4498 Propionic acid Propionic acid (PA) is a short chain fatty acid (SCFA) that is produced by bacterial (or gut) fermentation of fiber and sugars. The human skin is host of several species of bacteria known as Propionibacteria, which are named after their ability to produce propionic acid. The most notable one is the Propionibacterium acnes, which lives mainly in the sebaceous glands of the skin and is one of the principal causes of acne. Propionic acid can also play a role in carboxylic acid metabolism. In particular, propionyl coenzyme A (propionyl-CoA), is the first step in the process. Because propionic acid has three carbons (instead of two), propionyl-CoA cannot directly enter either beta oxidation or the citric acid cycles. In addition to its role in basic biochemistry, propionic acid is widely used as an antifungal agent in food. It is present naturally at low levels in dairy products and occurs ubiquitously, together with other short-chain fatty acids (SCFA), in the gastro-intestinal tract of humans and other mammals as an end-product of the microbial digestion of carbohydrates. It has significant physiological activity in animals. PA is a known irritant but produces no acute systemic effects and has no demonstrable genotoxic potential (PMID 1628870). When present in sufficiently high levels, propionic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of propionic acid are associated with Propionic acidemia and aciduria. Propionic aciduria is one of the most frequent organic acidurias. Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. Those who survive past infancy generally have poor intellectual development patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not prevented neurological and various visceral complications. Decreased early mortality, less severe symptoms at diagnosis, and more favorable short-term neurodevelopmental outcome were recorded in patients identified through expanded newborn screening. (PMID 16763906). Propionic acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, kidney and liver abnormalities, seizures, coma, and possibly death. These are some of the characteristic symptoms of untreated Propionic acidemia. Many affected children with organic acidemias experience intellectual disability or delayed development. When propionic acid is infused directly into rodents' brains, it produces reversible behaviour (e.g., hyperactivity, dystonia, social impairment, perseveration) and brain changes (e.g., innate neuroinflammation, glutathione depletion). 79-09-4 1032 C3H6O2 -20.7°C 140.99°C (285.8°F) 1000.0 mg/mL In healthy individuals, the enzyme propionyl CoA carboxylase converts propionyl CoA to methylmalonyl CoA. This is one step in the process of converting certain amino acids and fats into sugar for energy. Individuals with propionic acidemia cannot perform this conversion because the enzyme propionyl CoA carboxylase is nonfunctional. The essential amino acids; isoleucine, valine, threonine, and methionine and odd-chain fatty acids are simply converted to propionyl CoA, before the process stops, leading to a buildup of propionyl CoA. Instead of being converted to methylmalonyl CoA, propionyl CoA is then converted into propionic acid, which builds up in the bloodstream. Propionyl-CoA, propionic acid, ketones, ammonia, and other toxic compounds accumulate in the blood, causing the signs and symptoms of propionic acidemia. Propionate acts as a metabolic toxin in liver cells by accumulating in mitochondria. Propanoate is metabolized oxidatively by glia, which suggests astrocytic vulnerability in propanoic acidemia when intramitochondrial propionyl-CoA may accumulate. Propanoic acidemia may alter both neuronal and glial gene expression by affecting histone acetylation (A15452, A15453). (Wikipedia) The metabolism of propanoic acid begins with its conversion to propionyl coenzyme A (propionyl-CoA), the usual first step in the metabolism of carboxylic acids. Since propanoic 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. (Wikipedia) No indication of carcinogenicity to humans (not listed by IARC). This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation. Propionic acid occurs in chronically high levels in propionic acidemia. Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, is an autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia. The disorder presents in the early neonatal period with progressive encephalopathy. Death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or basal ganglial stroke. In many cases, propionic acidemia can damage the brain, heart, and liver, cause seizures, and delays to normal development like walking and talking. (Wikipedia) Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening. (Wikipedia) During times of illness the affected person may need to be hospitalized to prevent breakdown of proteins within the body. Each meal presents a challenge to those with propionic acidemia. If not constantly monitored, the effects would be devastating. Dietary needs must be closely managed by a metabolic geneticist or metabolic dietician. Patients with propionic acidemia should be started as early as possible on a low protein diet. In addition to a protein mixture that is devoid of methionine, threonine, valine, and isoleucine, the patient should also receive L-carnitine treatment and should be given antibiotics 10 days per month in order to remove the intestinal propiogenic flora. The patient should have diet protocols prepared for him with a “well day diet” with low protein content, a “half emergency diet” containing half of the protein requirements, and an “emergency diet” with no protein content. These patients are under the risk of severe hyperammonemia during infections that can lead to comatose states. Liver transplant is gaining a role in the management of these patients, with small series showing improved quality of life. (Wikipedia) 2014-08-29T06:51:18Z 2018-03-21T17:46:16Z Propionic acid C00163 30768 PROPIONATE DB03766 PPI true CCC(O)=O C3H6O2 InChI=1S/C3H6O2/c1-2-3(4)5/h2H2,1H3,(H,4,5) InChIKey=XBDQKXXYIPTUBI-UHFFFAOYSA-N 74.0785 74.036779436 Endogenous Liquid 0.33 HMDB00237 CHEMBL14021 1005 <p>James R. Hazen, &#8220;Process for production of 3-(hydroxyphenylphosphinyl)-propanoic acid.&#8221; U.S. Patent US4769182, issued March, 1978.</p>