Butyric acid

Butyric acid
Names
IUPAC name
Butanoic acid
Other names
Butyric acid, 1-Propanecarboxylic acid, Propanecarboxylic acid, C4:0 (Lipid numbers)
Identifiers
107-92-6 Yes
ChEBI CHEBI:30772 Yes
ChEMBL ChEMBL14227 Yes
ChemSpider 259 Yes
DrugBank DB03568 Yes
EC number 203-532-3
IUPHAR ligand 1059
Jmol-3D images Image
Image
KEGG C00246 Yes
MeSH Butyric+acid
PubChem 264
RTECS number ES5425000
UNII 40UIR9Q29H Yes
UN number 2820
Properties
Molecular formula
 C4H8O2
Molar mass 88.11 g·mol−1
Appearance Colorless liquid
Odor Unpleasant and obnoxious
Density 1.135 g/cm3 (−43 °C)[1]
0.9528 g/cm3 (25 °C)[2]
Melting point −5.1 °C (22.8 °F; 268.0 K)[2]
Boiling point 163.75 °C (326.75 °F; 436.90 K)[2]
Sublimes at −35 °C
ΔsublHo = 76 kJ/mol[3]
Miscible
Solubility Slightly soluble in CCl4[4]
Miscible with ethanol, ether
log P 0.79[4]
Vapor pressure 0.112 kPa (20 °C)[5]
0.74 kPa (50 °C)
9.62 kPa (100 °C)[3]
5.35·10−4 L·atm/mol[4]
Acidity (pKa) 4.82[4]
Thermal conductivity 1.46·105 W/m·K
1.398 (20 °C)[2]
Viscosity 1.814 cP (15 °C)[6]
0.1426 cP (25 °C)[4]
Structure
Crystal structure Monoclinic (−43 °C)[1]
Space group C2/m[1]
Lattice constant a = 8.01 Å, b = 6.82 Å, c = 10.14 Å[1]
Lattice constant α = 90°, β = 111.45°, γ = 90°
Dipole moment 0.93 D (20 °C)[6]
Thermochemistry
Specific
heat capacity (C)
 178.6 J/mol·K[3][4]
222.2 J/mol·K[6]
Std enthalpy of
formation (ΔfHo298)
 −533.9 kJ/mol[3]
Std enthalpy of
combustion (ΔcHo298)
 2183.5 kJ/mol[3]
Hazards
MSDS External MSDS
GHS pictograms [7]
GHS signal word Danger
H314[7]
P280, P305+351+338, P310[7]
EU classification Xn C
R-phrases R20/21/22, R34, R36/37/38
S-phrases S26, S36, S45
NFPA 704
Flammability code 2: Must be moderately heated or exposed to relatively high ambient temperature before ignition can occur. Flash point between 38 and 93 °C (100 and 200 °F). E.g., diesel fuel Health code 3: Short exposure could cause serious temporary or residual injury. E.g., chlorine gas Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
2
3
0
Flash point 71 to 72 °C (160 to 162 °F; 344 to 345 K)[5][7]
440 °C (824 °F; 713 K)[7]
Explosive limits 2.2–13.4%[5]
2000 mg/kg (oral, rat)
Related compounds
Other anions
 Butyrate
Propionic acid
Acrylic acid
Succinic acid
Malic acid
Tartaric acid
Crotonic acid
Fumaric acid
Pentanoic acid
Related compounds
 1-Butanol
Butyraldehyde
Methyl butyrate
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 Yes verify (what is: Yes/?)
Infobox references

Butyric acid (from Greek βούτῡρον, meaning "butter"), also known under the systematic name butanoic acid, abbreviated BTA,[5] is a carboxylic acid with the structural formula CH3CH2CH2-COOH. Salts and esters of butyric acid are known as butyrates or butanoates. Butyric acid is found in milk, especially goat, sheep and buffalo milk, butter, Parmesan cheese, and as a product of anaerobic fermentation (including in the colon and as body odor). It has an unpleasant smell and acrid taste, with a sweetish aftertaste (similar to ether). It can be detected by mammals with good scent detection abilities (such as dogs) at 10 ppb, whereas humans can detect it in concentrations above 10 ppm.

Butyric acid is present in, and is the main distinctive smell of, human vomit.[8][9][10]

Butyric acid was first observed (in impure form) in 1814 by the French chemist Michel Eugène Chevreul. By 1818, he had purified it sufficiently to characterize it.[11] The name of butyric acid comes from the Latin word for butter, butyrum (or buturum), the substance in which butyric acid was first found.

Chemistry

Butyric acid is a fatty acid occurring in the form of esters in animal fats. The triglyceride of butyric acid makes up 3% to 4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis, leading to the unpleasant odor. It is an important member of the fatty acid subgroup called short-chain fatty acids. Butyric acid is a medium-strong acid that reacts with bases and strong oxidants, and attacks many metals.[12]

The acid is an oily, colorless liquid that is easily soluble in water, ethanol, and ether, and can be separated from an aqueous phase by saturation with salts such as calcium chloride. It is oxidized to carbon dioxide and acetic acid using potassium dichromate and sulfuric acid, while alkaline potassium permanganate oxidizes it to carbon dioxide. The calcium salt, Ca(C4H7O2)2·H2O, is less soluble in hot water than in cold.

Butyric acid has a structural isomer called isobutyric acid (2-methylpropanoic acid).

Production

It is industrially prepared by the fermentation of sugar or starch, brought about by the addition of putrefying cheese, with calcium carbonate added to neutralize the acids formed in the process. The butyric fermentation of starch is aided by the direct addition of Bacillus subtilis. Salts and esters of the acid are called butyrates or butanoates.

Butyric acid or fermentation butyric acid is also found as a hexyl ester hexyl butyrate in the oil of Heracleum giganteum (a type of hogweed) and as the octyl ester octyl butyrate in parsnip (Pastinaca sativa); it has also been noticed in skin flora and perspiration.

Uses

Butyric acid is used in the preparation of various butyrate esters. Low-molecular-weight esters of butyric acid, such as methyl butyrate, have mostly pleasant aromas or tastes. As a consequence, they find use as food and perfume additives. It is also used as an animal feed supplement, due to the ability to reduce pathogenic bacterial colonization.[13] It is an approved food flavoring in the EU FLAVIS database (number 08.005).

Due to its powerful odor, it has also been used as a fishing bait additive.[14] Many of the commercially available flavors used in carp (Cyprinus carpio) baits use butyric acid as their ester base; however, it is not clear whether fish are attracted by the butyric acid itself or the substances added to it. Butyric acid was, however, one of the few organic acids shown to be palatable for both tench and bitterling.[15]

The substance has also been used as a stink bomb by Sea Shepherd Conservation Society to disrupt Japanese whaling crews,[16] as well as by anti-abortion protesters to disrupt abortion clinics.[17]

Biochemistry

Biosynthesis

Butyrate is produced as end-product of a fermentation process solely performed by obligate anaerobic bacteria. Fermented Kombucha "tea" includes butyric acid as a result of the fermentation. This fermentation pathway was discovered by Louis Pasteur in 1861. Examples of butyrate-producing species of bacteria:

The pathway starts with the glycolytic cleavage of glucose to two molecules of pyruvate, as happens in most organisms. Pyruvate is then oxidized into acetyl coenzyme A using a unique mechanism that involves an enzyme system called pyruvate-ferredoxin oxidoreductase. Two molecules of carbon dioxide (CO2) and two molecules of elemental hydrogen (H2) are formed as waste products from the cell. Then,

ActionResponsible enzyme
Acetyl coenzyme A converts into acetoacetyl coenzyme A acetyl-CoA-acetyl transferase
Acetoacetyl coenzyme A converts into β-hydroxybutyryl CoA β-hydroxybutyryl-CoA dehydrogenase
β-hydroxybutyryl CoA converts into crotonyl CoA crotonase
Crotonyl CoA converts into butyryl CoA (CH3CH2CH2C=O-CoA) butyryl CoA dehydrogenase
A phosphate group replaces CoA to form butyryl phosphate phosphobutyrylase
The phosphate group joins ADP to form ATP and butyrate butyrate kinase

ATP is produced, as can be seen, in the last step of the fermentation. Three molecules of ATP are produced for each glucose molecule, a relatively high yield. The balanced equation for this fermentation is

C6H12O6 → C4H8O2 + 2 CO2 + 2 H2.

Several species form acetone and n-butanol in an alternative pathway, which starts as butyrate fermentation. Some of these species are:

These bacteria begin with butyrate fermentation, as described above, but, when the pH drops below 5, they switch into butanol and acetone production to prevent further lowering of the pH. Two molecules of butanol are formed for each molecule of acetone.

The change in the pathway occurs after acetoacetyl CoA formation. This intermediate then takes two possible pathways:

Highly-fermentable fiber residues, such as those from resistant starch, oat bran, pectin, and guar are transformed by colonic bacteria into short-chain fatty acids (SCFA) including butyrate, producing more SCFA than less fermentable fibers such as celluloses.[18] One study found that resistant starch consistently produces more butyrate than other types of dietary fiber.[19] The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.[20]

Cancer

The role of butyrate differs between normal and cancerous cells. This is known as the "butyrate paradox". Butyrate inhibits colonic tumor cells, and promotes healthy colonic epithelial cells;[21] but the signaling mechanism is not well understood.[22] A review suggested the chemopreventive benefits of butyrate depend in part on amount, time of exposure with respect to the tumorigenic process, and the type of fat in the diet.[18] The production of volatile fatty acids such as butyrate from fermentable fibers may contribute to the role of dietary fiber in colon cancer.[18]

Butyric acid can act as an HDAC inhibitor, inhibiting the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in the cell. Acetylated histones have a lower affinity for DNA than nonacetylated histones, due to the neutralization of electrostatic charge interactions. In general, it is thought that transcription factors will be unable to access regions where histones are tightly associated with DNA (i.e., nonacetylated, e.g., heterochromatin). Therefore, butyric acid is thought to enhance the transcriptional activity at promoters, which are typically silenced or downregulated due to histone deacetylase activity.

Two HDAC inhibitors, sodium butyrate (NaB) and trichostatin A (TSA), increase lifespan in experimental animals.[23]

Butyrate is a major metabolite in colonic lumen arising from bacterial fermentation of dietary fiber and has been shown to be a critical mediator of the colonic inflammatory response. Butyrate possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis (UC) and colorectal cancer. One mechanism underlying butyrate function in suppression of colonic inflammation is inhibition of the IFN-γ/STAT1 signaling pathways at least partially through acting as a histone deacetylase (HDAC) inhibitor. While transient IFN-γ signaling is generally associated with normal host immune response, chronic IFN-γ signaling is often associated with chronic inflammation. It has been shown that Butyrate inhibits activity of HDAC1 that is bound to the Fas gene promoter in T cells, resulting in hyperacetylation of the Fas promoter and up-regulation of Fas receptor on the T cell surface.[24] It is thus suggested that Butyrate enhances apoptosis of T cells in the colonic tissue and thereby eliminates the source of inflammation (IFN-γ production).[25]

Safety

The United States Environmental Protection Agency rates and regulates butyric acid as a toxic substance.[26]

Personal protective equipment such as rubber or PVC gloves, protective eye goggles, and chemical-resistant clothing and shoes are used to minimize risks when handling butyric acid.

Inhalation of butyric acid may result in soreness of throat, coughing, a burning sensation and laboured breathing. Ingestion of the acid may result in abdominal pain, shock, and collapse. Physical exposure to the acid may result in pain, blistering and skin burns, while exposure to the eyes may result in pain, severe deep burns and loss of vision.[12]

See also

References

Public Domain This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). Encyclopædia Britannica (11th ed.). Cambridge University Press.

  1. ↑ 1.0 1.1 1.2 1.3 Strieter, F. J.; Templeton, D. H. (1962). "Crystal structure of butyric acid". Acta Crystallographica 15 (12): 1240. doi:10.1107/S0365110X6200328X.
  2. ↑ 2.0 2.1 2.2 2.3 Lide, David R., ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Butanoic acid in Linstrom, P.J.; Mallard, W.G. (eds.) NIST Chemistry WebBook, NIST Standard Reference Database Number 69. National Institute of Standards and Technology, Gaithersburg MD. http://webbook.nist.gov (retrieved 2014-06-13)
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 CID 264 from PubChem
  5. ↑ 5.0 5.1 5.2 5.3 "Butanoic Acid". http://www.caslab.com''. ALS Environmental. Retrieved 2014-06-13.
  6. ↑ 6.0 6.1 6.2 http://chemister.ru/Database/properties-en.php?dbid=1&id=1985
  7. ↑ 7.0 7.1 7.2 7.3 7.4 Sigma-Aldrich Co., Butyric acid. Retrieved on 2014-06-13.
  8. ↑ What Is Butyric Acid? (with pictures). Wisegeek.org (2014-03-19). Retrieved on 2014-03-31.
  9. ↑ HMDB: Showing metabocard for Butyric acid (HMDB00039). Hmdb.ca. Retrieved on 2014-03-31.
  10. ↑ Butyric acid. New World Encyclopedia. Retrieved on 2014-03-31.
  11. ↑ Unfortunately, Chevreul did not publish his early research on butyric acid; instead, he deposited his findings in manuscript form with the secretary of the Academy of Sciences in Paris, France. This led to problems because Henri Braconnot, a French chemist, was also researching the composition of butter and was publishing his findings, and this led to disputes about priority. As early as 1815, Chevreul claimed that he had found the susbstance that's responsible for the smell of butter: Chevreul (1815) "Lettre de M. Chevreul à MM. les rédacteurs des Annales de chimie" (Letter from Mr. Chevreul to the editors of the Annals of Chemistry), Annales de chimie, vol. 94, pages 73–79; in a footnote spanning pages 75–76, he mentions that he had found a substance that is responsible for the smell of butter. By 1817, he published some of his findings regarding the properties of butyric acid: Chevreul (1817) "Extrait d'une lettre de M. Chevreul à MM. les Rédacteurs du Journal de Pharmacie" (Extract of a letter from Mr. Chevreul to the editors of the Journal of Pharmacy), Journal de Pharmacie et des sciences accessoires, vol. 3, pages 79–81. However, it was not until 1823 that he presented the properties of butyric acid in detail: E. Chevreul, Recherches chimiques sur les corps gras d'origine animale [Chemical researches on fatty substances of animal origin] (Paris, France: F.G. Levrault, 1823), pages 115–133.
  12. ↑ 12.0 12.1 ICSC 1334 – BUTYRIC ACID. Inchem.org (1998-11-23). Retrieved on 2014-03-31.
  13. ↑ Supplementation of Coated Butyric Acid in the Feed Reduces Colonization and Shedding of Salmonella in Poultry. Ps.fass.org. Retrieved on 2014-03-31.
  14. ↑ Freezer Baits, nutrabaits.net
  15. ↑ Kasumyan, A.O.; Døving, K.B. (2003). "Taste preferences in fishes". Fish and Fisheries 4 (4): 289–347. doi:10.1046/j.1467-2979.2003.00121.x.
  16. ↑ Japanese Whalers Injured by Acid-Firing Activists, newser.com, February 10, 2010
  17. ↑ National Abortion Federation, HISTORY OF VIOLENCE Butyric Acid Attacks. Prochoice.org. Retrieved on 2014-03-31.
  18. ↑ 18.0 18.1 18.2 Lupton, Joanne R. (2004). "Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy". Journal of Nutrition 134 (2): 479–82. PMID 14747692.
  19. ↑ Cummings JH, Macfarlane GT, Englyst HN (2001). "Prebiotic digestion and fermentation". American Journal of Clinical Nutrition 73 (suppl): 415S–20S. PMID 11157351.
  20. ↑ Grummer, Ric R. (1991). "Effect of feed on the composition of milk fat" (PDF). J Dairy Sci 74 (9): 3244–57. doi:10.3168/jds.S0022-0302(91)78510-X. PMID 1779073.
  21. ↑ Vanhoutvin, SA; Troost, FJ; Hamer, HM; Lindsey, PJ; Koek, GH; Jonkers, DM; Kodde, A; Venema, K; Brummer, RJ (2009). Bereswill, Stefan, ed. "Butyrate-Induced Transcriptional Changes in Human Colonic Mucosa". PLoS ONE 4 (8): e6759. doi:10.1371/journal.pone.0006759. PMC 2727000. PMID 19707587.
  22. ↑ Klampfer, L; Huang, J; Sasazuki, T; Shirasawa, S; Augenlicht, L (2004). "Oncogenic Ras Promotes Butyrate-induced Apoptosis through Inhibition of Gelsolin Expression" (PDF). The Journal of Biological Chemistry 279 (35): 36680–8. doi:10.1074/jbc.M405197200. PMID 15213223.
  23. ↑ Zhang, M; Poplawski, M; Yen, K; Cheng, H; Bloss, E; Zhu, X; Patel, H; Mobbs, CV; Dillin, Andy (2009). Dillin, Andy, ed. "Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling". PLoS Biology 7 (11): e1000245. doi:10.1371/journal.pbio.1000245. PMC 2774267. PMID 19924292.
  24. ↑ Zimmerman, M. A.; Singh, N; Martin, P. M.; Thangaraju, M; Ganapathy, V; Waller, J. L.; Shi, H; Robertson, K. D.; Munn, D. H.; Liu, K (2012). "Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells". AJP: Gastrointestinal and Liver Physiology 302 (12): G1405–15. doi:10.1152/ajpgi.00543.2011. PMC 3378095. PMID 22517765.
  25. ↑ Mary A. Zimmerman, Nagendra Singh, Pamela M. Martin, Muthusamy Thangaraju, Vadivel Ganapathy, Jennifer L. Waller, Huidong Shi, Keith D. Robertson, David H. Munn, and Kebin Liu. 2012. Butyrate suppresses colonic inflammation through HDAC1-dependent Fas Upregulation and Fas-mediated apoptosis of T cells. Am J Physiol Gastrointest Liver Physiol 302: G1405-G1415
  26. ↑ Butyric Acid. Scorecard.goodguide.com. Retrieved on 2014-03-31.

External links

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