Butyric acid
Butyric acid, also known under the systematic name butanoic acid, is a straight-chain alkyl fatty acid with the chemical formula. It is an oily, colorless liquid with an unpleasant odor. Isobutyric 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 and an important component in the mammalian gut.
History
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. By 1817, he published some of his findings regarding the properties of butyric acid and named it. However, it was not until 1823 that he presented the properties of butyric acid in detail. The name butyric acid comes from, meaning "butter", the substance in which it was first found. The Latin name butyrum is similar.Occurrence
s of butyric acid make up 3–4% of butter. When butter goes rancid, butyric acid is liberated from the glyceride by hydrolysis. 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.It is found in animal fat and plant oils, bovine milk, papaya, breast milk, butter, parmesan cheese, body odor, and vomit as a product of anaerobic fermentation. 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.
In humans, butyric acid is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2, a G protein-coupled receptor.
Butyric acid is present as its Ester#List of [ester odorants|octyl ester] in parsnip and in the seed of the ginkgo tree.
Production
Industrial
In industry, butyric acid is produced by hydroformylation from propene and syngas, forming butyraldehyde, which is oxidised to the final product.It can be separated from aqueous solutions by saturation with salts such as calcium chloride. The calcium salt,, is less soluble in hot water than in cold.
Microbial biosynthesis
Butyrate is produced by several fermentation processes performed by obligate anaerobic bacteria. This fermentation pathway was discovered by Louis Pasteur in 1861. Examples of butyrate-producing species of bacteria:Clostridium butyricumClostridium kluyveriClostridium pasteurianumFaecalibacterium prausnitziiFusobacterium nucleatumButyrivibrio fibrisolvensEubacterium limosumThe 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 and two molecules of hydrogen are formed as waste products. Subsequently, 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
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 | 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 industryClostridium beijerinckiiClostridium tetanomorphumClostridium 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
The most common species used for probiotics is the Clostridium butyricum.
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 including butyrate, producing more SCFA than less fermentable fibers such as celluloses. One study found that resistant starch consistently produces more butyrate than other types of dietary fiber. The production of SCFA from fibers in ruminant animals such as cattle is responsible for the butyrate content of milk and butter.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, 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, oligofructose, and inulin.
Dietary patterns strongly influence colonic butyrate production, as certain foods contain high levels of fermentable fibres that are preferentially metabolized by butyrate-producing bacteria. Resistant starch–rich foods such as cooked-and-cooled potatoes, rice, and legumes substantially increase luminal butyrate concentrations compared with lower-fermentability fibres. Soluble fibres found in oats, barley β-glucans, pectin-rich fruits, and guar gum similarly enhance microbial butyrate formation.
Chemical reactions
Butyric acid reacts as a typical carboxylic acid: it can form amide, ester, anhydride, and chloride derivatives. 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, which is used in a wide variety of tools, paints, and coatings, and is more resistant to degradation than cellulose acetate. CAB can degrade with exposure to heat and moisture, releasing butyric acid.Low-molecular-weight esters of butyric acid, such as methyl butyrate, have mostly pleasant aromas or tastes. As a consequence, they are used as food and perfume additives. It is an approved food flavoring in the EU FLAVIS database.
Due to its powerful odor, it has also been used as a fishing bait additive. Many of the commercially available flavors used in carp 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.
The substance has been used as a stink bomb by the Sea Shepherd Conservation Society to disrupt Japanese whaling crews. The Dutch branch of Extinction Rebellion has used it as a chemical agent in a clothing store; several people who became unwell were treated on site by an ambulance crew.
Pharmacology
Pharmacodynamics
Butyric acid 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, a G protein-coupled receptor,
Like other short-chain fatty acids, 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. It is also an HDAC inhibitor, a drug that inhibits the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in cells.
Pharmacokinetics
Butyrate that is produced in the colon through microbial fermentation of dietary fiber is primarily absorbed and metabolized by colonocytes and the liver 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. Butyrate that has reached systemic circulation can readily cross the blood–brain barrier via monocarboxylate transporters. Other transporters that mediate the passage of butyrate across lipid membranes include SLC5A8, SLC27A1, and SLC27A4.Metabolism
Butyric acid is metabolized by various human XM-ligases, also known as butyrate–CoA ligase. The metabolite produced by this reaction is butyryl–CoA, and is produced as follows:As a short-chain fatty acid, butyrate is metabolized by mitochondria as an energy source through fatty acid metabolism. In particular, it is an important energy source for cells lining the mammalian colon. Without butyrates, colon cells undergo autophagy and die.
In humans, the butyrate precursor tributyrin, which is naturally present in butter, is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction:
Biochemistry
Butyrate has numerous effects on energy homeostasis in humans. These effects occur through its metabolism by mitochondria to generate during fatty acid metabolism or through one or more of its histone-modifying enzyme targets and G-protein coupled receptor targets.Mammalian gut
Butyrate is essential to host immune homeostasis. Although the role and importance of butyrate in the gut is not settled, 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. 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 and type 1 diabetes. 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.Decreased butyrate levels lead to a damaged or dysfunctional intestinal epithelial barrier. 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.
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.
The odor of butyric acid, which emanates from the sebaceous follicles of all mammals, works on ticks as a signal.