Lactic acid is anorganic acid with the molecular formulaC3H6O3. In its solid state, it is white andmiscible with water.[5] When dissolved, it forms a colorless solution. Production includes both artificial synthesis and natural sources. Lactic acid is analpha-hydroxy acid (AHA) due to the presence of ahydroxyl group adjacent to thecarboxyl group. It is a synthetic intermediate in manyorganic synthesis industries and in variousbiochemical industries. Theconjugate base of lactic acid is calledlactate (or the lactate anion). The name of the derivedacyl group islactoyl.
In solution, it can ionize by a loss of a proton to produce the lactateionCH 3CH(OH)CO− 2, also known as 2-hydroxypropanoate. Compared toacetic acid, itspKa is 1 unit less, meaning that lactic acid is ten times more acidic than acetic acid. This higher acidity is the consequence of intramolecular hydrogen bonding between the α-hydroxyl and the carboxylate group.
Lactic acid ischiral, consisting of twoenantiomers. One is known asL-lactic acid, (S)-lactic acid, or (+)-lactic acid, and the other, its mirror image, isD-lactic acid, (R)-lactic acid, or (−)-lactic acid. A mixture of the two in equal amounts is calledDL-lactic acid, orracemic lactic acid. Lactic acid ishygroscopic.DL-Lactic acid ismiscible with water and with ethanol above its melting point, which is 16–18 °C (61–64 °F).D-Lactic acid andL-lactic acid have a higher melting point. Lactic acid produced by fermentation of milk is often racemic, although certain species of bacteria produce solelyD-lactic acid.[6] On the other hand, lactic acid produced by fermentation in animal muscles has the (L) enantiomer and is sometimes called "sarcolactic" acid, from the Greeksarx, meaning "flesh".
In animals,L-lactate is constantly produced frompyruvate via theenzymelactate dehydrogenase (LDH) in a process offermentation during normalmetabolism andexercise.[7] 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, includingmonocarboxylate transporters, concentration and isoform of LDH, and oxidative capacity of tissues.[7] This reaction is reversible and redox-linked: LDH reduces pyruvate to lactate using NADH as an electron donor, simultaneously regeneratingNAD⁺ required for glycolysis under anaerobic conditions.[8] The concentration ofblood lactate is usually1–2mMTooltip millimolar at rest, but can rise to over 20mM during intense exertion and as high as 25mM afterward.[9][10] In addition to other biological roles,L-lactic acid is the primaryendogenousagonist ofhydroxycarboxylic acid receptor 1 (HCA1), which is aGi/o-coupledG protein-coupled receptor (GPCR).[11][12]
Lactic acid is produced in human tissues when the demand for oxygen is limited by the supply. This occurs during tissueischemia 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 oflactic acidosis produces lactic acid, which results in anoxygen debt, which can be resolved or repaid when tissue oxygenation improves.[17]
Swedish chemistCarl Wilhelm Scheele was the first person to isolate lactic acid in 1780 from sourmilk.[18] The name reflects thelact- combining form derived from the Latin wordlac, meaning "milk". In 1808,Jöns Jacob Berzelius discovered that lactic acid (actuallyL-lactate) is also produced inmuscles during exertion.[19] Its structure was established byJohannes Wislicenus in 1873.
Due to a combination of geographic and infrastructural factors, theSoviet Union, as well as several other members of theWarsaw Pact, experienced chronic shortages ofcitric andmalic acid, among others.[citation needed] In order to combat this issue, theNarkomzem (Soviet Ministry of Agriculture) invested heavily in the development of suitable lactobacillus strains, which were able to produce lactic acid with relatively high efficiency from crude molasses feedstock.[20] Despite synthetic citric acid being produced in some quantities across the Warsaw Pact, it proved far more difficult to purify, leading to lactic acid being, on average, a quarter of the cost of citric acid. The continued use of lactic acid in someEastern European andCentral Asian food production in the modern day, in favor of the more common citric or malic acids, lends it a distinctive flavor.[citation needed]
Global demand for lactic acid continues to expand, with an estimated annual growth rate of 5–8% driven by the increasing use of biodegradable plastics, green solvents, and pharmaceutical intermediates. Worldwide production exceeded 1.5 million tonnes by the early 2020s, up from roughly 275,000 tonnes in 2006, and is projected to keep rising as biobased materials replace petroleum-derived products.[21] Major producers includeNatureWorks LLC, Purac, Galactic, and several Chinese manufacturers. NatureWorks operates one of the world’s largestpolylactic acid (PLA) facilities inBlair, Nebraska, with a production capacity of about 140,000 tonnes per year, supplying feedstock for a wide range ofbiodegradable packaging and fiber applications.[22]
Lactic acid is produced industrially by bacterialfermentation ofcarbohydrates, or by chemical synthesis fromacetaldehyde.[23] As of 2009[update], lactic acid was produced predominantly (70–90%)[24] by fermentation. Production of racemic lactic acid consisting of a 1:1 mixture ofD andL stereoisomers, or of mixtures with up to 99.9%L-lactic acid, is possible by microbial fermentation. Industrial production of the D-lactic acid enantiomer is technically more challenging because most naturally occurring lactic acid bacteria preferentially produce the L-form; obtaining high optical purity of D-lactic acid therefore requiresgenetically engineered microorganisms or specific D-lactate dehydrogenases.[22]
As a starting material for industrial production of lactic acid, almost any carbohydrate source containingC 5 (pentose sugar) andC 6 (hexose sugar) can be used. Puresucrose,glucose fromstarch, raw sugar, and beet juice are frequently used.[25] Lactic acid producing bacteria can be divided in two classes: homofermentative bacteria likeLactobacillus casei andLactococcus 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 ascarbon dioxide andacetic acid/ethanol.[26]
Racemic lactic acid is synthesized industrially by reactingacetaldehyde withhydrogen cyanide and hydrolysing the resultantlactonitrile. Whenhydrolysis is performed byhydrochloric 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.[27] Synthesis of both racemic and enantiopure lactic acids is also possible from other starting materials (vinyl acetate,glycerol, etc.) by application of catalytic procedures.[28]
During power exercises such assprinting, when the rate of demand for energy is high,glucose is broken down and oxidized topyruvate, 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 forNAD+ regeneration (pyruvate is reduced to lactate while NADH is oxidized to NAD+), which is used up in oxidation ofglyceraldehyde 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+ quickly enough, so pyruvate is converted to lactate to allow energy production byglycolysis to continue.[29]
If blood glucose concentrations are high, the glucose can be used to build up the liver'sglycogen 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.[29] Some sources of excess lactate production are metabolism inred blood cells, which lackmitochondria that perform aerobic respiration, and limitations in the rates of enzyme activity in muscle fibers during intense exertion.[30]Lactic acidosis is aphysiological condition characterized by accumulation of lactate (especiallyL-lactate), with formation of an excessively high proton concentration [H+] and correspondingly lowpH in the tissues, a form ofmetabolic acidosis.[29]
The first stage in metabolizing glucose isglycolysis, the conversion of glucose to pyruvate− and H+:
When sufficient oxygen is present for aerobic respiration, the pyruvate is oxidized toCO2 and water by the Krebs cycle, in whichoxidative 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− bylactate dehydrogenase), a process that absorbs these protons:[31]
The production of lactate from glucose (glucose → 2 lactate− + 2 H+), when viewed in isolation, releases two H+. The H+ are absorbed in the production of ATP, but H+ is subsequently released during hydrolysis of ATP:
ATP4− + H2O → ADP3− + HPO2−4 + H+
Once the production and use of ATP is included, the overall reaction is
C6H12O6 → 2 CH3CH(OH)CO−2 + 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 toCO2 and water for the production of ATP.[29]
Lactate production and export contribute significantly to intracellular pH regulation in metabolically active tissues. Inskeletal muscle, accumulation of lactic acid lowers intracellular pH, andmonocarboxylate transporters facilitate the efflux of both lactate and H⁺, thereby helping maintainacid-base homeostasis and delaying fatigue.[32]
Althoughglucose is usually assumed to be the main energy source for living tissues, there is evidence that lactate, in preference to glucose, is preferentially metabolized byneurons in thebrains of severalmammalian species that includemice,rats, andhumans.[33][34][29] According to thelactate-shuttle hypothesis,glial cells are responsible for transforming glucose into lactate, and for providing lactate to the neurons.[35][36] Because of this local metabolic activity of glial cells, theextracellular fluid immediately surrounding neurons strongly differs in composition from theblood orcerebrospinal fluid, being much richer with lactate, as was found inmicrodialysis studies.[33]
Some evidence suggests that lactate is important at early stages of development for brain metabolism inprenatal and earlypostnatal subjects, with lactate at these stages having higher concentrations in body liquids, and being utilized by the brain preferentially over glucose.[33] It was also hypothesized that lactate may exert a strong action overGABAergic networks in thedeveloping brain, making them moreinhibitory than it was previously assumed,[37] acting either through better support of metabolites,[33] or alterations in base intracellularpH levels,[38][39] or both.[40]
Studies of brain slices of mice show thatβ-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 metabolismin vitro.[41] 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."[42]
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.[18]
Reference ranges for blood tests, comparing lactate content (shown in violet at center-right) to other constituents in human blood
Blood tests for lactate are performed to determine the status of theacid base homeostasis in the body.Blood sampling for this purpose is oftenarterial (even if it is more difficult thanvenipuncture), because lactate levels differ substantially between arterial and venous, and the arterial level is more representative for this purpose.
Lactic acid is also employed inpharmaceutical technology to produce water-soluble lactates from otherwise-insoluble active ingredients. It finds further use in topical preparations andcosmetics to adjust acidity and for itsdisinfectant andkeratolytic properties.
Lactic acid containing bacteria have shown promise in reducingoxaluria with its descaling properties on calcium compounds.[47]
Lactic acid is also responsible for the sour flavor ofsourdough bread.
Some beers (sour beer) purposely contain lactic acid, one such type being Belgianlambics. 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 thewort, 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 includeBerliner weisse,Flanders red andAmerican wild ale.[48][49]
In winemaking, a bacterial process, natural or controlled, is often used to convert the naturally presentmalic acid to lactic acid, to reduce the sharpness and for other flavor-related reasons. Thismalolactic fermentation is undertaken bylactic acid bacteria.
Pickling vegetables in brine creates a sour flavor as bacteria convert sugars into lactic acid.
In lists ofnutritional 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.[50] If this is the case then the calculatedfood energy may use the standard 4 kcal/g (17 kJ/g) that is often used for all carbohydrates. But in some cases lactic acid is ignored in the calculation.[51] The actual energy density of lactic acid is 3.62 kcal/g (15.1 kJ/g).[52]
While not normally found in significant quantities in fruit, lactic acid is the primary organic acid inakebia fruit, making up 2.12% of the juice.[53]
As afood additive it is approved for use in the EU,[54] United States[55] and Australia and New Zealand;[56] it is listed by itsINS number 270 or asE number E270. Lactic acid is used as a food preservative, curing agent, and flavoring agent.[57] It is an ingredient in processed foods and is used as a decontaminant during meat processing.[58] Lactic acid is produced commercially by fermentation of carbohydrates such as glucose, sucrose, or lactose, or by chemical synthesis.[57] Carbohydrate sources include corn, beets, and cane sugar.[59]
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^For example, inthis 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.
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