Butyric acid

Template:Short description Template:Use dmy dates Template:Chembox

Butyric acid (Template:IPAc-en; from Template:Langx, meaning "butter"), also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula Template:Chem2. 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<ref name=Ullmann>Template:Ullmann</ref> and an important component in the mammalian gut.

HistoryEdit

Butyric acid was first observed in an 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, another 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.<ref>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 pp. 75–76, he mentions that he had found a substance that is responsible for the smell of butter.</ref> By 1817, he published some of his findings regarding the properties of butyric acid and named it.<ref>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", … )</ref> However, it was not until 1823 that he presented the properties of butyric acid in detail.<ref>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.</ref> The name butyric acid comes from Template:Wikt-lang, meaning "butter", the substance in which it was first found. The Latin name butyrum (or buturum) is similar.

OccurrenceEdit

Triglycerides of butyric acid make up 3–4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis.<ref>Template:Cite journal</ref> 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.<ref name="inchem1">ICSC 1334 – Butyric acid. Inchem.org (23 November 1998). Retrieved on 2020-10-27.</ref> 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).<ref name="mcnabney">Template:Cite journal</ref><ref name="morrison">Template:Cite journal</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In humans, butyric acid is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2 (Template:Chem2), a Template:Nowrap G protein-coupled receptor.<ref name="IUPHAR's comprehensive 2011 review on HCARs">Template:Cite journal</ref><ref name="IUPHAR-DB HCAR family page">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Butyric acid is present as its octyl ester in parsnip (Pastinaca sativa)<ref>Template:Cite journal </ref> and in the seed of the ginkgo tree.<ref>Template:Cite book</ref>

ProductionEdit

IndustrialEdit

In industry, butyric acid is produced by hydroformylation from propene and syngas, forming butyraldehyde, which is oxidised to the final product.<ref name=Ullmann/>

Template:Chem2 Template:Oversetbutyric acid

It can be separated from aqueous solutions by saturation with salts such as calcium chloride. The calcium salt, Template:Chem2, is less soluble in hot water than in cold.

Microbial biosynthesisEdit

File:ButyrateBisyn.svg

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.<ref>Template:Cite journal </ref> 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 (Template:Chem2) and two molecules of hydrogen (Template:Chem2) are formed as waste products. Subsequently, Template:Abbr 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

Template:Chem2

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 (Template:Chem2)	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

For commercial purposes Clostridium species are used preferably for butyric acid or butanol production. The most common species used for probiotics is the Clostridium butyricum.<ref>Template:Cite journal</ref>

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.<ref name=morrison/><ref name="lupton">Template:Cite journal</ref> One study found that resistant starch consistently produces more butyrate than other types of dietary fiber.<ref>Template:Cite journal</ref> The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.<ref name=mcnabney/><ref>Template:Cite journal</ref>

Fructans are another source of prebiotic soluble dietary fibers which can be digested to produce butyrate.<ref name="pmc4923077">Template:Cite journal</ref> 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),<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

ReactionsEdit

Butyric acid reacts as a typical carboxylic acid: it can form amide, ester, anhydride, and chloride derivatives.<ref>Template:Cite book</ref> The latter, butyryl chloride, is commonly used as the intermediate to obtain the others.

UsesEdit

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.<ref>Template:Cite book Template:ISBN?Template:Page?</ref> CAB can degrade with exposure to heat and moisture, releasing butyric acid.<ref>Template:Cite news</ref>

Low-molecular-weight esters of butyric acid, such as methyl butyrate, have mostly pleasant aromas or tastes.<ref name=Ullmann/> 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.<ref>Freezer Baits Template:Webarchive, nutrabaits.net</ref> Many of the commercially available flavors used in carp (Cyprinus carpio) baits use butyric acid as their ester base. It is not clear whether fish are attracted by the butyric acid itself or the substances added to it. Butyric acid was one of the few organic acids shown to be palatable for both tench and bitterling.<ref>Template:Cite journal</ref> The substance has been used as a stink bomb by the Sea Shepherd Conservation Society to disrupt Japanese whaling crews.<ref>Japanese Whalers Injured by Acid-Firing Activists Template:Webarchive, newser.com, 10 February 2010</ref>

The Dutch branch of Extinction Rebellion has used it as a chemical agent in a clothing store.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

PharmacologyEdit

citation
GPCR target	pEC₅₀	Entry note
CitationClass=web }}</ref><ref name="BindingDB">{{#invoke:citation/CS1\|citation	CitationClass=web }}</ref>	Inhibited enzyme	IC₅₀ (Template:Abbr)	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
FFAR2	2.9–4.6	Full agonist
FFAR3	3.8–4.9	Full agonist
[[Hydroxycarboxylic acid receptor 2\|Template:Chem2]]	2.8	Agonist

PharmacodynamicsEdit

Butyric acid (pK_a 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 (Template:Chem2, also known as GPR109A), a Template:Nowrap G protein-coupled receptor (GPCR),<ref name="IUPHAR's comprehensive 2011 review on HCARs" /><ref name="IUPHAR-DB HCAR family page" />

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.<ref name="Review – General summary as of April 2015" /><ref name="Review butyrate human T-cell HDACs" /><ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review">Template:Cite journal</ref> It is also an HDAC inhibitor (specifically, HDAC1, HDAC2, HDAC3, and HDAC8),<ref name="IUPHAR" /><ref name="BindingDB" /> a drug that inhibits the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in cells.<ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review" /> Histone acetylation loosens the structure of chromatin by reducing the electrostatic attraction between histones and DNA.<ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review" /> 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).Template:Medcn Therefore, butyric acid is thought to enhance the transcriptional activity at promoters,<ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review" /> which are typically silenced or downregulated due to histone deacetylase activity.

PharmacokineticsEdit

Butyrate that is produced in the colon through microbial fermentation of dietary fiber is primarily absorbed and metabolized by colonocytes and the liver<ref group="note">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.<ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review" /></ref> 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.<ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review" /><ref>Template:Cite journal</ref> 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).<ref name="SCFA MCT-mediated BBB passage – 2005 review">Template:Cite journal</ref><ref name="SCFA MCT-mediated BBB passage – 2014 review">Template:Cite journal</ref> Other transporters that mediate the passage of butyrate across lipid membranes include SLC5A8 (SMCT1), SLC27A1 (FATP1), and SLC27A4 (FATP4).<ref name="IUPHAR" /><ref name="SCFA MCT-mediated BBB passage – 2014 review" />

Metabolism Template:AnchorEdit

Butyric acid is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase.<ref name="HMDB">Template:Cite encyclopedia</ref><ref name="Butyrate metabolism">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The metabolite produced by this reaction is butyryl–CoA, and is produced as follows:<ref name="HMDB" />

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.<ref name="Butyrate pharmacodynamics and neuroepigenetic effects 2016 review" /> In particular, it is an important energy source for cells lining the mammalian colon (colonocytes).<ref name=pmc4923077/> Without butyrates, colon cells undergo autophagy (i.e., self-digestion) and die.<ref>Template:Cite journal</ref>

In humans, the butyrate precursor tributyrin, which is naturally present in butter, is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:<ref name="BRENDA tributyrin">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Tributyrin + Template:Chem2 dibutyrin + butyric acid

Template:Clear right

BiochemistryEdit

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 Template:Abbr 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 [[Hydroxycarboxylic acid receptor 2|Template:Chem2]]).<ref name="Review – General summary as of April 2015">Template:Cite journal</ref><ref name="Review for diabetes">Template:Cite journal</ref>

In the mammalian gutEdit

Butyrate is essential to host immune homeostasis.<ref name="Review – General summary as of April 2015" /> 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<ref>Template:Cite journal</ref> and Type 1 Diabetes.<ref>Template:Cite journal</ref> Butyrate is also reduced in a diet low in dietary fiber, which can induce inflammation and have other adverse affects insofar as these short-chain fatty acids activate PPAR-γ.<ref name="pmid32623619">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> Butyrate reduction has also been associated with Clostridioides difficile proliferation. Conversely, a high-fiber diet results in higher butyric acid concentration and inhibition of C. difficile growth.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> In several research studies, it has been demonstrated that butyrate induced the differentiation of regulatory T cells in vitro and in vivo.<ref>Template:Cite journal</ref> 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 is unclear.<ref>Template:Cite journal</ref> More recently, it has been shown that butyrate plays an essential and direct role in modulating gene expression of cytotoxic T-cells.<ref>Template:Cite journal</ref> Butyrate also has an anti-inflammatory effect on neutrophils, reducing their migration to wounds. This effect is mediated via the receptor [[Hydroxycarboxylic acid receptor 1|Template:Chem2]].<ref>Template:Cite journal</ref>

In the gut microbiomes found in the class Mammalia, omnivores and herbivores have butyrate-producing bacterial communities dominated by the butyryl-CoA:acetate CoA-transferase pathway, whereas carnivores have butyrate-producing bacterial communities dominated by the butyrate kinase pathway.<ref>Template:Cite journal</ref>

The odor of butyric acid, which emanates from the sebaceous follicles of all mammals, works on ticks as a signal.

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: [[Hydroxycarboxylic acid receptor 2|Template:Chem2]] (GPR109A), FFAR2 (GPR43), and FFAR3 (GPR41).<ref name="Review butyrate human T-cell HDACs" /><ref name="REVIEW butyrate human LL-37" /> 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 Template:Chem2 ligand.<ref name="Review butyrate human T-cell HDACs" /> 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.<ref name="REVIEW butyrate human LL-37">Template:Cite journal
Table 3: Select human antimicrobial peptides and their proposed targets
Table 4: Some known factors that induce antimicrobial peptide expression</ref><ref name="Primary – Butyrate and LL-37 target">Template:Cite journal</ref><ref name="Primary – LL-37 human pylori">Template:Cite journal</ref> In vitro, butyrate increases gene expression of FOXP3 (the transcription regulator for Template:Abbr) and promotes colonic regulatory T cells (Tregs) through the inhibition of class I histone deacetylases;<ref name="Review butyrate human T-cell HDACs" /><ref name="REVIEW butyrate human LL-37" /> through these actions, it increases the expression of interleukin 10, an anti-inflammatory cytokine.<ref name="REVIEW butyrate human LL-37" /><ref name="Review butyrate human T-cell HDACs">Template:Cite journal
Figure 1: Microbial-derived molecules promote colonic Treg differentiation.</ref> 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.<ref name="pmid22517765">Template:Cite journal</ref>

Similar to other Template:Chem2 agonists studied, butyrate also produces marked anti-inflammatory effects in a variety of tissues, including the brain, gastrointestinal tract, skin, and vascular tissue.<ref name="Niacin neuroinflammation">Template:Cite journal</ref><ref name="Niacin vascular inflammation">Template:Cite journal</ref><ref name="HCA2 anti-inflammatory effects">Template:Cite journal</ref> Butyrate binding at FFAR3 induces neuropeptide Y release and promotes the functional homeostasis of colonic mucosa and the enteric immune system.<ref name="Butyrate NPY review">Template:Cite journal</ref>

CancerEdit

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.<ref>Template:Cite journal</ref> Butyrate possesses both preventive and therapeutic potential to counteract inflammation-mediated ulcerative colitis (UC) and colorectal cancer.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> 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).<ref>Template:Cite journal</ref> Butyrate inhibits angiogenesis by inactivating Sp1 transcription factor activity and downregulating vascular endothelial growth factor gene expression.<ref>Template:Cite journal</ref>

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.<ref name="lupton"/>

Conversely, some researchers have sought to eliminate butyrate and consider it a potential cancer driver.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Studies in mice indicate it drives transformation of MSH2-deficient colon epithelial cells.<ref>Template:Cite journal</ref>

Potential treatments from butyrate restorationEdit

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.<ref>Template:Cite journal</ref>

AddictionEdit

Butyric acid is an Template:Abbrlink inhibitor that is selective for class I HDACs in humans.<ref name="IUPHAR" /> 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.<ref name="Nestler">Template:Cite journal</ref><ref name="Nestler 2014 epigenetics">Template:Cite journal</ref><ref name="Chromatin states">Template:Cite journal</ref> 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.<ref name="Chromatin states" /><ref name="pmid28255755">Template:Cite journal</ref><ref name="pmid28682229">Template:Cite journal</ref>

Butyrate salts and estersEdit

The butyrate or butanoate ion, Template:Chem2, is 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.

ExamplesEdit

SaltsEdit

Sodium butyrate

EstersEdit

Butyl butyrate
Butyryl-CoA
Cellulose acetate butyrate (aircraft dope)
Estradiol benzoate butyrate
Ethyl butyrate
Methyl butyrate
Pentyl butyrate
Tributyrin

NotesEdit

Template:Reflist

ReferencesEdit

{{#if: |

   |{{#ifeq: Butyric Acid |
                |{{#ifeq: |
                             |File:PD-icon.svg 
                             |File:Wikisource-logo.svg 
                           }}
                |File:Wikisource-logo.svg 
               }}
  }}{{#ifeq:  |
   |{{#ifeq:  |
                                    |This article
                                    |One or more of the preceding sentences
                                   }} incorporates text from a publication now in the public domain: 
  }}{{#invoke:template wrapper|{{#if:|list|wrap}}|_template=cite EB1911
   |_exclude=footnote, inline, noicon, no-icon, noprescript, no-prescript, _debug

   | noicon=1
  }}{{#ifeq:  ||}}

Template:Reflist Template:Reflist

External linksEdit

Template:Sister project

NIST Standard Reference Data for butanoic acid

Template:Fatty acids Template:HDAC inhibitors Template:GABA metabolism and transport modulators Template:Authority control