doi=10.3390/molecules23040863|issn=1420-3049|pmc=6017965|pmid=29642579|doi-access=free}}</ref>

Citric acid is commonly used as a buffer to increase the solubility of brown [[heroin]].<ref>{{cite journal |vauthors=Strang J, Keaney F, Butterworth G, Noble A, Best D |title=Different forms of heroin and their relationship to cook-up techniques: data on, and explanation of, use of lemon juice and other acids |journal=Subst Use Misuse |volume=36 |issue=5 |pages=573–88 |date=April 2001 |pmid=11419488 |doi=10.1081/ja-100103561 |s2cid=8516420 }}</ref>

Citric acid is used as one of the active ingredients in the production of facial tissues with antiviral properties.<ref>{{cite news | url = https://money.cnn.com/2004/07/14/news/fortune500/kleenex/ | title = Tissues that fight germs | publisher = CNN | date = July 14, 2004 | access-date =May 8, 2008}}</ref>

=== Other uses ===

The [[Buffering agent|buffering]] properties of citrates are used to control [[pH]] in household cleaners and [[pharmaceutical]]s.

Citric acid is used as an odorless alternative to [[white vinegar]] for fabric dyeing with [[acid dye]]s.

Sodium citrate is a component of [[Benedict's reagent]], used for both qualitative and quantitative identification of reducing sugars.<ref>{{Cite journal|last1=Chen|first1=Wei|last2=Abramowitz|first2=Matthew K.|date=February 2014|title=Treatment of Metabolic Acidosis in Patients With CKD|journal=American Journal of Kidney Diseases |volume=63|issue=2|pages=311–317|doi=10.1053/j.ajkd.2013.06.017|issn=0272-6386|pmc=3946919|pmid=23932089}}</ref>

Citric acid can be used as an alternative to nitric acid in [[passivation (chemistry)|passivation]] of [[stainless steel]].<ref>{{cite web|url=http://www.euro-inox.org/pdf/map/Passivating_Pickling_EN.pdf |title=Pickling and Passivating Stainless Steel |publisher=Euro-inox.org |access-date=2013-01-01 |url-status=dead |archive-url=https://web.archive.org/web/20120912054431/http://www.euro-inox.org/pdf/map/Passivating_Pickling_EN.pdf |archive-date=September 12, 2012 |df=mdy}}</ref>

Citric acid can be used as a lower-odor [[stop bath]] as part of the process for developing [[photographic film]]. [[Photographic developer]]s are alkaline, so a mild acid is used to neutralize and stop their action quickly, but commonly used [[acetic acid]] leaves a strong vinegar odor in the darkroom.<ref>{{cite web|last=Anchell |first=Steve |url=http://www.focalpress.com/books/details/9780240810553/ |title=The Darkroom Cookbook: 3rd Edition (Paperback) |publisher=Focal Press |access-date=2013-01-01}}</ref>

[[Citric acid/potassium-sodium citrate]] can be used as a blood acid regulator. The citric acid is included to improve palatability<ref>{{Cite web|last=PubChem|title=Sodium citrate|url=https://pubchem.ncbi.nlm.nih.gov/compound/6224|access-date=2021-08-02|website=pubchem.ncbi.nlm.nih.gov|language=en}}</ref>

Citric acid is an excellent [[soldering]] [[Flux (metallurgy)|flux]],<ref>{{cite web|url=https://apps.dtic.mil/dtic/tr/fulltext/u2/a295042.pdf |archive-url=https://web.archive.org/web/20200315161916/https://apps.dtic.mil/dtic/tr/fulltext/u2/a295042.pdf |url-status=dead |archive-date=March 15, 2020 |title=An Investigation of the Chemistry of Citric Acid in Military Soldering Applications |date=1995-06-19}}</ref> 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.<ref>{{Cite journal |last1=Berg |first1=C. |last2=Larsson |first2=L. |last3=Tiselius |first3=H. G. |date=1992 |title=The effects of a single evening dose of alkaline citrate on urine composition and calcium stone formation |url=https://pubmed.ncbi.nlm.nih.gov/1507355/ |journal=The Journal of Urology |volume=148 |issue=3 Pt 2 |pages=979–985 |doi=10.1016/s0022-5347(17)36795-2 |issn=0022-5347 |pmid=1507355}}</ref>

==Synthesis of other organic compounds==

Citric acid is a versatile precursor to many other organic compounds. Dehydration routes give [[itaconic acid]] and its anhydride.<ref>{{cite journal|author1=R. L. Shriner|author2=S. G. Ford|author3= l. J. Roll|journal=Org. Synth.|year=1931|volume=11|page=70|doi=10.15227/orgsyn.011.0070|title=Itaconic anhydride and itaconic acid}}</ref> [[Citraconic acid]] can be produced via thermal isomerization of itaconic acid anhydride.<ref>{{cite journal|author1=R. L. Shriner|author2=S. G. Ford|author3= l. J. Roll|journal=Org. Synth.|year=1931|volume=28|page=28|doi=10.15227/orgsyn.011.0028|title=Citraconic Anhydride and Citraconic Acid}}</ref> The required itaconic acid anhydride is obtained by dry distillation of citric acid. [[Aconitic acid]] can be synthesized by dehydration of citric acid using [[sulfuric acid]]:<ref>{{cite journal| author = Bruce, W. F. | title = Aconitic Acid | journal = Organic Syntheses | year = 1937 | volume = 17 | pages = 1|doi=10.15227/orgsyn.017.0001 }}</ref>

:(HO₂CCH₂)₂C(OH)CO₂H → HO₂CCH=C(CO₂H)CH₂CO₂H + H₂O

[[Acetonedicarboxylic acid]] can also be prepared by [[decarboxylation]] of citric acid in fuming sulfuric acid.<ref>{{OrgSynth | author = Roger Adams |author2=H. M. Chiles |author3=C. F. Rassweiler | title = Acetonedicarboxylic Acid | page = 5 | volume = 5 | year = 1925 | doi = 10.15227/orgsyn.005.0005}}</ref>

==Safety==

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.<ref name=ICSC>{{cite web | url = https://www.cdc.gov/niosh/ipcsneng/neng0855.html | work = International Chemical Safety Cards | title = Citric acid | publisher = [[NIOSH]] | date = 2018-09-18 | access-date = September 9, 2017 | archive-url = https://web.archive.org/web/20180712084742/https://www.cdc.gov/niosh/ipcsneng/neng0855.html | archive-date = July 12, 2018 | url-status = dead }}</ref> Long-term or repeated consumption may cause erosion of [[tooth enamel]].<ref name=ICSC/><ref>{{Cite journal | doi = 10.1016/j.triboint.2008.12.008 | journal = Tribology International | volume = 42 | issue = 11–12 | date = December 2009 | pages = 1558–1564 | title = Erosion behavior of human tooth enamel in citric acid solution |author=J. Zheng |author2=F. Xiao |author3=L. M. Qian |author4=Z. R. Zhou}}</ref><ref>{{Cite web | url = http://www.livestrong.com/article/147503-the-effect-of-citric-acid-on-tooth-enamel | title = Effect of Citric Acid on Tooth Enamel}}</ref>

==Compendial status==

* [[British Pharmacopoeia]]<ref name=ib29>{{cite web |last=British Pharmacopoeia Commission Secretariat |title=Index, BP 2009 |year=2009 |url=http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf |access-date=February 4, 2010 |url-status=dead |archive-url=https://web.archive.org/web/20090411071437/http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf |archive-date=April 11, 2009 |df=mdy}}</ref>

* [[Japanese Pharmacopoeia]]<ref name=jp15>{{cite web|title=Japanese Pharmacopoeia, Fifteenth Edition |year=2006 |url=http://jpdb.nihs.go.jp/jp15e/JP15.pdf |access-date=4 February 2010 |url-status=dead |archive-url=https://web.archive.org/web/20110722105441/http://jpdb.nihs.go.jp/jp15e/JP15.pdf |archive-date=July 22, 2011 |df=mdy}}</ref>

==See also==

*Closely related acids: [[isocitric acid]], [[aconitic acid]], and [[propane-1,2,3-tricarboxylic acid]] (tricarballylic acid, carballylic acid)

*[[Acids in wine]]

== Explanatory notes ==

{{Notelist|30em}}

==References==

{{Reflist|30em}}

== External links ==

{{Commons category|Citric acid}}

{{EB1911 poster|Citric Acid}}

{{Digestives}}

{{citrus}}

{{Authority control}}

[[Category:Citrates| ]]

[[Category:Alpha hydroxy acids]]

[[Category:Chelating agents]]

[[Category:Citrus]]

[[Category:Condiments]] <!-- usually called "sour salt" -->

[[Category:E-number additives]]

[[Category:Food acidity regulators]]

[[Category:Household chemicals]]

[[Category:Photographic chemicals]]

[[Category:Tricarboxylic acids]]