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 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 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 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.
ActionResponsible enzyme
Acetyl coenzyme A converts into acetoacetyl coenzyme Aacetyl-CoA-acetyl transferase
Acetoacetyl coenzyme A converts into β-hydroxybutyryl CoAβ-hydroxybutyryl-CoA dehydrogenase
β-hydroxybutyryl CoA converts into crotonyl CoAcrotonase
Crotonyl CoA converts into butyryl CoA butyryl CoA dehydrogenase
A phosphate group replaces CoA to form butyryl phosphatephosphobutyrylase
The phosphate group joins ADP to form ATP and butyratebutyrate 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.

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.