Butyric acid

Butyric acid (from Ancient Greek: βούτῡρον, meaning "butter"), also known under the systematic name butanoic acid is a carboxylic acid with the structural formula CH3CH2CH2CO2H. Classified as a carboxylic acid, it is an oily, colorless liquid that is soluble in water, ethanol, and ether. Isobutyric acid (2-methylpropanoic acid) is an isomer. Salts and esters of butyric acid are known as butyrates or butanoates. The acid does not occur widely in nature, but its esters are widespread. It is a common industrial chemical.[7]

Butyric acid
Skeletal structure of butyric acid
Flat structure of butyric acid
Space filling model of butyric acid
Preferred IUPAC name
Butanoic acid[1]
Other names
Butyric acid[1]
1-Propanecarboxylic acid
Propanecarboxylic acid
C4:0 (Lipid numbers)
3D model (JSmol)
ECHA InfoCard 100.003.212
EC Number
  • 203-532-3
MeSH Butyric+acid
RTECS number
  • ES5425000
UN number 2820
Molar mass 88.106 g·mol−1
Appearance Colorless liquid
Odor Unpleasant, similar to vomit or body odor
Density 1.135 g/cm3 (−43 °C)[2]
0.9528 g/cm3 (25 °C)[3]
Melting point −5.1 °C (22.8 °F; 268.0 K)[3]
Boiling point 163.75 °C (326.75 °F; 436.90 K)[3]
Sublimes at −35 °C
ΔsublHo = 76 kJ/mol[4]
Solubility Slightly soluble in CCl4Miscible with ethanol, ether
log P 0.79
Vapor pressure 0.112 kPa (20 °C)
0.74 kPa (50 °C)
9.62 kPa (100 °C)[4]
5.35·10−4 L·atm/mol
Acidity (pKa) 4.82
-55.10·10−6 cm3/mol
Thermal conductivity 1.46·105 W/m·K
1.398 (20 °C)[3]
Viscosity 1.814 cP (15 °C)[5]
1.426 cP (25 °C)
Monoclinic (−43 °C)[2]
a = 8.01 Å, b = 6.82 Å, c = 10.14 Å[2]
α = 90°, β = 111.45°, γ = 90°
0.93 D (20 °C)[5]
178.6 J/mol·K[4]
222.2 J/mol·K[5]
−533.9 kJ/mol[4]
2183.5 kJ/mol[4]
Safety data sheet External MSDS
GHS pictograms GHS05: Corrosive[6]
GHS Signal word Danger
P280, P305+351+338, P310[6]
NFPA 704 (fire diamond)
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 fuelHealth code 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no codeNFPA 704 four-colored diamond
Flash point 71 to 72 °C (160 to 162 °F; 344 to 345 K)[6]
440 °C (824 °F; 713 K)[6]
Explosive limits 2.2–13.4%
Lethal dose or concentration (LD, LC):
2000 mg/kg (oral, rat)
Related compounds
Other anions
Propionic acid, Pentanoic acid
Related compounds
Methyl butyrate
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☑Y verify (what is ☑Y☒N ?)
Infobox references


Triglycerides of butyric acid compose 3–4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis.[citation needed] It is one of the fatty acid subgroup called short-chain fatty acids. Butyric acid is a medium-strong acid that reacts with bases and affects many metals.[8] Butyric acid is found in animal fat and plant oils, bovine milk, breast milk,[9] butter, parmesan cheese, and as a product of anaerobic fermentation (including in the colon and as body odor, and vomit).[10] Butyric acid has a taste somewhat like butter and an unpleasant odor. Mammals with good scent detection abilities, such as dogs, can detect it at 10 parts per billion, whereas humans can detect it only in concentrations above 10 parts per million. In food manufacturing, it is used as a flavoring agent.

In humans, butyric acid is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2 (HCA2), a Gi/o-coupled G protein-coupled receptor.[11][12]

Butyric acid or fermentation butyric acid is also present as the ester octyl butyrate in parsnip (Pastinaca sativa)[13] and in the seed of the ginkgo tree.[14]

Preparation and isolationEdit

Butyric acid is prepared industrially by oxidation of butyraldehyde.[7]

It can be separated from aqueous solutions by saturation with salts such as calcium chloride. The calcium salt, Ca(C4H7O2)2·H2O, is less soluble in hot water than in cold.


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. However, 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. 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 substance responsible for the smell of butter.[15] By 1817, he published some of his findings regarding the properties of butyric acid and named it.[16] However, it was not until 1823 that he presented the properties of butyric acid in detail.[17] The name of butyric acid comes from the Latin word for butter, butyrum (or buturum), the substance in which butyric acid was first found.


Butyric acid is used in the preparation of various butyrate esters. It is used to produce cellulose acetate butyrate (CAB), which is used in a wide variety of tools, parts, and coatings, and is more resistant to degradation than cellulose acetate.[18] However, CAB can degrade with exposure to heat and moisture, releasing butyric acid.[19]

Low-molecular-weight esters of butyric acid, such as methyl butyrate, have mostly pleasant aromas or tastes.[7] As a consequence, they are used as food and perfume additives. 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.[20] 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.[21] The substance has also been used as a stink bomb by Sea Shepherd Conservation Society to disrupt Japanese whaling crews.[22]


One pathway for butyrate biosynthesis. Relevant enzymes: acetoacetyl-CoA thiolase, NAD- and NADP-dependent 3-hydroxybutyryl-CoA dehydrogenase, 3-hydroxybutyryl-CoA dehydratase, and NAD-dependent butyryl-CoA dehydrogenase.

Microbial biosynthesisEdit

Butyrate is produced by several fermentation processes performed by obligate anaerobic bacteria.[23] 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 oxidized into acetyl coenzyme A catalyzed by pyruvate:ferredoxin oxidoreductase. Two molecules of carbon dioxide (CO2) and two molecules of elemental hydrogen (H2) are formed as waste products. Subsequently, 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

Other pathways to butyrate include succinate reduction and crotonate disproportionation.

Action Responsible 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

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:

  • acetoacetyl CoA → acetoacetate → acetone
  • acetoacetyl CoA → butyryl CoA → butyraldehyde → butanol

Fermentable fiber sourcesEdit

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.[10][24] One study found that resistant starch consistently produces more butyrate than other types of dietary fiber.[25] The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.[9][26]

Fructans are another source of prebiotic soluble dietary fibers which can be digested to produce butyrate. They are often found in the soluble fibers of foods which are high in sulfur, such as the allium and cruciferous vegetables. Sources of fructans include wheat (although some wheat strains such as spelt contain lower amounts),[27] rye, barley, onion, garlic, Jerusalem and globe artichoke, asparagus, beetroot, chicory, dandelion leaves, leek, radicchio, the white part of spring onion, broccoli, brussels sprouts, cabbage, fennel and prebiotics, such as fructooligosaccharides (FOS), oligofructose, and inulin.[28][29]


Human enzyme and GPCR binding[30][31]
Inhibited enzyme IC50 (nM) Entry note
HDAC1 16,000
HDAC2 12,000
HDAC3 9,000
HDAC4 2,000,000 Lower bound
HDAC5 2,000,000 Lower bound
HDAC6 2,000,000 Lower bound
HDAC7 2,000,000 Lower bound
HDAC8 15,000
HDAC9 2,000,000 Lower bound
CA1 511,000
CA2 1,032,000
GPCR target pEC50 Entry note
FFAR2 2.9–4.6 Full agonist
FFAR3 3.8–4.9 Full agonist
HCA2 2.8 Agonist


Butyric acid is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2 (HCA2, aka GPR109A), a Gi/o-coupled G protein-coupled receptor (GPCR),[11][12]

Like other short-chain fatty acids (SCFAs), butyrate is an agonist at the free fatty acid receptors FFAR2 and FFAR3, which function as nutrient sensors that facilitate the homeostatic control of energy balance;[32][33][34] however, among the group of SCFAs, only butyrate is an agonist of HCA2.[32][33][34] Butyric acid is metabolized by mitochondria, particularly in colonocytes and by the liver, to generate adenosine triphosphate (ATP) during fatty acid metabolism.[32] Butyric acid is also an HDAC inhibitor (specifically, HDAC1, HDAC2, HDAC3, and HDAC8),[30][31] a drug that inhibits the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in cells.[32] Histone acetylation loosens the structure of chromatin by reducing the electrostatic attraction between histones and DNA.[32] In general, it is thought that transcription factors will be unable to access regions where histones are tightly associated with DNA (i.e., non-acetylated, e.g., heterochromatin).[medical citation needed] Therefore, butyric acid is thought to enhance the transcriptional activity at promoters,[32] which are typically silenced or downregulated due to histone deacetylase activity.


Butyrate that is produced in the colon through microbial fermentation of dietary fiber is primarily absorbed and metabolized by colonocytes and the liver[note 1] for the generation of ATP during energy metabolism;[32] however, some butyrate is absorbed in the distal colon, which is not connected to the portal vein, thereby allowing for the systemic distribution of butyrate to multiple organ systems through the circulatory system.[32] Butyrate that has reached systemic circulation can readily cross the blood-brain barrier via monocarboxylate transporters (i.e., certain members of the SLC16A group of transporters).[35][36] Other transporters that mediate the passage of butyrate across lipid membranes include SLC5A8 (SMCT1), SLC27A1 (FATP1), and SLC27A4 (FATP4).[30][36]

Metabolism Edit

Butyric acid is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase.[38] The metabolite produced by this reaction is butyryl–CoA, and is produced as follows:[38]

Adenosine triphosphate + butyric acid + coenzyme A → adenosine monophosphate + pyrophosphate + butyryl-CoA

As a short-chain fatty acid, butyrate is metabolized by mitochondria as an energy (i.e., adenosine triphosphate or ATP) source through fatty acid metabolism.

In humans, the butyrate prodrug tributyrin is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:[39]

Tributyrin + H2O → dibutyrin + butyric acid


Peripheral effectsEdit

Butyrate has numerous effects on energy homeostasis and related diseases (diabetes and obesity), inflammation, and immune function (e.g., it has pronounced antimicrobial and anticarcinogenic effects) in humans.[33][40] These effects occur through its metabolism by mitochondria to generate ATP during fatty acid metabolism or through one or more of its histone-modifying enzyme targets (i.e., the class I histone deacetylases) and G-protein coupled receptor targets (i.e., FFAR2, FFAR3, and HCA2).[33]

Immunomodulation and inflammationEdit

Butyrate's effects on the immune system are mediated through the inhibition of class I histone deacetylases and activation of its G-protein coupled receptor targets: HCA2 (GPR109A), FFAR2 (GPR43), and FFAR3 (GPR41).[34][41] Among the short-chain fatty acids, butyrate is the most potent promoter of intestinal regulatory T cells in vitro and the only one among the group that is an HCA2 ligand.[34] It has been shown to be a critical mediator of the colonic inflammatory response. It possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis and colorectal cancer.

Butyrate has established antimicrobial properties in humans that are mediated through the antimicrobial peptide LL-37, which it induces via HDAC inhibition on histone H3.[41][42][43] In vitro, butyrate increases gene expression of FOXP3 (the transcription regulator for Tregs) and promotes colonic regulatory T cells (Tregs) through the inhibition of class I histone deacetylases;[34][41] through these actions, it increases the expression of interleukin 10, an anti-inflammatory cytokine.[41][34] Butyrate also suppresses colonic inflammation by inhibiting the IFN-γSTAT1 signaling pathways, which is mediated partially through histone deacetylase inhibition. 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.[44]

Similar to other HCA2 agonists studied, butyrate also produces marked anti-inflammatory effects in a variety of tissues, including the brain, gastrointestinal tract, skin, and vascular tissue.[45][46][47] Butyrate binding at FFAR3 induces neuropeptide Y release and promotes the functional homeostasis of colonic mucosa and the enteric immune system.[48]

Butyric acid is an important energy (ATP) source for cells lining the mammalian colon (colonocytes). Without butyric acid for energy, colon cells undergo upregulated autophagy (i.e., self-digestion).[49]


Butyrate produces different effects in healthy and cancerous cells; this is known as the "butyrate paradox". In particular, butyrate inhibits colonic tumor cells and stimulates proliferation of healthy colonic epithelial cells.[50] The signaling mechanism is not well understood.[51] The production of volatile fatty acids such as butyrate from fermentable fibers may contribute to the role of dietary fiber in colon cancer.[24] Short-chain fatty acids, which include butyric acid, are produced by beneficial colonic bacteria (probiotics) that feed on, or ferment prebiotics, which are plant products that contain dietary fiber. These short-chain fatty acids benefit the colonocytes by increasing energy production, and may protect against colon cancer by inhibiting cell proliferation.[52]

Conversely, some researchers have sought to eliminate butyrate and consider it a potential cancer driver.[53] Studies in mice indicate it drives transformation of MSH2-deficient colon epithelial cells.[54]


Butyric acid is an HDAC inhibitor that is selective for class I HDACs in humans.[30] HDACs are histone-modifying enzymes that can cause histone deacetylation and repression of gene expression. HDACs are important regulators of synaptic formation, synaptic plasticity, and long-term memory formation. Several HDACs (specifically, class I HDACs) are known to be involved in mediating the development of an addiction.[55][56][57] Butyric acid and other HDAC inhibitors have been used in preclinical research to assess the transcriptional, neural, and behavioral effects of HDAC inhibition in animals addicted to drugs.[57][58][59]

See alsoEdit


  1. ^ Most of the butyrate that is absorbed into blood plasma from the colon enters the circulatory system via the portal vein;[32] most of the butyrate that enters the circulatory system by this route is taken up by the liver.[32]


  This article incorporates text from a publication now in the public domainChisholm, Hugh, ed. (1911). "Butyric Acid". Encyclopædia Britannica (11th ed.). Cambridge University Press.

  1. ^ a b Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 746. doi:10.1039/9781849733069-00648. ISBN 978-0-85404-182-4.
  2. ^ a b c d Strieter FJ, Templeton DH (1962). "Crystal structure of butyric acid" (PDF). Acta Crystallographica. 15 (12): 1240–1244. doi:10.1107/S0365110X6200328X.
  3. ^ a b c d Lide, David R., ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0.
  4. ^ a b c d e Butanoic acid in Linstrom, Peter J.; Mallard, William G. (eds.); NIST Chemistry WebBook, NIST Standard Reference Database Number 69, National Institute of Standards and Technology, Gaithersburg (MD), http://webbook.nist.gov (retrieved 13 June 2014)
  5. ^ a b c "butanoic acid". Chemister.ru. 19 March 2007. Retrieved 9 May 2016.
  6. ^ a b c d e Sigma-Aldrich Co., Butyric acid. Retrieved on 13 June 2014.
  7. ^ a b c Riemenschneider, Wilhelm (2002). "Carboxylic Acids, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a05_235.
  8. ^ ICSC 1334 – BUTYRIC ACID. Inchem.org (23 November 1998). Retrieved on 2014-03-31.
  9. ^ a b McNabney, S. M.; Henagan, T. M. (2017). "Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance". Nutrients. 9 (12): 1348. doi:10.3390/nu9121348. PMC 5748798. PMID 29231905.
  10. ^ a b Morrison, D. J.; Preston, T. (2016). "Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism". Gut Microbes. 7 (3): 189–200. doi:10.1080/19490976.2015.1134082. PMC 4939913. PMID 26963409.
  11. ^ a b Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP (June 2011). "International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)". Pharmacological Reviews. 63 (2): 269–90. doi:10.1124/pr.110.003301. PMID 21454438.
  12. ^ a b Offermanns S, Colletti SL, IJzerman AP, Lovenberg TW, Semple G, Wise A, Waters MG. "Hydroxycarboxylic acid receptors". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 13 July 2018.
  13. ^ Carroll, Mark J.; Berenbaum, May R. (2002). "Behavioral responses of the parsnip webworm to host plant volatiles". Journal of Chemical Ecology. 28 (11): 2191–2201. doi:10.1023/A:1021093114663. PMID 12523562.
  14. ^ Raven, Peter H.; Evert, Ray F.; Eichhorn, Susan E. (2005). Biology of Plants. W. H. Freemanand Company. pp. 429–431. ISBN 978-0-7167-1007-3. Retrieved 11 October 2018.
  15. ^ 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, 94 : 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.
  16. ^ 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, 3 : 79–81. On p. 81, he named butyric acid: "Ce principe, que j'ai appelé depuis acid butérique, … " (This principle [i.e., constituent], which I have since named "butyric acid", … )
  17. ^ 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.
  18. ^ Lokensgard, Erik (2015). Industrial Plastics: Theory and Applications (6th ed.). Cengage Learning.
  19. ^ Williams, R. Scott. "Care of Plastics: Malignant plastics". WAAC Newsletter. 24 (1). Conservation OnLine. Retrieved 29 May 2017.
  20. ^ Freezer Baits Archived 25 January 2010 at the Wayback Machine, nutrabaits.net
  21. ^ Kasumyan A, Døving K (2003). "Taste preferences in fishes". Fish and Fisheries. 4 (4): 289–347. doi:10.1046/j.1467-2979.2003.00121.x.
  22. ^ Japanese Whalers Injured by Acid-Firing Activists Archived 8 June 2010 at the Wayback Machine, newser.com, 10 February 2010
  23. ^ Seedorf, H.; Fricke, W. F.; Veith, B.; Bruggemann, H.; Liesegang, H.; Strittmatter, A.; Miethke, M.; Buckel, W.; Hinderberger, J.; Li, F.; Hagemeier, C.; Thauer, R. K.; Gottschalk, G. (2008). "The Genome of Clostridium kluyveri, a Strict Anaerobe with Unique Metabolic Features". Proceedings of the National Academy of Sciences. 105 (6): 2128–2133. Bibcode:2008PNAS..105.2128S. doi:10.1073/pnas.0711093105. PMC 2542871. PMID 18218779.
  24. ^ a b Lupton JR (February 2004). "Microbial degradation products influence colon cancer risk: the butyrate controversy". The Journal of Nutrition. 134 (2): 479–82. doi:10.1093/jn/134.2.479. PMID 14747692.
  25. ^ Cummings JH, Macfarlane GT, Englyst HN (February 2001). "Prebiotic digestion and fermentation". The American Journal of Clinical Nutrition. 73 (2 Suppl): 415S–420S. doi:10.1093/ajcn/73.2.415s. PMID 11157351.
  26. ^ Grummer RR (September 1991). "Effect of feed on the composition of milk fat". Journal of Dairy Science. 74 (9): 3244–57. doi:10.3168/jds.S0022-0302(91)78510-X. PMID 1779073.
  27. ^ "Frequently asked questions in the area of diet and IBS". Department of Gastroenterology Translational Nutrition Science, Monash University, Victoria, Australia. Retrieved 24 March 2016.
  28. ^ Gibson, Peter R.; Shepherd, Susan J. (1 February 2010). "Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach". Journal of Gastroenterology and Hepatology. 25 (2): 252–258. doi:10.1111/j.1440-1746.2009.06149.x. ISSN 1440-1746. PMID 20136989.
  29. ^ Gibson, Peter R.; Varney, Jane; Malakar, Sreepurna; Muir, Jane G. (1 May 2015). "Food components and irritable bowel syndrome". Gastroenterology. 148 (6): 1158–1174.e4. doi:10.1053/j.gastro.2015.02.005. ISSN 1528-0012. PMID 25680668.
  30. ^ a b c d "Butyric acid". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 13 July 2018.
  31. ^ a b "butanoic acid, 4 and Sodium; butyrate". BindingDB. The Binding Database. Retrieved 23 May 2015.
  32. ^ a b c d e f g h i j Bourassa MW, Alim I, Bultman SJ, Ratan RR (June 2016). "Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?". Neurosci. Lett. 625: 56–63. doi:10.1016/j.neulet.2016.02.009. PMC 4903954. PMID 26868600.
  33. ^ a b c d Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I (2015). "Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation". Nutrients. 7 (4): 2839–49. doi:10.3390/nu7042839. PMC 4425176. PMID 25875123. Short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A) and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC). Recent evidence suggests that dietary fiber and the gut microbial-derived SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal environment, but also by directly affecting various host peripheral tissues.
  34. ^ a b c d e f Hoeppli RE, Wu D, Cook L, Levings MK (February 2015). "The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome". Front Immunol. 6: 61. doi:10.3389/fimmu.2015.00061. PMC 4332351. PMID 25741338.
    Figure 1: Microbial-derived molecules promote colonic Treg differentiation.
  35. ^ Tsuji A (2005). "Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems". NeuroRx. 2 (1): 54–62. doi:10.1602/neurorx.2.1.54. PMC 539320. PMID 15717057. Other in vivo studies in our laboratories indicated that several compounds including acetate, propionate, butyrate, benzoic acid, salicylic acid, nicotinic acid, and some β-lactam antibiotics may be transported by the MCT at the BBB.21 ... Uptake of valproic acid was reduced in the presence of medium-chain fatty acids such as hexanoate, octanoate, and decanoate, but not propionate or butyrate, indicating that valproic acid is taken up into the brain via a transport system for medium-chain fatty acids, not short-chain fatty acids.
  36. ^ a b Vijay N, Morris ME (2014). "Role of monocarboxylate transporters in drug delivery to the brain". Curr. Pharm. Des. 20 (10): 1487–98. doi:10.2174/13816128113199990462. PMC 4084603. PMID 23789956. Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. ... MCT1 and MCT4 have also been associated with the transport of short chain fatty acids such as acetate and formate which are then metabolized in the astrocytes [78]. ... SLC5A8 is expressed in normal colon tissue, and it functions as a tumor suppressor in human colon with silencing of this gene occurring in colon carcinoma. This transporter is involved in the concentrative uptake of butyrate and pyruvate produced as a product of fermentation by colonic bacteria.
  37. ^ "Butanoate metabolism - Reference pathway". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. 1 November 2017. Retrieved 1 February 2018.
  38. ^ a b "Butyric acid". Human Metabolome Database. University of Alberta. Retrieved 15 August 2015.
  39. ^ "triacylglycerol lipase – Homo sapiens". BRENDA. Technische Universität Braunschweig. Retrieved 25 May 2015.
  40. ^ Tilg H, Moschen AR (September 2014). "Microbiota and diabetes: an evolving relationship". Gut. 63 (9): 1513–1521. doi:10.1136/gutjnl-2014-306928. PMID 24833634.
  41. ^ a b c d Wang G (2014). "Human antimicrobial peptides and proteins". Pharmaceuticals (Basel). 7 (5): 545–94. doi:10.3390/ph7050545. PMC 4035769. PMID 24828484.
    Table 3: Select human antimicrobial peptides and their proposed targets
    Table 4: Some known factors that induce antimicrobial peptide expression
  42. ^ Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S (2012). "Destructive effects of butyrate on the cell envelope of Helicobacter pylori". J. Med. Microbiol. 61 (Pt 4): 582–9. doi:10.1099/jmm.0.039040-0. PMID 22194341.
  43. ^ McGee DJ, George AE, Trainor EA, Horton KE, Hildebrandt E, Testerman TL (2011). "Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37". Antimicrob. Agents Chemother. 55 (6): 2897–904. doi:10.1128/AAC.00016-11. PMC 3101455. PMID 21464244.
  44. ^ Zimmerman MA, Singh N, Martin PM, Thangaraju M, Ganapathy V, Waller JL, Shi H, Robertson KD, Munn DH, Liu K (2012). "Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells". Am. J. Physiol. Gastrointest. Liver Physiol. 302 (12): G1405–15. doi:10.1152/ajpgi.00543.2011. PMC 3378095. PMID 22517765.
  45. ^ Offermanns S, Schwaninger M (2015). "Nutritional or pharmacological activation of HCA(2) ameliorates neuroinflammation". Trends Mol Med. 21 (4): 245–255. doi:10.1016/j.molmed.2015.02.002. PMID 25766751.
  46. ^ Chai JT, Digby JE, Choudhury RP (May 2013). "GPR109A and vascular inflammation". Curr Atheroscler Rep. 15 (5): 325. doi:10.1007/s11883-013-0325-9. PMC 3631117. PMID 23526298.
  47. ^ Graff EC, Fang H, Wanders D, Judd RL (February 2016). "Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2". Metab. Clin. Exp. 65 (2): 102–113. doi:10.1016/j.metabol.2015.10.001. PMID 26773933.
  48. ^ Farzi A, Reichmann F, Holzer P (2015). "The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour". Acta Physiol (Oxf). 213 (3): 603–27. doi:10.1111/apha.12445. PMC 4353849. PMID 25545642.
  49. ^ Donohoe, Dallas R.; Garge, Nikhil; Zhang, Xinxin; Sun, Wei; O’Connell, Thomas M.; Bunger, Maureen K.; Bultman, Scott J. (4 May 2011). "The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon". Cell Metabolism. 13 (5): 517–526. doi:10.1016/j.cmet.2011.02.018. ISSN 1550-4131. PMC 3099420. PMID 21531334.
  50. ^ Vanhoutvin SA, Troost FJ, Hamer HM, Lindsey PJ, Koek GH, Jonkers DM, Kodde A, Venema K, Brummer RJ (2009). Bereswill S (ed.). "Butyrate-induced transcriptional changes in human colonic mucosa". PLOS ONE. 4 (8): e6759. doi:10.1371/journal.pone.0006759. PMC 2727000. PMID 19707587.[permanent dead link]
  51. ^ Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L (August 2004). "Oncogenic Ras promotes butyrate-induced apoptosis through inhibition of gelsolin expression". The Journal of Biological Chemistry. 279 (35): 36680–8. doi:10.1074/jbc.M405197200. PMID 15213223.
  52. ^ Lupton, Joanne R. (2004). Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy. The Journal of Nutrition. 134. vol. 134 no. 2: J. Nutr. pp. 479–482. doi:10.1093/jn/134.2.479. PMID 14747692.CS1 maint: location (link)
  53. ^ "Low-carb diet cuts risk of colon cancer, study finds | University of Toronto Media Room". media.utoronto.ca. Retrieved 4 May 2016.
  54. ^ Belcheva, Antoaneta; Irrazabal, Thergiory; Robertson, Susan J.; Streutker, Catherine; Maughan, Heather; Rubino, Stephen; Moriyama, Eduardo H.; Copeland, Julia K.; Kumar, Sachin (17 July 2014). "Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells". Cell. 158 (2): 288–299. doi:10.1016/j.cell.2014.04.051. ISSN 1097-4172. PMID 25036629.
  55. ^ Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194.
  56. ^ Nestler EJ (January 2014). "Epigenetic mechanisms of drug addiction". Neuropharmacology. 76 Pt B: 259–268. doi:10.1016/j.neuropharm.2013.04.004. PMC 3766384. PMID 23643695.
  57. ^ a b Walker DM, Cates HM, Heller EA, Nestler EJ (February 2015). "Regulation of chromatin states by drugs of abuse". Curr. Opin. Neurobiol. 30: 112–121. doi:10.1016/j.conb.2014.11.002. PMC 4293340. PMID 25486626.
  58. ^ Ajonijebu DC, Abboussi O, Russell VA, Mabandla MV, Daniels WM (August 2017). "Epigenetics: a link between addiction and social environment". Cellular and Molecular Life Sciences. 74 (15): 2735–2747. doi:10.1007/s00018-017-2493-1. PMID 28255755.
  59. ^ Legastelois R, Jeanblanc J, Vilpoux C, Bourguet E, Naassila M (2017). "[Epigenetic mechanisms and alcohol use disorders: a potential therapeutic target]". Biologie Aujourd'hui (in French). 211 (1): 83–91. doi:10.1051/jbio/2017014. PMID 28682229.

External linksEdit