Propionic acid

Propionic acid was first described in 1844 by Johann Gottlieb, who found it among the degradation products of sugar.[10] Over the next few years, other chemists produced propionic acid in various other ways, none of them realizing they were producing the same substance. In 1847, the French chemist Jean-Baptiste Dumas established all the acids to be the same compound, which he called propionic acid, from the Greek words πρῶτος (prōtos), meaning first, and πίων (piōn), meaning fat, because it is the smallest H(CH₂)_nCOOH acid that exhibits the properties of the other fatty acids, such as producing an oily layer when salted out of water and having a soapy potassium salt.[11]

Propionic acid has physical properties intermediate between those of the smaller carboxylic acids, formic and acetic acids, and the larger fatty acids. It is miscible with water, but can be removed from water by adding salt. As with acetic and formic acids, it consists of hydrogen bonded pairs of molecules as both the liquid and the vapor.

Propionic acid displays the general properties of carboxylic acids: it can form amide, ester, anhydride, and chloride derivatives. It undergoes the Hell–Volhard–Zelinsky reaction that involves α-halogenation of a carboxylic acid with bromine, catalysed by phosphorus tribromide, in this case to form 2-bromopropanoic acid, CH₃CHBrCOOH.[12] This product has been used to prepare a racemic mixture of alanine by ammonolysis.[13][14]

In industry, propionic acid is mainly produced by the hydrocarboxylation of ethylene using nickel carbonyl as the catalyst:[15]

H₂C=CH₂ + H₂O + CO → CH₃CH₂CO₂H

It is also produced by the aerobic oxidation of propionaldehyde. In the presence of cobalt or manganese ions, this reaction proceeds rapidly at temperatures as mild as 40–50 °C:

CH₃CH₂CHO + ​¹⁄₂ O₂ → CH₃CH₂COOH.

Large amounts of propionic acid were once produced as a byproduct of acetic acid manufacture. At the current time, the world's largest producer of propionic acid is BASF, with approximately 150 kt/a production capacity.

Propionic acid is produced biologically as its coenzyme A ester, propionyl-CoA, from the metabolic breakdown of fatty acids containing odd numbers of carbon atoms, and also from the breakdown of some amino acids. Bacteria of the genus Propionibacterium produce propionic acid as the end-product of their anaerobic metabolism. This class of bacteria is commonly found in the stomachs of ruminants and the sweat glands of humans, and their activity is partially responsible for the odor of both Swiss cheese and sweat.

Biotechnological production of propionic acid is mainly studied by the use of Propionibacterium strains. However, production of propionic acid by Propionibacteria is facing challenges such as severe inhibition of end-products during cell growth and the formation of by-products (acetic acid and succinic acid).[16] One approach to improve productivity and yield during fermentation is through the use of cell immobilization techniques, which also promotes easy recovery, reuse of the cell biomass and enhances microorganisms’ stress tolerance.[17] In 2018, 3D printing technology was used for the first time to create a matrix for cell immobilization in fermentation. Propionic acid production by Propionibacterium acidipropionici immobilized on 3D-printed nylon beads was chosen as a model study. It was shown that those 3D-printed beads were capable to promote high density cell attachment and propionic acid production, which could be adapted to other fermentation bioprocesses.[18] Other cell immobilization matrices have been tested, such as recycled-glass Poraver and fibrous-bed bioreactor.[19][20]

It is also biosynthesized in the large intestine of humans by bacterial fermentation of dietary fibre.[21]

Propionic acid inhibits the growth of mold and some bacteria at the levels between 0.1 and 1% by weight. As a result, most propionic acid produced is consumed as a preservative for both animal feed and food for human consumption. For animal feed, it is used either directly or as its ammonium salt. The antibiotic Monensin is added to cattle feed to favor propionibacteria over acetic acid producers in the rumen; this produces less carbon dioxide and feed conversion is better. This application accounts for about half of the world production of propionic acid. Another major application is as a preservative in baked goods, which use the sodium and calcium salts.[15] As a food additive, it is approved for use in the EU,[22] USA[23] and Australia and New Zealand.[24] It is listed by its INS number (280) or E number E280.

Propionic acid is also useful as an intermediate in the production of other chemicals, especially polymers. Cellulose-acetate-propionate is a useful thermoplastic. Vinyl propionate is also used. In more specialized applications, it is also used to make pesticides and pharmaceuticals. The esters of propionic acid have fruit-like odors and are sometimes used as solvents or artificial flavorings.[15]

In biogas plants, propionic acid is a common intermediate product, which is formed by fermentation with propionic acid bacteria. Its degradation in anaerobic environments (e.g. biogas plants) requires the activity of complex microbial communities.[25]

The metabolism of propionic acid begins with its conversion to propionyl coenzyme A (propionyl-CoA), the usual first step in the metabolism of carboxylic acids. Since propionic acid has three carbons, propionyl-CoA cannot directly enter either beta oxidation or the citric acid cycles. In most vertebrates, propionyl-CoA is carboxylated to D-methylmalonyl-CoA, which is isomerised to L-methylmalonyl-CoA. A vitamin B₁₂-dependent enzyme catalyzes rearrangement of L-methylmalonyl-CoA to succinyl-CoA, which is an intermediate of the citric acid cycle and can be readily incorporated there.

In propionic acidemia, a rare inherited genetic disorder, propionate acts as a metabolic toxin in liver cells by accumulating in mitochondria as propionyl-CoA and its derivative, methylcitrate, two tricarboxylic acid cycle inhibitors. Propanoate is metabolized oxidatively by glia, which suggests astrocytic vulnerability in propionic acidemia when intramitochondrial propionyl-CoA may accumulate. Propionic acidemia may alter both neuronal and glial gene expression by affecting histone acetylation.[26][27] When propionic acid is infused directly into rodents' brains, it produces reversible behavior (e.g., hyperactivity, dystonia, social impairment, perseveration) and brain changes (e.g., innate neuroinflammation, glutathione depletion) that may be used as a means to model autism in rats.[26]

It also, being a three-carbon molecule, feeds into hepatic gluconeogenesis (that is, the creation of glucose molecules from simpler molecules in the liver).[28]

• List of saturated fatty acids

Wikimedia Commons has media related to Propionic acid.

• NIST Standard Reference Database
• International Chemical Safety Card 0806
• NIOSH Pocket Guide to Chemical Hazards
• Technical data of propionic acid of BASF
• Neurobiological effects of intraventricular propionic acid in ratsPossible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders
• The Propionic Acids. Gastrointestinal Toxicity in Various Species
• Propionic Acid Technical Data Sheet