Relevant Data

Food Additives Approved in the United States:

Food Additives Approved by WHO:

  • PROPIONIC ACID [show]

General Information

Chemical namePropionic acid
CAS number79-09-4
COE number3
JECFA number84
Flavouring typesubstances
FL No.08.003
MixtureNo
Purity of the named substance at least 95% unless otherwise specified
Reference bodyJECFA

From webgate.ec.europa.eu

Computed Descriptors

Download SDF
2D Structure
CID1032
IUPAC Namepropanoic acid
InChIInChI=1S/C3H6O2/c1-2-3(4)5/h2H2,1H3,(H,4,5)
InChI KeyXBDQKXXYIPTUBI-UHFFFAOYSA-N
Canonical SMILESCCC(=O)O
Molecular FormulaC3H6O2
Wikipediapropionate

From Pubchem


Computed Properties

Property Name Property Value
Molecular Weight74.079
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count2
Rotatable Bond Count1
Complexity40.2
CACTVS Substructure Key Fingerprint A A A D c Y B A M A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A G g A A C A A A C A C A g A A C C A A A A g A I A A C Q C A A A A A A A A A A A A A E A A A A A A A A A A A A A Q A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area37.3
Monoisotopic Mass74.037
Exact Mass74.037
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count5
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem


Food Additives Biosynthesis/Degradation


ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9410
Human Intestinal AbsorptionHIA+0.9893
Caco-2 PermeabilityCaco2+0.6324
P-glycoprotein SubstrateNon-substrate0.7959
P-glycoprotein InhibitorNon-inhibitor0.9671
Non-inhibitor0.9909
Renal Organic Cation TransporterNon-inhibitor0.9624
Distribution
Subcellular localizationMitochondria0.5849
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7880
CYP450 2D6 SubstrateNon-substrate0.9394
CYP450 3A4 SubstrateNon-substrate0.8006
CYP450 1A2 InhibitorNon-inhibitor0.8922
CYP450 2C9 InhibitorNon-inhibitor0.9639
CYP450 2D6 InhibitorNon-inhibitor0.9667
CYP450 2C19 InhibitorNon-inhibitor0.9794
CYP450 3A4 InhibitorNon-inhibitor0.9763
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9876
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9681
Non-inhibitor0.9778
AMES ToxicityNon AMES toxic0.9401
CarcinogensCarcinogens 0.6548
Fish ToxicityLow FHMT0.5937
Tetrahymena Pyriformis ToxicityLow TPT0.8365
Honey Bee ToxicityHigh HBT0.7513
BiodegradationReady biodegradable0.9079
Acute Oral ToxicityIII0.9124
Carcinogenicity (Three-class)Non-required0.7073

From admetSAR


ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility0.6067LogS
Caco-2 Permeability1.1352LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity1.4864LD50, mol/kg
Fish Toxicity3.5551pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.6348pIGC50, ug/L

From admetSAR


Toxicity Profile

Route of Exposure
Mechanism of ToxicityIn 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 . (Wikipedia)
MetabolismThe 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)
Toxicity Values
Lethal Dose
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level
Health EffectsPropionic 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)
TreatmentDuring 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)
Reference
  1. Chandler RJ, Aswani V, Tsai MS, Falk M, Wehrli N, Stabler S, Allen R, Sedensky M, Kazazian HH, Venditti CP: Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism. Mol Genet Metab. 2006 Sep-Oct;89(1-2):64-73. Epub 2006 Jul 14.[16843692 ]
  2. Harrison PT: Propionic acid and the phenomenon of rodent forestomach tumorigenesis: a review. Food Chem Toxicol. 1992 Apr;30(4):333-40.[1628870 ]
  3. de Baulny HO, Benoist JF, Rigal O, Touati G, Rabier D, Saudubray JM: Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis. 2005;28(3):415-23.[15868474 ]
  4. Dionisi-Vici C, Deodato F, Roschinger W, Rhead W, Wilcken B: 'Classical' organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):383-9.[16763906 ]
  5. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7.[12097436 ]
  6. Somerma S, Lassus A, Salde L: Assessment of atrophy of human skin caused by corticosteroids using chamber occlusion and suction blister techniques. Acta Derm Venereol. 1984;64(1):41-5.[6203280 ]
  7. Marala RB, Brown JA, Kong JX, Tracey WR, Knight DR, Wester RT, Sun D, Kennedy SP, Hamanaka ES, Ruggeri RB, Hill RJ: Zoniporide: a potent and highly selective inhibitor of human Na(+)/H(+) exchanger-1. Eur J Pharmacol. 2002 Sep 6;451(1):37-41.[12223226 ]
  8. Lin SC, Bergles DE: Synaptic signaling between neurons and glia. Glia. 2004 Aug 15;47(3):290-8.[15252819 ]
  9. Alekseev OM, Widgren EE, Richardson RT, O'Rand MG: Association of NASP with HSP90 in mouse spermatogenic cells: stimulation of ATPase activity and transport of linker histones into nuclei. J Biol Chem. 2005 Jan 28;280(4):2904-11. Epub 2004 Nov 8.[15533935 ]
  10. Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN: Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr. 2005 Sep;82(3):559-67.[16155268 ]
  11. Esposito BP, Faljoni-Alario A, de Menezes JF, de Brito HF, Najjar R: A circular dichroism and fluorescence quenching study of the interactions between rhodium(II) complexes and human serum albumin. J Inorg Biochem. 1999 May 30;75(1):55-61.[10402677 ]
  12. Jeng JH, Chan CP, Ho YS, Lan WH, Hsieh CC, Chang MC: Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts. J Periodontol. 1999 Dec;70(12):1435-42.[10632518 ]
  13. Christensen JK, Varming T, Ahring PK, Jorgensen TD, Nielsen EO: In vitro characterization of 5-carboxyl-2,4-di-benzamidobenzoic acid (NS3763), a noncompetitive antagonist of GLUK5 receptors. J Pharmacol Exp Ther. 2004 Jun;309(3):1003-10. Epub 2004 Feb 25.[14985418 ]
  14. Bintvihok A, Kositcharoenkul S: Effect of dietary calcium propionate on performance, hepatic enzyme activities and aflatoxin residues in broilers fed a diet containing low levels of aflatoxin B1. Toxicon. 2006 Jan;47(1):41-6. Epub 2005 Nov 18.[16298407 ]
  15. Mayer B, Schumacher M, Brandstatter H, Wagner FS, Hermetter A: High-throughput fluorescence screening of antioxidative capacity in human serum. Anal Biochem. 2001 Oct 15;297(2):144-53.[11673881 ]
  16. De Kanter R, De Jager MH, Draaisma AL, Jurva JU, Olinga P, Meijer DK, Groothuis GM: Drug-metabolizing activity of human and rat liver, lung, kidney and intestine slices. Xenobiotica. 2002 May;32(5):349-62.[12065058 ]
  17. Ridge BD, Batt MD, Palmer HE, Jarrett A: The dansyl chloride technique for stratum corneum renewal as an indicator of changes in epidermal mitotic activity following topical treatment. Br J Dermatol. 1988 Feb;118(2):167-74.[3348963 ]
  18. Koeppe RA, Frey KA, Snyder SE, Meyer P, Kilbourn MR, Kuhl DE: Kinetic modeling of N-[11C]methylpiperidin-4-yl propionate: alternatives for analysis of an irreversible positron emission tomography trace for measurement of acetylcholinesterase activity in human brain. J Cereb Blood Flow Metab. 1999 Oct;19(10):1150-63.[10532640 ]
  19. Nguyen TB, Snyder SE, Kilbourn MR: Syntheses of carbon-11 labeled piperidine esters as potential in vivo substrates for acetylcholinesterase. Nucl Med Biol. 1998 Nov;25(8):761-8.[9863564 ]
  20. Wendel U, Zass R, Leupold D: Contribution of odd-numbered fatty acid oxidation to propionate production in neonates with methylmalonic and propionic acidaemias. Eur J Pediatr. 1993 Dec;152(12):1021-3.[8131803 ]
  21. Beutler KT, Pankewycz O, Brautigan DL: Equivalent uptake of organic and inorganic zinc by monkey kidney fibroblasts, human intestinal epithelial cells, or perfused mouse intestine. Biol Trace Elem Res. 1998 Jan;61(1):19-31.[9498328 ]
  22. MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, Taylor AR, Kavaliers M, Ossenkopp KP: Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[16950524 ]
  23. Nguyen NH, Morland C, Gonzalez SV, Rise F, Storm-Mathisen J, Gundersen V, Hassel B: Propionate increases neuronal histone acetylation, but is metabolized oxidatively by glia. Relevance for propionic acidemia. J Neurochem. 2007 May;101(3):806-14. Epub 2007 Feb 5.[17286595 ]

From T3DB


Taxonomic Classification

KingdomOrganic compounds
SuperclassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
SubclassCarboxylic acids
Intermediate Tree NodesNot available
Direct ParentCarboxylic acids
Alternative Parents
Molecular FrameworkAliphatic acyclic compounds
SubstituentsMonocarboxylic acid or derivatives - Carboxylic acid - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aliphatic acyclic compound
DescriptionThis compound belongs to the class of organic compounds known as carboxylic acids. These are compounds containing a carboxylic acid group with the formula -C(=O)OH.

From ClassyFire


Targets

General Function:
Molybdopterin molybdotransferase activity
Specific Function:
Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.
Gene Name:
GPHN
Uniprot ID:
Q9NQX3
Molecular Weight:
79747.635 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
General Function:
Lipid binding
Specific Function:
G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin-8/IL-8 in response to the presence of microbes (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016).
Gene Name:
FFAR2
Uniprot ID:
O15552
Molecular Weight:
37143.375 Da
References
  1. Wang Y, Jiao X, Kayser F, Liu J, Wang Z, Wanska M, Greenberg J, Weiszmann J, Ge H, Tian H, Wong S, Schwandner R, Lee T, Li Y: The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators. Bioorg Med Chem Lett. 2010 Jan 15;20(2):493-8. doi: 10.1016/j.bmcl.2009.11.112. Epub 2009 Nov 26. [20005104 ]
General Function:
Chloride peroxidase activity
Gene Name:
cpo
Uniprot ID:
O31158
Molecular Weight:
29651.125 Da
General Function:
Hydrolase activity
Gene Name:
cumD
Uniprot ID:
P96965
Molecular Weight:
31489.385 Da
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the interconversion of L-alanine and D-alanine. Also weakly active on serine.
Gene Name:
alr
Uniprot ID:
P10724
Molecular Weight:
43592.715 Da

From T3DB