Editing Lactic acid

{{Short description|Organic acid}}
{{Use dmy dates|date=July 2018}}
{{chembox
|Verifiedfields = 
|Watchedfields = changed
|verifiedrevid = 477002503
|Name = Lactic acid
|ImageFileL1 = Lactic-acid-skeletal.svg
|ImageSizeL1 = 130
|ImageFileR1 = Lactic-acid-from-xtal-3D-bs-17.png
|ImageSizeR1 = 130
|ImageCaption2 = {{sc|L}}-Lactic acid
|PIN = 2-Hydroxypropanoic acid<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 748 | doi = 10.1039/9781849733069-00648 | isbn = 978-0-85404-182-4| chapter = CHAPTER P-6. Applications to Specific Classes of Compounds }}</ref>
|OtherNames = {{ubl|Lactic acid<ref name=iupac2013 />|Milk acid}}
|Section1 = {{Chembox Identifiers
|IUPHAR_ligand = 2932
|3DMet = B01180
|Beilstein = 1720251
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo = 50-21-5
|CASNo1_Ref = {{cascite|correct|CAS}}
|CASNo1 = 79-33-4
|CASNo1_Comment = ({{sc|L}})
|CASNo2_Ref = {{cascite|correct|CAS}}
|CASNo2 = 10326-41-7
|CASNo2_Comment = ({{sc|D}})
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 330546
|EC_number = 200-018-0
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 3B8D35Y7S4
|UNII1_Ref = {{fdacite|correct|FDA}}
|UNII1 = F9S9FFU82N
|UNII1_Comment = ({{sc|L}})
|UNII2_Ref = {{fdacite|correct|FDA}}
|UNII2 = 3Q6M5SET7W
|UNII2_Comment = ({{sc|D}})
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 422
|KEGG = D00111
|KEGG1 = C00186
|KEGG2 = C00256
|Gmelin = 362717
|RTECS = OD2800000
|UNNumber = 3265
|PubChem = 612
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C3H6O3/c1-2(4)3(5)6/h2,4H,1H3,(H,5,6)/t2-/m0/s1
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = JVTAAEKCZFNVCJ-REOHCLBHSA-N
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 96860
|SMILES = CC(O)C(=O)O
}}
|Section2 = {{Chembox Properties
|C=3 | H=6 | O=3
|Solubility=Miscible<ref name=GESTIS>{{GESTIS|ZVG=13000}}</ref>
|MeltingPtC =18
|BoilingPtC = 122
|BoilingPt_notes = at 15{{nbsp}}mmHg
|pKa = 3.86,<ref>{{cite book| vauthors = Dawson RM |display-authors=etal|title=Data for Biochemical Research|location=Oxford|publisher=Clarendon Press|date=1959}}</ref> 15.1<ref>{{cite journal | vauthors = Silva AM, Kong X, Hider RC |title = Determination of the pKa value of the hydroxyl group in the alpha-hydroxycarboxylates citrate, malate and lactate by 13C NMR: implications for metal coordination in biological systems | journal = Biometals | volume = 22 | issue = 5 | pages = 771–8 | date = October 2009 | pmid = 19288211 | doi = 10.1007/s10534-009-9224-5 | s2cid = 11615864 }}</ref>
}}
|Section3 = {{Chembox Thermochemistry| DeltaHc = 1361.9{{nbsp}}kJ/mol, 325.5{{nbsp}}kcal/mol, 15.1{{nbsp}}kJ/g, 3.61{{nbsp}}kcal/g}}
|Section4 = {{Chembox Related
|OtherAnions = Lactate
|OtherFunction_label = [[carboxylic acid]]s
|OtherFunction = {{ubl|[[Acetic acid]]|[[Glycolic acid]]|[[Propionic acid]]|[[3-Hydroxypropanoic acid]]|[[Malonic acid]]|[[Butyric acid]]|[[Hydroxybutyric acid]]}}
|OtherCompounds = {{ubl|[[1-Propanol]]|[[2-Propanol]]|[[Propionaldehyde]]|[[Acrolein]]|[[Sodium lactate]]|[[Ethyl lactate]]}}
}}
|Section5 = {{Chembox Pharmacology
|ATCCode_prefix = G01
|ATCCode_suffix = AD01
|ATC_Supplemental = {{ATCvet|P53|AG02}}
}}
|Section6 = {{Chembox Hazards
|GHSPictograms = {{GHS05}}<ref name="sigma">{{Sigma-Aldrich|sial|id=69785|name={{small|DL}}-Lactic acid|access-date=20 July 2013}}</ref>
|HPhrases = {{H-phrases|315|318}}<ref name="sigma" />
|PPhrases = {{P-phrases|280|305+351+338}}<ref name="sigma" />
}}
}}

'''Lactic acid''' is an [[organic acid]]. It has the molecular formula '''C<sub>3</sub>H<sub>6</sub>O<sub>3</sub>'''. It is white in the solid state and it is [[miscibility|miscible]] with water.<ref name=GESTIS/> When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natural sources. Lactic acid is an [[alpha-hydroxy acid]] (AHA) due to the presence of a [[hydroxyl]] group adjacent to the [[carboxyl]] group. It is used as a synthetic intermediate in many [[organic synthesis]] industries and in various [[biochemical]] industries. The [[conjugate base]] of lactic acid is called '''lactate''' (or the lactate anion). The name of the derived [[acyl group]] is '''lactoyl'''.

In solution, it can ionize by a loss of a proton to produce the lactate [[ion]] {{chem|CH|3|CH(OH)CO|2|−}}. Compared to [[acetic acid]], its [[Acid dissociation constant|p''K''{{sub|a}}]] is 1 unit less, meaning lactic acid is ten times more acidic than acetic acid. This higher acidity is the consequence of the intramolecular hydrogen bonding between the α-hydroxyl and the carboxylate group.

Lactic acid is [[chirality (chemistry)|chiral]], consisting of two [[enantiomer]]s. One is known as {{sc|L}}-lactic acid, (''S'')-lactic acid, or (+)-lactic acid, and the other, its mirror image, is {{sc|D}}-lactic acid, (''R'')-lactic acid, or (−)-lactic acid. A mixture of the two in equal amounts is called {{sc|DL}}-lactic acid, or [[racemic]] lactic acid. Lactic acid is [[hygroscopy|hygroscopic]]. {{sc|DL}}-Lactic acid is [[miscible]] with water and with ethanol above its melting point, which is about {{cvt|16 to 18|C}}. {{sc|D}}-Lactic acid and {{sc|L}}-lactic acid have a higher melting point. Lactic acid produced by fermentation of milk is often racemic, although certain species of bacteria produce solely {{sc|D}}-lactic acid.<ref>{{Cite web |title=(S)-lactic acid (CHEBI:422) |url=https://www.ebi.ac.uk/chebi/searchId.do?printerFriendlyView=true&locale=null&chebiId=422&viewTermLineage=null&structureView=& |access-date=2024-01-05 |website=www.ebi.ac.uk}}</ref> On the other hand, lactic acid produced by fermentation in animal muscles has the ({{sc|L}}) enantiomer and is sometimes called "sarcolactic" acid, from the Greek {{transliteration|grc|sarx}}, meaning "flesh".

In animals, {{sc|L}}-lactate is constantly produced from [[pyruvate]] via the [[enzyme]] [[lactate dehydrogenase]] (LDH) in a process of [[fermentation (biochemistry)|fermentation]] during normal [[metabolism]] and [[exercise]].<ref name="Skeletal muscle PGC-1α controls who">{{cite journal | vauthors = Summermatter S, Santos G, Pérez-Schindler J, Handschin C | title = Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 21 | pages = 8738–43 | date = May 2013 | pmid = 23650363 | pmc = 3666691 | doi = 10.1073/pnas.1212976110 | bibcode = 2013PNAS..110.8738S | doi-access = free }}</ref> It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal, which is governed by a number of factors, including [[monocarboxylate transporter]]s, concentration and isoform of LDH, and oxidative capacity of tissues.<ref name="Skeletal muscle PGC-1α controls who"/> The concentration of [[blood]] lactate is usually {{nowrap|1–2}}{{nbsp}}{{abbrlink|mM|millimolar}} at rest, but can rise to over 20{{nbsp}}mM during intense exertion and as high as 25{{nbsp}}mM afterward.<ref name="LA-UCD">{{cite web | url=http://www.ucdmc.ucdavis.edu/sportsmedicine/resources/lactate_description.html | title=Lactate Profile | publisher=UC Davis Health System, Sports Medicine and Sports Performance | access-date=23 November 2015}}</ref><ref>{{cite journal | vauthors = Goodwin ML, Harris JE, Hernández A, Gladden LB | title = Blood lactate measurements and analysis during exercise: a guide for clinicians | journal = Journal of Diabetes Science and Technology | volume = 1 | issue = 4 | pages = 558–69 | date = July 2007 | pmid = 19885119 | pmc = 2769631 | doi = 10.1177/193229680700100414 }}</ref> In addition to other biological roles, {{sc|L}}-lactic acid is the primary [[endogenous]] [[agonist]] of [[hydroxycarboxylic acid receptor 1]] (HCA{{sub|1}}), which is a {{nowrap|[[Gi alpha subunit|G{{sub|i/o}}-coupled]]}} [[G protein-coupled receptor]] (GPCR).<ref name="IUPHAR's comprehensive 2011 review on HCARs">{{cite journal | vauthors = Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP | title = International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B) | journal = Pharmacological Reviews | volume = 63 | issue = 2 | pages = 269–90 | date = June 2011 | pmid = 21454438 | doi = 10.1124/pr.110.003301 | doi-access = free }}</ref><ref name="IUPHAR-DB HCAR family page">{{cite web | vauthors = Offermanns S, Colletti SL, IJzerman AP, Lovenberg TW, Semple G, Wise A, Waters MG |title=Hydroxycarboxylic acid receptors |url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=48 |website=IUPHAR/BPS Guide to Pharmacology |publisher=International Union of Basic and Clinical Pharmacology |access-date=13 July 2018}}</ref>

In industry, [[lactic acid fermentation]] is performed by [[lactic acid bacteria]], which convert simple [[carbohydrates]] such as [[glucose]], [[sucrose]], or [[galactose]] to lactic acid. These bacteria can also grow in the [[mouth]]; the [[acid]] they produce is responsible for the [[tooth]] decay known as [[Tooth decay|cavities]].<ref>{{cite journal | vauthors = Badet C, Thebaud NB | title = Ecology of lactobacilli in the oral cavity: a review of literature | journal = The Open Microbiology Journal | volume = 2 | pages = 38–48 | year = 2008 | pmid = 19088910 | pmc = 2593047 | doi =  10.2174/1874285800802010038  |doi-access=free}}</ref><ref>{{cite journal | vauthors = Nascimento MM, Gordan VV, Garvan CW, Browngardt CM, Burne RA | title = Correlations of oral bacterial arginine and urea catabolism with caries experience | journal = Oral Microbiology and Immunology | volume = 24 | issue = 2 | pages = 89–95 | date = April 2009 | pmid = 19239634 | pmc = 2742966 | doi = 10.1111/j.1399-302X.2008.00477.x }}</ref><ref>{{cite journal | vauthors = Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I, Dewhirst FE, Leys EJ, Paster BJ | title = Bacteria of dental caries in primary and permanent teeth in children and young adults | journal = Journal of Clinical Microbiology | volume = 46 | issue = 4 | pages = 1407–17 | date = April 2008 | pmid = 18216213 | pmc = 2292933 | doi = 10.1128/JCM.01410-07 }}</ref><ref>{{cite journal | vauthors = Caufield PW, Li Y, Dasanayake A, Saxena D | title = Diversity of lactobacilli in the oral cavities of young women with dental caries | journal = Caries Research | volume = 41 | issue = 1 | pages = 2–8 | year = 2007 | pmid = 17167253 | pmc = 2646165 | doi = 10.1159/000096099 }}</ref> In [[medicine]], lactate is one of the main components of [[lactated Ringer's solution]] and [[Hartmann's solution]]. These [[intravenous]] fluids consist of [[sodium]] and [[potassium]] [[cation]]s along with lactate and [[chloride]] [[anion]]s in solution with distilled [[water]], generally in concentrations [[isotonicity|isotonic]] with [[human]] [[blood]]. It is most commonly used for fluid [[resuscitation]] after blood loss due to [[physical trauma|trauma]], [[surgery]], or [[burn (injury)|burns]].

Lactic acid is produced in human tissues when the demand for oxygen is limited by the supply. This occurs during tissue [[ischemia]] when the flow of blood is limited as in sepsis or hemorrhagic shock. It may also occur when demand for oxygen is high such as with intense exercise. The process of [[lactic acidosis]] produces lactic acid which results in an [[wikt:oxygen debt|oxygen debt]] which can be resolved or repaid when tissue oxygenation improves.<ref>{{Cite journal |last1=Achanti |first1=Anand |last2=Szerlip |first2=Harold M. |date=1 January 2023 |title=Acid-Base Disorders in the Critically Ill Patient |journal=Clin J Am Soc Nephrol |language=en |volume=18 |issue=1 |pages=102–112 |doi=10.2215/CJN.04500422 |issn=1555-9041 |pmc=10101555 |pmid=35998977}}</ref>

==History==
Swedish chemist [[Carl Wilhelm Scheele]] was the first person to isolate lactic acid in 1780 from sour [[milk]].<ref name="Parks">{{cite journal|doi=10.1146/annurev-cancerbio-030419-033556|title=Lactate and Acidity in the Cancer Microenvironment|year=2020|last1=Parks|first1=Scott K.|last2=Mueller-Klieser|first2=Wolfgang|last3=Pouysségur|first3=Jacques|journal=Annual Review of Cancer Biology|volume=4|pages=141–158|doi-access=free}}</ref> The name reflects the ''[[wikt:lact-#Prefix|lact-]]'' combining form derived from the Latin word {{lang|la|[[wikt:lac#Latin|lac]]}}, meaning "milk". In 1808, [[Jöns Jacob Berzelius]] discovered that lactic acid (actually {{sc|L}}-lactate) is also produced in [[muscle]]s during exertion.<ref>{{Cite web|last=Roth|first=Stephen M. | name-list-style = vanc |title=Why does lactic acid build up in muscles? And why does it cause soreness?|website=[[Scientific American]] |url=https://www.scientificamerican.com/article/why-does-lactic-acid-buil/|access-date=23 January 2006}}</ref> Its structure was established by [[Johannes Wislicenus]] in 1873.

In 1856, the role of ''[[Lactobacillus]]'' in the synthesis of lactic acid was discovered by [[Louis Pasteur]]. This pathway was used commercially by the German [[pharmacy]] [[Boehringer Ingelheim]] in 1895.{{cn|date=May 2024}}

In 2006, global production of lactic acid reached 275,000 tonnes with an average annual growth of 10%.<ref>{{cite web|url=http://www.nnfcc.co.uk/publications/nnfcc-renewable-chemicals-factsheet-lactic-acid|title=NNFCC Renewable Chemicals Factsheet: Lactic Acid|publisher=NNFCC}}</ref>

==Production==
Lactic acid is produced industrially by bacterial [[fermentation]] of [[carbohydrate]]s, or by chemical synthesis from [[acetaldehyde]].<ref name=benn>H. Benninga (1990): "A History of Lactic Acid Making: A Chapter in the History of Biotechnology". Volume 11 of ''Chemists and Chemistry''.  Springer, {{ISBN|0792306252}}, 9780792306252</ref> {{As of|2009}}, lactic acid was produced predominantly (70–90%)<ref>{{Cite book|title=Technische Biopolymere|last=Endres|first=Hans-Josef | name-list-style = vanc |publisher=Hanser-Verlag|year=2009|isbn=978-3-446-41683-3|location=München|pages=103}}</ref> by fermentation. Production of racemic lactic acid consisting of a 1:1 mixture of {{sc|D}} and {{sc|L}} stereoisomers, or of mixtures with up to 99.9% {{sc|L}}-lactic acid, is possible by microbial fermentation. Industrial scale production of {{sc|D}}-lactic acid by fermentation is possible, but much more challenging.{{cn|date=May 2024}}

===Fermentative production===
[[Fermented milk products]] are obtained industrially by fermentation of [[milk]] or [[whey]] by ''Lactobacillus'' bacteria: ''[[Lactobacillus acidophilus]]'', ''[[Lacticaseibacillus casei]]'' (''Lactobacillus casei''), [[Lactobacillus delbrueckii subsp. bulgaricus|''Lactobacillus delbrueckii'' subsp. ''bulgaricus'']] (''Lactobacillus bulgaricus''), ''[[Lactobacillus helveticus]]'', ''[[Lactococcus lactis]]'' ,'' [[Bacillus amyloliquefaciens]]'', and [[Streptococcus salivarius subsp. thermophilus|''Streptococcus salivarius'' subsp. ''thermophilus'']] (''Streptococcus thermophilus'').{{cn|date=May 2024}}

As a starting material for industrial production of lactic acid, almost any carbohydrate source containing {{chem|link=Pentose|C|5}} (Pentose sugar) and {{chem|link=Hexose|C|6}} (Hexose sugar) can be used. Pure sucrose, glucose from starch, raw sugar, and beet juice are frequently used.<ref>{{cite book|last1=Groot|first1=Wim|last2=van Krieken|first2=Jan|last3=Slekersl|first3=Olav|last4=de Vos|first4=Sicco|editor1-last=Auras|editor1-first=Rafael|editor2-last=Lim|editor2-first=Long-Tak|editor3-last=Selke|editor3-first=Susan E. M.|editor4-last=Tsuji|editor4-first=Hideto | name-list-style = vanc |contribution=Chemistry and production of lactic acid, lactide and poly(lactic acid) |title=Poly(Lactic acid)|publisher=Wiley|location=Hoboken|isbn=978-0-470-29366-9|page=3|date=2010-10-19}}</ref> Lactic acid producing bacteria can be divided in two classes: homofermentative bacteria like ''Lactobacillus casei'' and ''Lactococcus lactis'', producing two moles of lactate from one mole of glucose, and heterofermentative species producing one mole of lactate from one mole of glucose as well as [[carbon dioxide]] and [[acetic acid]]/[[ethanol]].<ref>{{cite book|last1=König|first1=Helmut|last2=Fröhlich|first2=Jürgen | name-list-style = vanc |title=Lactic acid bacteria in Biology of Microorganisms on Grapes, in Must and in Wine|date=2009|publisher=Springer-Verlag|isbn=978-3-540-85462-3|page=3}}</ref>

===Chemical production===
Racemic lactic acid is synthesized industrially by reacting [[acetaldehyde]] with [[hydrogen cyanide]] and hydrolysing the resultant [[lactonitrile]]. When [[hydrolysis]] is performed by [[hydrochloric acid]], [[ammonium chloride]] forms as a by-product; the Japanese company Musashino is one of the last big manufacturers of lactic acid by this route.<ref>{{Ullmann|last1=Westhoff|first1=Gerrit|last2=Starr|first2=John N.| title=Lactic Acids|year=2012|doi=10.1002/14356007.a15_097.pub3|isbn=9783527306732}}</ref> Synthesis of both racemic and enantiopure lactic acids is also possible from other starting materials ([[vinyl acetate]], [[glycerol]], etc.) by application of catalytic procedures.<ref>{{cite journal|last1=Shuklov|first1=Ivan A.|last2=Dubrovina|first2=Natalia V.|last3=Kühlein|first3=Klaus|last4=Börner|first4=Armin | name-list-style = vanc |title=Chemo-Catalyzed Pathways to Lactic Acid and Lactates|journal=Advanced Synthesis and Catalysis|date=2016|volume=358|issue=24|pages=3910–3931|doi=10.1002/adsc.201600768}}</ref>

==Biology==
===Molecular biology===
{{sc|L}}-Lactic acid is the primary [[endogenous]] [[agonist]] of [[hydroxycarboxylic acid receptor&nbsp;1]] (HCA<sub>1</sub>), a {{nowrap|[[Gi alpha subunit|G<sub>i/o</sub>-coupled]]}} [[G protein-coupled receptor]] (GPCR).<ref name="IUPHAR's comprehensive 2011 review on HCARs" /><ref name="IUPHAR-DB HCAR family page" />

===Metabolism and exercise===
{{See also|N-Lactoylphenylalanine}}
During power exercises such as [[sprint (running)|sprinting]], when the rate of demand for energy is high, [[glucose]] is broken down and oxidized to [[pyruvate]], and lactate is then produced from the pyruvate faster than the body can process it, causing lactate concentrations to rise. The production of lactate is beneficial for [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]] regeneration (pyruvate is reduced to lactate while NADH is oxidized to NAD<sup>+</sup>), which is used up in oxidation of [[glyceraldehyde 3-phosphate]] during production of pyruvate from glucose, and this ensures that energy production is maintained and exercise can continue. During intense exercise, the respiratory chain cannot keep up with the amount of hydrogen ions that join to form NADH, and cannot regenerate NAD<sup>+</sup> quickly enough, so pyruvate is converted to lactate to allow energy production by [[glycolysis]] to continue.<ref name="Ferguson 2018">{{cite journal | last1=Ferguson | first1=Brian S. | last2=Rogatzki | first2=Matthew J. | last3=Goodwin | first3=Matthew L. | last4=Kane | first4=Daniel A. | last5=Rightmire | first5=Zachary | last6=Gladden | first6=L. Bruce | title=Lactate metabolism: historical context, prior misinterpretations, and current understanding | journal=European Journal of Applied Physiology | volume=118 | date=2018 | issue=4 | issn=1439-6319 | doi=10.1007/s00421-017-3795-6 | pages=691–728| pmid=29322250 }}</ref>

The resulting lactate can be used in two ways:
* [[Oxidation]] back to [[pyruvate]] by well-oxygenated [[muscle]] cells, heart cells, and brain cells
** Pyruvate is then directly used to fuel the [[Krebs cycle]]
* Conversion to [[glucose]] via [[gluconeogenesis]] in the liver and release back into circulation by means of the [[Cori cycle]]<ref name=mcardlekatch>{{Cite book|vauthors=McArdle WD, Katch FI, Katch VL|title=Exercise Physiology: Energy, Nutrition, and Human Performance|year=2010|publisher=Wolters Kluwer/Lippincott Williams & Wilkins Health|isbn=978-0-683-05731-7|url-access=registration|url=https://archive.org/details/exercisephysiolo00mcar_0}}</ref>
** If blood glucose concentrations are high, the glucose can be used to build up the liver's [[glycogen]] stores.

Lactate is continually formed at rest and during all exercise intensities. Lactate serves as a metabolic fuel being produced and oxidatively disposed in resting and exercising muscle and other tissues.<ref name="Ferguson 2018" /> Some sources of excess lactate production are metabolism in [[red blood cell]]s, which lack [[mitochondria]] that perform aerobic respiration, and limitations in the rates of enzyme activity in muscle fibers during intense exertion.<ref name=mcardlekatch/> [[Lactic acidosis]] is a [[physiology|physiological condition]] characterized by accumulation of lactate (especially {{sc|L}}-lactate), with formation of an excessively high proton concentration [H<sup>+</sup>] and correspondingly low [[pH]] in the tissues, a form of [[metabolic acidosis]].<ref name="Ferguson 2018" />

The first stage in metabolizing glucose is [[glycolysis]], the conversion of glucose to pyruvate<sup>−</sup> and H<sup>+</sup>:

:{{chem2|C6H12O6 + 2 NAD+ + 2 ADP(3-) + 2 HPO4(2-) -> 2 CH3COCO2- + 2 H+ + 2 NADH + 2 ATP(4-) + 2 H2O}}

When sufficient oxygen is present for aerobic respiration, the pyruvate is oxidized to {{chem2|CO2}} and water by the Krebs cycle, in which [[oxidative phosphorylation]] generates ATP for use in powering the cell.
When insufficient oxygen is present, or when there is insufficient capacity for pyruvate oxidation to keep up with rapid pyruvate production during intense exertion, the pyruvate is converted to lactate<sup>−</sup> by [[lactate dehydrogenase]]), a process that absorbs these protons:<ref name=Robergs>{{cite journal | vauthors = Robergs RA, Ghiasvand F, Parker D | title = Biochemistry of exercise-induced metabolic acidosis | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 287 | issue = 3 | pages = R502–R516 | date = September 2004 | pmid = 15308499 | doi = 10.1152/ajpregu.00114.2004 | s2cid = 2745168 }}</ref>

:{{chem2|2 CH3COCO2- + 2 H+ + 2 NADH -> 2 CH3CH(OH)CO2- + 2 NAD+}}

The combined effect is:

:{{chem2|C6H12O6 + 2 ADP(3-) + 2HPO4(2-) -> 2 CH3CH(OH)CO2- + 2 ATP(4-) + 2 H2O}}

The production of lactate from glucose ({{chem2|glucose → 2 lactate- + 2 H+}}), when viewed in isolation, releases two H<sup>+</sup>. The H<sup>+</sup> are absorbed in the production of ATP, but H<sup>+</sup> is subsequently released during hydrolysis of ATP:

:{{chem2|ATP(4−) + H2O → ADP(3-) + HPO4(2-) + H+}}

Once the production and use of ATP is included, the overall reaction is

:{{chem2|C6H12O6 -> 2 CH3CH(OH)CO2- + 2 H+}}

The resulting increase in acidity persists until the excess lactate and protons are converted back to pyruvate, and then to glucose for later use, or to {{chem2|CO2}} and water for the production of ATP.<ref name="Ferguson 2018" />

=== Neural tissue energy source ===
Although [[glucose]] is usually assumed to be the main energy source for living tissues, there is evidence that lactate, in preference to  glucose, is preferentially metabolized by [[neuron]]s in the [[brain]]s of several [[mammalian]] species that include [[mouse|mice]], [[rat]]s, and [[human]]s.<ref name=zilberter2010/><ref>{{cite journal | vauthors = Wyss MT, Jolivet R, Buck A, Magistretti PJ, Weber B | title = In vivo evidence for lactate as a neuronal energy source | journal = The Journal of Neuroscience | volume = 31 | issue = 20 | pages = 7477–85 | date = May 2011 | pmid = 21593331 | pmc = 6622597 | doi = 10.1523/JNEUROSCI.0415-11.2011 | url = http://www.zora.uzh.ch/55080/1/Wyss_Weber_J_Neuroscience%282011%29.pdf }}</ref><ref name="Ferguson 2018" />  According to the [[lactate shuttle|lactate-shuttle hypothesis]], [[glia]]l cells are responsible for transforming glucose into lactate, and for providing lactate to the neurons.<ref>{{cite journal | vauthors = Gladden LB | title = Lactate metabolism: a new paradigm for the third millennium | journal = The Journal of Physiology | volume = 558 | issue = Pt 1 | pages = 5–30 | date = July 2004 | pmid = 15131240 | pmc = 1664920 | doi = 10.1113/jphysiol.2003.058701 }}</ref><ref>{{cite journal | vauthors = Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ | title = Activity-dependent regulation of energy metabolism by astrocytes: an update | journal = Glia | volume = 55 | issue = 12 | pages = 1251–62 | date = September 2007 | pmid = 17659524 | doi = 10.1002/glia.20528 | s2cid = 18780083 }}</ref> Because of this local metabolic activity of glial cells, the [[extracellular fluid]] immediately surrounding neurons strongly differs in composition from the [[blood]] or [[cerebrospinal fluid]], being much richer with lactate, as was found in [[microdialysis]] studies.<ref name=zilberter2010>{{cite journal | vauthors = Zilberter Y, Zilberter T, Bregestovski P | title = Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis | journal = Trends in Pharmacological Sciences | volume = 31 | issue = 9 | pages = 394–401 | date = September 2010 | pmid = 20633934 | doi = 10.1016/j.tips.2010.06.005 }}</ref>

=== Brain development metabolism ===
Some evidence suggests that lactate is important at early stages of development for brain metabolism in [[prenatal]] and early [[postnatal]] subjects, with lactate at these stages having higher concentrations in body liquids, and being utilized by the brain preferentially over glucose.<ref name=zilberter2010/> It was also hypothesized that lactate may exert a strong action over [[GABA]]ergic networks in the [[brain development|developing brain]], making them more [[inhibitory]] than it was previously assumed,<ref>{{cite journal | vauthors = Holmgren CD, Mukhtarov M, Malkov AE, Popova IY, Bregestovski P, Zilberter Y | title = Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro | journal = Journal of Neurochemistry | volume = 112 | issue = 4 | pages = 900–12 | date = February 2010 | pmid = 19943846 | doi = 10.1111/j.1471-4159.2009.06506.x | s2cid = 205621542 | doi-access = free }}</ref> acting either through better support of metabolites,<ref name=zilberter2010/> or alterations in base intracellular [[pH]] levels,<ref>{{cite journal | vauthors = Tyzio R, Allene C, Nardou R, Picardo MA, Yamamoto S, Sivakumaran S, Caiati MD, Rheims S, Minlebaev M, Milh M, Ferré P, Khazipov R, Romette JL, Lorquin J, Cossart R, Khalilov I, Nehlig A, Cherubini E, Ben-Ari Y | title = Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate | journal = The Journal of Neuroscience | volume = 31 | issue = 1 | pages = 34–45 | date = January 2011 | pmid = 21209187 | pmc = 6622726 | doi = 10.1523/JNEUROSCI.3314-10.2011 }}</ref><ref>{{cite journal | vauthors = Ruusuvuori E, Kirilkin I, Pandya N, Kaila K | title = Spontaneous network events driven by depolarizing GABA action in neonatal hippocampal slices are not attributable to deficient mitochondrial energy metabolism | journal = The Journal of Neuroscience | volume = 30 | issue = 46 | pages = 15638–42 | date = November 2010 | pmid = 21084619 | pmc = 6633692 | doi = 10.1523/JNEUROSCI.3355-10.2010 }}</ref> or both.<ref>{{cite journal | vauthors = Khakhalin AS | title = Questioning the depolarizing effects of GABA during early brain development | journal = Journal of Neurophysiology | volume = 106 | issue = 3 | pages = 1065–7 | date = September 2011 | pmid = 21593390 | doi = 10.1152/jn.00293.2011 | s2cid = 13966338 }}</ref>

Studies of brain slices of mice show that [[beta-hydroxybutyrate|β-hydroxybutyrate]], lactate, and pyruvate act as oxidative energy substrates, causing an increase in the NAD(P)H oxidation phase, that glucose was insufficient as an energy carrier during intense synaptic activity and, finally, that lactate can be an efficient energy substrate capable of sustaining and enhancing brain aerobic energy metabolism ''in vitro''.<ref>{{cite journal | vauthors = Ivanov A, Mukhtarov M, Bregestovski P, Zilberter Y | title = Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices | journal = Frontiers in Neuroenergetics | volume = 3 | pages = 2 | year = 2011 | pmid = 21602909 | pmc = 3092068 | doi = 10.3389/fnene.2011.00002 | doi-access = free }}</ref> The study "provides novel data on biphasic NAD(P)H fluorescence transients, an important physiological response to neural activation that has been reproduced in many studies and that is believed to originate predominantly from activity-induced concentration changes to the cellular NADH pools."<ref>{{cite journal | vauthors = Kasischke K | title = Lactate fuels the neonatal brain | journal = Frontiers in Neuroenergetics | volume = 3 | pages = 4 | year = 2011 | pmid = 21687795 | pmc = 3108381 | doi = 10.3389/fnene.2011.00004 | doi-access = free }}</ref>

Lactate can also serve as an important source of energy for other organs, including the heart and liver. During physical activity, up to 60% of the heart muscle's energy turnover rate derives from lactate oxidation.<ref name="Parks"/>

==Blood testing==
[[File:Blood values sorted by mass and molar concentration.png|thumb|450px|[[Reference ranges for blood tests]], comparing lactate content (shown in violet at center-right) to other constituents in human blood]]
[[Blood test]]s for lactate are performed to determine the status of the [[acid base homeostasis]] in the body. [[Blood sampling]] for this purpose is often [[arterial blood sampling|arterial]] (even if it is more difficult than [[venipuncture]]), because lactate levels differ substantially between arterial and venous, and the arterial level is more representative for this purpose.

{| class="wikitable"
|+ Reference ranges
|-
!
!Lower limit
!Upper limit
!Unit
|-
! rowspan =2| Venous
| 4.5<ref name=bloodbook>[http://www.bloodbook.com/ranges.html Blood Test Results – Normal Ranges] {{Webarchive|url=https://web.archive.org/web/20121102092931/http://www.bloodbook.com/ranges.html |date=2 November 2012 }} Bloodbook.Com</ref> || 19.8<ref name=bloodbook/> || mg/dL
 |-
| 0.5<ref name=lactate-mass>Derived from mass values using molar mass of 90.08 g/mol</ref> || 2.2<ref name=lactate-mass/> || mmol/L
 |-
! rowspan =2| Arterial
| 4.5<ref name=bloodbook/> || 14.4<ref name=bloodbook/> || mg/dL
 |-
| 0.5<ref name="lactate-mass"/> || 1.6<ref name=lactate-mass/> || mmol/L
 |}

During [[childbirth]], lactate levels in the fetus can be quantified by [[fetal scalp blood testing]].

== Uses ==
=== Polymer precursor ===
{{Main article|polylactic acid}}
Two molecules of lactic acid can be dehydrated to the [[lactone]] [[lactide]].  In the presence of [[catalysts]] lactide polymerize to either atactic or [[syndiotactic]] [[polylactic acid|polylactide]] (PLA), which are [[biodegradable]] [[polyester]]s. PLA is an example of a plastic that is not derived from [[petrochemical]]s.

=== Pharmaceutical and cosmetic applications ===
Lactic acid is also employed in [[pharmaceutical technology]] to produce water-soluble lactates from otherwise-insoluble active ingredients. It finds further use in topical preparations and [[cosmetics]] to adjust acidity and for its [[disinfectant]] and [[keratolytic]] properties.

Lactic acid containing bacteria have shown promise in reducing [[oxaluria]] with its descaling properties on calcium compounds.<ref>{{Cite journal |last1=Campieri |first1=C. |last2=Campieri |first2=M. |last3=Bertuzzi |first3=V. |last4=Swennen |first4=E. |last5=Matteuzzi |first5=D. |last6=Stefoni |first6=S. |last7=Pirovano |first7=F. |last8=Centi |first8=C. |last9=Ulisse |first9=S. |last10=Famularo |first10=G. |last11=De Simone |first11=C. |date=September 2001 |title=Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration |journal=Kidney International |volume=60 |issue=3 |pages=1097–1105 |doi=10.1046/j.1523-1755.2001.0600031097.x |issn=0085-2538 |pmid=11532105|doi-access=free }}</ref>

=== Foods ===
==== Fermented food ====
{{main|Lactic acid fermentation#Applications}}
Lactic acid is found in many fermented foods.
* Sour [[milk]] products, such as [[kumis]], [[Strained yogurt|laban]], [[yogurt]], [[kefir]], and some [[cottage cheese]]s, derive their flavor from lactic acid. The [[casein]] in fermented milk is coagulated (curdled) by lactic acid.
* Lactic acid is also responsible for the sour flavor of [[sourdough]] bread.
* Some beers ([[sour beer]]) purposely contain lactic acid, one such type being Belgian [[lambic]]s. Most commonly, this is produced naturally by various strains of bacteria. These bacteria ferment sugars into acids, unlike the yeast that ferment sugar into ethanol. After cooling the [[wort]], yeast and bacteria are allowed to "fall" into the open fermenters. Brewers of more common beer styles would ensure that no such bacteria are allowed to enter the fermenter. Other sour styles of beer include [[Berliner weisse]], [[Flanders red]] and [[American wild ale]].<ref>{{cite web|url=https://www.morebeer.com/articles/brewing_with_lactic_acid_bacteria|title=Brewing With Lactic Acid Bacteria|website=MoreBeer}}</ref><ref>Lambic (Classic Beer Style) – Jean Guinard</ref>
* In winemaking, a bacterial process, natural or controlled, is often used to convert the naturally present [[malic acid]] to lactic acid, to reduce the sharpness and for other flavor-related reasons. This [[malolactic fermentation]] is undertaken by [[lactic acid bacteria]].
* [[Pickling]] vegetables in brine creates a sour flavor as bacteria convert sugars into lactic acid.
* [[Fermented sausage]]s

In lists of [[nutritional information]] lactic acid might be included under the term "carbohydrate" (or "carbohydrate by difference") because this often includes everything other than water, protein, fat, ash, and ethanol.<ref>{{cite web|title=USDA National Nutrient Database for Standard Reference, Release 28 (2015) Documentation and User Guide|url=http://www.ars.usda.gov/sp2UserFiles/Place/80400525/Data/SR/SR28/sr28_doc.pdf|page=13|date=2015}}</ref> If this is the case then the calculated [[food energy]] may use the standard {{convert|4|kcal}} per gram that is often used for all carbohydrates. But in some cases lactic acid is ignored in the calculation.<ref>For example, in [https://web.archive.org/web/20181116194139/https://ndb.nal.usda.gov/ndb/foods/show/105?n1=%7BQv%3D1%7D this USDA database entry for yoghurt] the food energy is calculated using given coefficients for carbohydrate, fat, and protein. (One must click on "Full report" to see the coefficients.) The calculated value is based on 4.66 grams of carbohydrate, which is exactly equal to the sugars.</ref> The actual energy density of lactic acid is {{convert|3.62|kcal}} per g.<ref name = "FAOSouthgate">{{cite book |last1=Greenfield |first1=Heather |last2=Southgate |first2=D.A.T.  | name-list-style = vanc |date=2003 |title=Food Composition Data: Production, Management and Use |location=Rome |publisher=[[FAO]] |page=146 |isbn=9789251049495 }}</ref>

While not normally found in significant quantities in fruit, lactic acid is the primary organic acid in [[akebia]] fruit, making up 2.12% of the juice.<ref>{{cite journal |author=Li |first1=Li |last2=Yao |first2=Xiaohong |last3=Zhong |first3=Caihong |last4=Chen |first4=Xuzhong |date=January 2010 |title=Akebia: A Potential New Fruit Crop in China |journal=HortScience |volume=45 |pages=4–10 |doi=10.21273/HORTSCI.45.1.4 |doi-access=free |number=1}}</ref>

==== Separately added ====
As a [[food additive]] it is approved for use in the EU,<ref>{{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |publisher=UK Food Standards Agency |title=Current EU approved additives and their E Numbers |access-date=27 October 2011}}</ref> United States<ref>{{cite web |url=https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT|archive-url=https://web.archive.org/web/20100108135705/http://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT|url-status=dead|archive-date=8 January 2010|publisher=US Food and Drug Administration |title=Listing of Food Additives Status Part II |access-date=27 October 2011}}</ref> and Australia and New Zealand;<ref>{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Standard 1.2.4 – Labelling of ingredients |date=8 September 2011 |access-date=27 October 2011|publisher=Australia New Zealand Food Standards Code}}</ref> it is listed by its [[INS number]] 270 or as [[E number]] E270. Lactic acid is used as a food preservative, curing agent, and flavoring agent.<ref name="fda-lactic-acid">{{cite web|title=Listing of Specific Substances Affirmed as GRAS:Lactic Acid|url=http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1061|archive-url=https://web.archive.org/web/20030508142332/http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=184.1061|url-status=dead|archive-date=8 May 2003|publisher=US FDA|access-date=20 May 2013}}</ref> It is an ingredient in processed foods and is used as a decontaminant during meat processing.<ref>{{cite web|title=Purac Carcass Applications|url=http://www.purac.com/EN/Food/Markets/Meat_poultry_and_fish/Applications/Carcass.aspx|publisher=Purac|access-date=20 May 2013|archive-date=29 July 2013|archive-url=https://web.archive.org/web/20130729071937/http://www.purac.com/EN/Food/Markets/Meat_poultry_and_fish/Applications/Carcass.aspx|url-status=dead}}</ref> Lactic acid is produced commercially by fermentation of carbohydrates such as glucose, sucrose, or lactose, or by chemical synthesis.<ref name="fda-lactic-acid" /> Carbohydrate sources include corn, beets, and cane sugar.<ref>{{cite web|title=Agency Response Letter GRAS Notice No. GRN 000240|url=https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153929.htm|archive-url=https://web.archive.org/web/20130825164003/http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153929.htm|url-status=dead|archive-date=25 August 2013|work=FDA|publisher=US FDA|access-date=20 May 2013}}</ref>

=== Forgery ===
Lactic acid has historically been used to assist with the erasure of inks from official papers to be modified during [[forgery]].<ref>{{cite news|url=https://www.nytimes.com/2016/10/02/opinion/sunday/if-i-sleep-for-an-hour-30-people-will-die.html|title=If I Sleep for an Hour, 30 People Will Die | first = Pamela | last = Druckerman | name-list-style = vanc |work=The New York Times|date=2 October 2016}}</ref>

=== Cleaning products ===
Lactic acid is used in some liquid cleaners as a [[descaling agent]]  for removing [[hard water]] deposits such as [[calcium carbonate]].<ref>{{cite book | title = Sustainable Agriculture Reviews 34: Date Palm for Food Medicine and the Environment | url = https://books.google.com/books?id=gBCTDwAAQBAJ | last1 = Naushad | first1 = Mu. | last2 = Lichtfouse | first2 = Eric | date = 2019 | publisher = Springer | page = 162| isbn=978-3-030-11345-2 }}</ref> 

== See also ==
* [[:Category:Lactates|Category: Salts of lactic acid]]
* [[:Category:Lactate esters]]
* [[Acids in wine]]
* [[Alanine cycle]]
* [[Biodegradable plastic]]
* [[Dental caries]]
* [[MCT1]], a lactate transporter
* [[Thiolactic acid]]
* [[Methacrylic acid]]

== References ==
{{Reflist|30em}}

== External links ==
* [http://www.smithsonianmag.com/science-nature/10022381.html Corn Plastic to the Rescue] {{Webarchive|url=https://web.archive.org/web/20131121122758/http://www.smithsonianmag.com/science-nature/10022381.html |date=21 November 2013 }}
* [http://www.webmd.com/a-to-z-guides/lactic-acid Lactic Acid: Information and Resources]
* [https://www.nytimes.com/2006/05/16/health/nutrition/16run.html Lactic Acid Is Not Muscles' Foe, It's Fuel]
* {{cite web |first=Matt |last=Fitzgerald  | name-list-style = vanc |date=January 26, 2010 |title=The Lactic Acid Myths |work=Competitor Running |url=http://running.competitor.com/2010/01/training/the-lactic-acid-myths_7938|archive-url=https://web.archive.org/web/20180825120642/http://running.competitor.com/2010/01/training/the-lactic-acid-myths_7938|archive-date=25 August 2018 |url-status=dead}}

{{Gynecological anti-infectives and antiseptics}}
{{Lactates}}

{{Authority control}}

[[Category:Food acidity regulators]]
[[Category:Alpha hydroxy acids]]
[[Category:Exercise physiology]]
[[Category:Preservatives]]
[[Category:Propionic acids]]
[[Category:E-number additives]]