Butyric acid

Butyric acid Skeletal structure of butyric acid Flat structure of butyric acid Space filling model of butyric acid Names Preferred IUPAC name Butanoic acid[1] Other names Ethylacetic acid 1-Propanecarboxylic acid Propylformic acid C4:0 (Lipid numbers) Identifiers CAS Number Butyric acid: 107-92-6 check Butyrate: 461-55-2 check 3D model (JSmol) Butyric acid: Interactive image ChEBI Butyric acid: CHEBI:30772 check ChEMBL Butyric acid: ChEMBL14227 check ChemSpider Butyric acid: 259 check Butyrate: 94582 check DrugBank Butyric acid: DB03568 check ECHA InfoCard 100.003.212 Edit this at Wikidata EC Number Butyric acid: 203-532-3 IUPHAR/BPS Butyric acid: 1059 KEGG Butyric acid: C00246 check MeSH Butyric+acid PubChem CID Butyric acid: 264 Butyrate: 104775 RTECS number Butyric acid: ES5425000 UNII Butyric acid: 40UIR9Q29H check UN number 2820 CompTox Dashboard (EPA) Butyric acid: DTXSID8021515 Edit this at Wikidata InChI SMILES Properties Chemical formula C 3H 7COOH 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] Sublimation conditions Sublimes at −35 °C ΔsublHo = 76 kJ/mol[4] Solubility in water Miscible Solubility Miscible with ethanol, ether. Slightly soluble in CCl4 log P 0.79 Vapor pressure 0.112 kPa (20 °C) 0.74 kPa (50 °C) 9.62 kPa (100 °C)[4] Henry's law constant (kH) 5.35·10−4 L·atm/mol Acidity (pKa) 4.82 Magnetic susceptibility (χ) -55.10·10−6 cm3/mol Thermal conductivity 1.46·105 W/m·K Refractive index (nD) 1.398 (20 °C)[3] Viscosity 1.814 cP (15 °C)[5] 1.426 cP (25 °C) Structure Crystal structure Monoclinic (−43 °C)[2] Space group C2/m[2] Lattice constant a = 8.01 Å, b = 6.82 Å, c = 10.14 Å[2] α = 90°, β = 111.45°, γ = 90° Dipole moment 0.93 D (20 °C)[5] Thermochemistry Heat capacity (C) 178.6 J/mol·K[4] Std molar entropy (So298) 222.2 J/mol·K[5] Std enthalpy of formation (ΔfH⦵298) −533.9 kJ/mol[4] Std enthalpy of combustion (ΔcH⦵298) 2183.5 kJ/mol[4] Hazards Safety data sheet External MSDS GHS pictograms GHS05: Corrosive[6] GHS Signal word Danger GHS hazard statements H314[6] GHS precautionary statements P280, P305+351+338, P310[6] NFPA 704 (fire diamond) NFPA 704 four-colored diamond 320 Flash point 71 to 72 °C (160 to 162 °F; 344 to 345 K)[6] Autoignition temperature 440 °C (824 °F; 713 K)[6] Explosive limits 2.2–13.4% Lethal dose or concentration (LD, LC): LD50 (median dose) 2000 mg/kg (oral, rat) Related compounds Related Carboxylic acids Propionic acid, Pentanoic acid Related compounds 1-Butanol Butyraldehyde Methyl butyrate Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references Butyric acid (from Ancient Greek: βούτῡρον, meaning "butter"), also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula CH3CH2CH2CO2H. It is an oily, colorless liquid with an unpleasant odor. 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] and an important component in the mammalian gut. Contents 1 History 2 Occurrence 3 Production 3.1 Industrial 3.2 Microbial biosynthesis 3.3 Fermentable fiber sources 4 Reactions 5 Uses 6 Pharmacology 6.1 Pharmacodynamics 6.2 Pharmacokinetics 6.3 Metabolism 7 Biochemistry 7.1 In the mammalian gut 7.1.1 Immunomodulation and inflammation 7.1.2 Cancer 7.1.3 Potential treatments from butyrate restoration 7.2 Addiction 8 Butyrate salts and esters 8.1 Examples 8.1.1 Salts 8.1.2 Esters 9 See also 10 Notes 11 References 12 External links History 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.[8] By 1817, he published some of his findings regarding the properties of butyric acid and named it.[9] However, it was not until 1823 that he presented the properties of butyric acid in detail.[10] The name butyric acid comes from Ancient Greek: βούτῡρον, meaning "butter", the substance in which it was first found. The Latin name butyrum (or buturum) is similar. Occurrence Triglycerides of butyric acid compose 3–4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis.[11] It is one of the fatty acid subgroup called short-chain fatty acids. Butyric acid is a typical carboxylic acid that reacts with bases and affects many metals.[12] It is found in animal fat and plant oils, bovine milk, breast milk, butter, parmesan cheese, body odor, vomit, and as a product of anaerobic fermentation (including in the colon).[13][14] It 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.[15] 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.[16][17] Butyric acid is present as its octyl ester in parsnip (Pastinaca sativa)[18] and in the seed of the ginkgo tree.[19] Production Industrial In industry, butyric acid is produced by hydroformylation from propene and syngas, forming butyraldehyde, which is oxidised to the final product.[7] H2 + CO + CH3CH=CH2 → CH3CH2CH2CHO → butyric acid 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. Microbial biosynthesis 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. Butyrate is produced by several fermentation processes performed by obligate anaerobic bacteria.[20] This fermentation pathway was discovered by Louis Pasteur in 1861. Examples of butyrate-producing species of bacteria: Clostridium butyricum Clostridium kluyveri Clostridium pasteurianum Faecalibacterium prausnitzii Fusobacterium nucleatum Butyrivibrio fibrisolvens Eubacterium limosum 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 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: Clostridium acetobutylicum, the most prominent acetone and butanol producer, used also in industry Clostridium beijerinckii Clostridium tetanomorphum Clostridium aurantibutyricum 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 sources 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.[14][21] One study found that resistant starch consistently produces more butyrate than other types of dietary fiber.[22] The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.[13][23] Fructans are another source of prebiotic soluble dietary fibers which can be digested to produce butyrate.[24] 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),[25] 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.[26][27] Reactions Butyric acid reacts as a typical carboxylic acid: it can form amide, ester, anhydride, and chloride derivatives.[28] The latter, butyryl chloride is commonly used as the intermediate to obtain the others. Uses 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, paints, and coatings, and is more resistant to degradation than cellulose acetate.[29] However, CAB can degrade with exposure to heat and moisture, releasing butyric acid.[30] 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.[31] 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.[32] The substance has also been used as a stink bomb by Sea Shepherd Conservation Society to disrupt Japanese whaling crews.[33] Pharmacology Human enzyme and GPCR binding[34][35] 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 Pharmacodynamics Butyric acid (pKa 4.82) is fully ionized at physiological pH, so its anion is the material that is mainly relevant in biological systems. It 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),[16][17] 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; however, among the group of SCFAs, only butyrate is an agonist of HCA2.[36][37][38] It is also an HDAC inhibitor (specifically, HDAC1, HDAC2, HDAC3, and HDAC8),[34][35] a drug that inhibits the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in cells.[38] Histone acetylation loosens the structure of chromatin by reducing the electrostatic attraction between histones and DNA.[38] 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,[38] which are typically silenced or downregulated due to histone deacetylase activity. Pharmacokinetics 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; 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.[38] 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).[39][40] Other transporters that mediate the passage of butyrate across lipid membranes include SLC5A8 (SMCT1), SLC27A1 (FATP1), and SLC27A4 (FATP4).[34][40] Metabolism Butyric acid is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase.[41][42] The metabolite produced by this reaction is butyryl–CoA, and is produced as follows:[41] 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.[38] In particular, it is an important energy source for cells lining the mammalian colon (colonocytes).[24] Without butyrates, colon cells undergo autophagy (i.e., self-digestion) and die.[43] In humans, the butyrate precursor tributyrin, which is naturally present in butter, is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:[44] Tributyrin + H2O → dibutyrin + butyric acid Biochemistry 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. 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).[36][45] In the mammalian gut Butyrate is essential to host immune homeostasis.[36] Although the role and importance of butyrate in the gut is not fully understood, many researchers argue that a depletion of butyrate-producing bacteria in patients with several vasculitic conditions is essential to the pathogenesis of these disorders. A depletion of butyrate in the gut is typically caused by an absence or depletion of butyrate-producing-bacteria (BPB). This depletion in BPB leads to microbial dysbiosis. This is characterized by an overall low biodiversity and a depletion of key butyrate-producing members. Butyrate is an essential microbial metabolite with a vital role as a modulator of proper immune function in the host. It has been shown that children lacking in BPB are more susceptible to allergic disease[46] and Type 1 Diabetes.[47] Butyrate exerts a key role for the maintenance of immune homeostasis both locally (in the gut) and systemically (via circulating butyrate). It has been shown to promote the differentiation of regulatory T cells. In particular, circulating butyrate prompts the generation of extrathymic regulatory T cells. The low-levels of butyrate in human subjects could favor reduced regulatory T cell-mediated control, thus promoting a powerful immuno-pathological T-cell response.[48] On the other hand, gut butyrate has been reported to inhibit local pro-inflammatory cytokines. The absence or depletion of these BPB in the gut could therefore be a possible aide in the overly-active inflammatory response. Butyrate in the gut also protects the integrity of the intestinal epithelial barrier. Decreased butyrate levels therefore lead to a damaged or dysfunctional intestinal epithelial barrier.[49] In a 2013 research study conducted by Furusawa et al, microbe-derived butyrate was found to be essential in inducing the differentiation of colonic regulatory T cells in mice. This is of great importance and possibly relevant to the pathogenesis and vasculitis associated with many inflammatory diseases because regulatory T cells have a central role in the suppression of inflammatory and allergic responses.[50] In several research studies, it has been demonstrated that butyrate induced the differentiation of regulatory T cells in vitro and in vivo.[51] The anti-inflammatory capacity of butyrate has been extensively analyzed and supported by many studies. It has been found that microorganism-produced butyrate expedites the production of regulatory T cells, although the specific mechanism by which it does so unclear.[52] More recently, it has been shown that butyrate plays an essential and direct role in modulating gene expression of cytotoxic T-cells.[53] Butyrate also has an anti-inflammatory effect on neutrophils, reducing their migration to wounds. This effect is mediated via the receptor HCA1[54] Immunomodulation and inflammation 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).[37][55] 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.[37] 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.[55][56][57] 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;[37][55] through these actions, it increases the expression of interleukin 10, an anti-inflammatory cytokine.[55][37] Butyrate also suppresses colonic inflammation by inhibiting the IFN-γ–STAT1 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.[58] 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.[59][60][61] Butyrate binding at FFAR3 induces neuropeptide Y release and promotes the functional homeostasis of colonic mucosa and the enteric immune system.[62] Cancer Butyrate has been shown to be a critical mediator of the colonic inflammatory response. It is responsible for about 70% of energy from the colonocytes, being a critical SCFA in colon homeostasis.[63] Butyrate possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis (UC) and colorectal cancer.[64] It 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.[65][66]The explanation why butyrate is an energy source for normal colonocytes and induces apoptosis in colon cancer cells, is the Warburg effect in cancer cells, which leads to butyrate not being properly metabolized. This phenomenon leads to the accumulation of butyrate in the nucleus, acting as a histone deacetylase (HDAC) inhibitor.[67] One mechanism underlying butyrate function in suppression of colonic inflammation is inhibition of the IFN-γ/STAT1 signalling pathways. 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 upregulation of Fas receptor on the T cell surface. 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).[68] Butyrate inhibits angiogenesis by inactivating Sp1 transcription factor activity and downregulating vascular endothelial growth factor gene expression.[69] In summary, the production of volatile fatty acids such as butyrate from fermentable fibers may contribute to the role of dietary fiber in colon cancer. 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.[21] Conversely, some researchers have sought to eliminate butyrate and consider it a potential cancer driver.[70] Studies in mice indicate it drives transformation of MSH2-deficient colon epithelial cells.[71] Potential treatments from butyrate restoration Owing to the importance of butyrate as an inflammatory regulator and immune system contributor, butyrate depletions could be a key factor influencing the pathogenesis of many vasculitic conditions. It is thus essential to maintain healthy levels of butyrate in the gut. Fecal microbiota transplants (to restore BPB and symbiosis in the gut) could be effective by replenishing butyrate levels. In this treatment, a healthy individual donates their stool to be transplanted into an individual with dysbiosis. A less-invasive treatment option is the administration of butyrate—as oral supplements or enemas—which has been shown to be very effective in terminating symptoms of inflammation with minimal-to-no side-effects. In a study where patients with ulcerative colitis were treated with butyrate enemas, inflammation decreased significantly, and bleeding ceased completely after butyrate provision.[72] Addiction Butyric acid is an HDAC inhibitor that is selective for class I HDACs in humans.[34] 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. Class I HDACs are known to be involved in mediating the development of an addiction.[73][74][75] 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.[75][76][77] Butyrate salts and esters The butyrate or butanoate, ion is C2H5COO−, the conjugate base of butyric acid. It is the form found in biological systems at physiological pH. A butyric, or butanoic, compound is a carboxylate salt or ester of butyric acid. Examples Salts Sodium butyrate Esters Butyl butyrate Butyryl-CoA Cellulose acetate butyrate (aircraft dope) Estradiol benzoate butyrate Ethyl butyrate Methyl butyrate Pentyl butyrate Tributyrin See also List of saturated fatty acids Histone Histone-modifying enzyme Histone acetylase Histone deacetylase Hydroxybutyric acids α-Hydroxybutyric acid β-Hydroxybutyric acid γ-Hydroxybutyric acid β-Methylbutyric acid β-Hydroxy β-methylbutyric acid Notes Most of the butyrate that is absorbed into blood plasma from the colon enters the circulatory system via the portal vein; most of the butyrate that enters the circulatory system by this route is taken up by the liver.[38] References This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). "Butyric Acid". Encyclopædia Britannica (11th ed.). Cambridge University Press. 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. Strieter FJ, Templeton DH (1962). "Crystal structure of butyric acid" (PDF). Acta Crystallographica. 15 (12): 1240–1244. doi:10.1107/S0365110X6200328X. Lide, David R., ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0. 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 27 October 2020) "Butanoic acid". Chemister.ru. 19 March 2007. Retrieved 27 October 2020. Sigma-Aldrich Co., Butyric acid. Retrieved on 27 October 2020. Riemenschneider, Wilhelm (2002). "Carboxylic Acids, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a05_235. 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. 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", … ) 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. Woo, A.H.; Lindsay, R.C. (1983). "Stepwise Discriminant Analysis of Free Fatty Acid Profiles for Identifying Sources of Lipolytic Enzymes in Rancid Butter". Journal of Dairy Science. 66 (10): 2070–2075. doi:10.3168/jds.S0022-0302(83)82052-9. ICSC 1334 – Butyric acid. Inchem.org (23 November 1998). Retrieved on 2020-10-27. 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. 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. "Butyric acid". The Good Scents Company. Retrieved 26 October 2020. 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. 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. 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. S2CID 23512190. 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. 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. 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. 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. 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. Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc (2016). "Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut". Frontiers in Microbiology. 7: 979. doi:10.3389/fmicb.2016.00979. PMC 4923077. PMID 27446020. "Frequently asked questions in the area of diet and IBS". Department of Gastroenterology Translational Nutrition Science, Monash University, Victoria, Australia. Retrieved 24 March 2016. 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. S2CID 20666740. 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. Jenkins, P. R. (1985). "Carboxylic acids and derivatives". General and Synthetic Methods. 7. pp. 96–160. doi:10.1039/9781847556196-00096. ISBN 978-0-85186-884-4. Lokensgard, Erik (2015). Industrial Plastics: Theory and Applications (6th ed.). Cengage Learning. Williams, R. Scott. "Care of Plastics: Malignant plastics". WAAC Newsletter. 24 (1). Conservation OnLine. Retrieved 29 May 2017. Freezer Baits Archived 25 January 2010 at the Wayback Machine, nutrabaits.net 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. Japanese Whalers Injured by Acid-Firing Activists Archived 8 June 2010 at the Wayback Machine, newser.com, 10 February 2010 "Butyric acid". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 13 July 2018. "Butanoic acid and Sodium butyrate". BindingDB. The Binding Database. Retrieved 27 October 2020. 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. 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. 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. 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. 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.