Identification

Name
Propanoic acid
Accession Number
DB03766  (EXPT02641)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Sodium propionate is the sodium salt of propionic acid that exists as colorless, transparent crystals or a granular crystalline powder. It is considered generally recognized as safe (GRAS) food ingredient by FDA, where it acts as an antimicrobial agent for food preservation and flavoring agent. Its use as a food additive is also approved in Europe. Sodium propionate is is prepared by neutralizing propionic acid with sodium hydroxide. Sodium propionate was previously approved in Canada as an active ingredient in Amino-Cerv (used to treat inflammation or injury of the cervix).

Structure
Thumb
Synonyms
  • Propionic acid
External IDs
E-280 / FEMA NO. 2924 / INS NO.280 / INS-280
Product Ingredients
IngredientUNIICASInChI Key
Sodium propionateDK6Y9P42IN6700-17-0HOAUAOBUGFYWMK-UHFFFAOYSA-M
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Amino-cervSodium propionate (0.50 %) + Cystine (0.354 %) + Inositol (0.83 %) + Racemethionine (0.83 %) + Urea (8.34 %)CreamVaginalMilex, A Coopersurgical Co.1952-12-312007-07-26Canada
Categories
UNII
JHU490RVYR
CAS number
79-09-4
Weight
Average: 74.0785
Monoisotopic: 74.036779436
Chemical Formula
C3H6O2
InChI Key
XBDQKXXYIPTUBI-UHFFFAOYSA-N
InChI
InChI=1S/C3H6O2/c1-2-3(4)5/h2H2,1H3,(H,4,5)
IUPAC Name
propanoic acid
SMILES
CCC(O)=O

Pharmacology

Indication

Propanoic acid and various direct sodium or calcium salt formulations of the acid are currently most commonly approved and indicated by organizations like the FDA and EMA for use as an antibacterial food additive preservative in animal feed and food for human consumption [5, 6].

Similarly, although the use of propanoic acid or any of its direct sodium or calcium salt formulations as excipient ingredients in pharmaceuticals is not necessarily a major role for the compound today, sodium propionate was used in some vaginal cream preparations indicated for cervicitis, cervical tears, and/or postcauterization, postcryosurgery, and postconization of the cervix [3]. In such products, the sodium propionate was primarily used to elicit a preservative, bacteriostatic [4, 11] effect while other active ingredients combined in the formulation like urea, benzalkonium chloride, inositol, and methionine and cystine amino acids facilitated debridement, enhanced medication spread, epithelialization promotion, and wound healing, respectively [4, 1].

Nevertheless, a great variety of propionic acid derivatives exist as separate pharmaceuticals, each with their own unique therapeutic categories, pharmacodynamics, and pharmacokinetics.

Pharmacodynamics

As a naturally occurring carboxylic acid, propionic acid typically undergoes metabolism via conversion to propionyl coenzyme A (propionyl-CoA), which is part of the usual metabolic pathway that carboxylic acids participate within in the human body [2, 7]. Most of propionic acid's antibacterial and preservative activities subsequently stem from this metabolic pathway as the metabolic fate of propionates varies in different microorganisms, resulting in antimicrobial mechanisms of action that may revolve around differing propionate metabolites causing competition, inhibition, and/or interference effects along other metabolic pathways in the various microorganisms affected [7].

In the human body, however, propionic acid is generally metabolized with little ill effect and ultimately becomes a chemical intermediate in the citric acid cycle [7].

Mechanism of action

The metabolic fate of propionates varies in different microorganisms [7]. Some have enzyme systems that can convert succinate to propionyl-coenzyme A and through various further steps to propionate, CO2, or propionyl phoshpate [7]. Still others can convert propionic acid to B-alanine or directly to CO2 [7]. Whatever the case, the inhibiting effect for microbials is likely related to competition with acetate in the acetokinase system, to the blockage of pyruvate conversion to acetyl-coenzyme A and to interference with B-alanine in pantothenic acid syntheses [7].

Moreover, other studies suggest the antimicrobial activity of propionic acid revolves around its ability to reduce the pH of its immediate environment to levels of acidity that are harmful to pathogenic microbes as well as its ability to dissociate such that its lipid soluble undissociated form is capable of entering microbial cells [8]. Additionally, there are also studies that suggest that propionic acid's antifungal activity may be the result of propionyl-CoA inhibiting glucose metabolism in certain species of fungus via the accumulation of the CoA-derivative [2].

TargetActionsOrganism
UNon-heme chloroperoxidaseNot AvailablePseudomonas fluorescens
UGephyrinNot AvailableHuman
U2-hydroxy-6-oxo-7-methylocta-2,4-dienoate hydrolaseNot AvailablePseudomonas fluorescens
UAlanine racemaseNot AvailableGeobacillus stearothermophilus
Absorption

Some propionic acid is oxidized to lactic acid during absorption, but most passes to the liver, which removes nearly all of it from the portal blood [9]. Propionic acid represents 20-25% of absorbed volatile fatty acids [9].

Propionic acid is rapidly absorbed through the gastrointestinal tract [9].

Volume of distribution

Three days after a single oral administration of labeled sodium propionate, 77% of the radioactivity was found in expired air, and 7% in urine and feces [9]. The radioactivity found in skin, liver, intestine, and adipose tissue was 3.9, 1.1, 0.9, and 0.7%, respectively [9].

Readily accessible data regarding the volume of distribution of propionic acid is not available.

Protein binding

Readily accessible data regarding the protein binding of propionic acid is not available.

Metabolism

The metabolism of propionic acid starts with its transformation to propionyl coenzyme A (propionyl-CoA), the usual first step in the metabolism of carboxylic acids [7]. As propionic acid has three carbons, propionyl-CoA cannot directly enter either beta oxidation or the citric acid cycles [7]. In the majority of vertebrates, propionyl-CoA is carboxylated to D-methylmalonyl-CoA, which is then isomerised to L-methylmalonyl-CoA [7]. 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 [7].

Route of elimination

Most absorbed propionic acid is passed to the liver, which removes nearly all of it from the portal blood [9].

Three days after a single oral administration of labeled sodium propionate, 77% of the radioactivity was found in expired air, and 7% in urine and feces [9].

Half life

The half-life of iv sodium propionate administered in the sheep animal model is about 6.9 +/- 0.4 minutes [9].

Clearance

Readily accessible data regarding the clearance of propionic acid is not available.

Toxicity

As a compound that is typically found naturally in the body, little to no adverse cumulative health effects have been associated with exposure to propionic acid [10]. Medical reports of acute exposures of workers to propionic acid show mild to moderate skin burns, mild eye redness, and one case of a mild cough and asthmatic response [10].

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Propanoate MetabolismMetabolic
Malonic AciduriaDisease
Vitamin K MetabolismMetabolic
Conversion of Succinate to PropanoateMetabolic
Methylmalonic Aciduria Due to Cobalamin-Related DisordersDisease
Propanoate MetabolismMetabolic
Malonyl-CoA Decarboxylase DeficiencyDisease
Propanoyl-CoA DegradationMetabolic
Inner Membrane TransportMetabolic
Propanoate MetabolismMetabolic
Vitamin K MetabolismMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

James R. Hazen, "Process for production of 3-(hydroxyphenylphosphinyl)-propanoic acid." U.S. Patent US4769182, issued March, 1978.

US4769182
General References
  1. Ilic L, Gowrishankar TR, Vaughan TE, Herndon TO, Weaver JC: Spatially constrained skin electroporation with sodium thiosulfate and urea creates transdermal microconduits. J Control Release. 1999 Aug 27;61(1-2):185-202. [PubMed:10469915]
  2. Brock M, Buckel W: On the mechanism of action of the antifungal agent propionate. Eur J Biochem. 2004 Aug;271(15):3227-41. doi: 10.1111/j.1432-1033.2004.04255.x. [PubMed:15265042]
  3. Leonard G. Gomella, Steven A. Haist, Steven Haist (2003). Clinician's Pocket Drug Reference 2004 (3rd ed.). McGraw-Hill/Appleton & Lange. [ISBN:978-0071429450]
  4. RXmed.com: AMINO-CERV Monograph [Link]
  5. FDA Listing of Propionic Acid [Link]
  6. EFSA Journal: Safety of the extension of use of sodium propionate (E 281) as a food additive [Link]
  7. INCHEM Propionic Acid and its Calcium, Potassium, and Sodium Salts (WHO Food Additive Series 5) [Link]
  8. PROPIONIC ACID IS AN ALTERNATIVE TO ANTIBIOTICS IN POULTRY DIET [Link]
  9. PubChem Propionic Acid Profile [Link]
  10. NIH Toxnet: Propionic Acid Profile [Link]
  11. Compendium of Pharmaceutical Excipients for Vaginal Formulations [File]
External Links
Human Metabolome Database
HMDB0000237
KEGG Drug
D02310
KEGG Compound
C00163
PubChem Compound
1032
PubChem Substance
46508742
BindingDB
50082199
ChEBI
30768
ChEMBL
CHEMBL14021
IUPHAR
1062
Guide to Pharmacology
GtP Drug Page
HET
PPI
Wikipedia
Propionic_acid
ATC Codes
S01AX10 — Sodium propionate
PDB Entries
1a8s / 1adl / 1lic / 1lie / 1seg / 1tu9 / 1uk6 / 1uux / 1uuy / 2hub
show 28 more
MSDS
Download (62.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamVaginal
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)-20.7 °CPhysProp
boiling point (°C)141.1 °CPhysProp
water solubility1E+006 mg/L (at 25 °C)US EPA (1981)
logP0.33HANSCH,C ET AL. (1995)
pKa4.88SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
PropertyValueSource
Water Solubility352.0 mg/mLALOGPS
logP0.31ALOGPS
logP0.48ChemAxon
logS0.68ALOGPS
pKa (Strongest Acidic)4.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity17.27 m3·mol-1ChemAxon
Polarizability7.24 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9893
Blood Brain Barrier+0.941
Caco-2 permeable+0.6324
P-glycoprotein substrateNon-substrate0.7959
P-glycoprotein inhibitor INon-inhibitor0.9671
P-glycoprotein inhibitor IINon-inhibitor0.9909
Renal organic cation transporterNon-inhibitor0.9624
CYP450 2C9 substrateNon-substrate0.788
CYP450 2D6 substrateNon-substrate0.9394
CYP450 3A4 substrateNon-substrate0.8006
CYP450 1A2 substrateNon-inhibitor0.8922
CYP450 2C9 inhibitorNon-inhibitor0.9639
CYP450 2D6 inhibitorNon-inhibitor0.9667
CYP450 2C19 inhibitorNon-inhibitor0.9794
CYP450 3A4 inhibitorNon-inhibitor0.9763
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9876
Ames testNon AMES toxic0.9401
CarcinogenicityCarcinogens 0.6548
BiodegradationReady biodegradable0.9079
Rat acute toxicity1.4864 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9681
hERG inhibition (predictor II)Non-inhibitor0.9778
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-004i-9000000000-51f674be972a6c17185b
GC-MS Spectrum - EI-BGC-MSsplash10-004i-9000000000-691dcd080b30c9898350
Mass Spectrum (Electron Ionization)MSsplash10-00b9-9000000000-0bb3297c4159bed2316e
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)LC-MS/MSsplash10-004i-9000000000-1af60fc458a7f351a9b0
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)LC-MS/MSsplash10-004i-9000000000-aa6e765fc867ac8be641
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-0006-9000000000-27e0b790e192d1304449
MS/MS Spectrum - EI-B (HITACHI RMU-6M) , PositiveLC-MS/MSsplash10-004i-9000000000-51f674be972a6c17185b
MS/MS Spectrum - EI-B (HITACHI M-80B) , PositiveLC-MS/MSsplash10-004i-9000000000-90d9e0181596093a2f85
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, NegativeLC-MS/MSsplash10-00di-9000000000-bdd7baa3d1bda886fb77
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, NegativeLC-MS/MSsplash10-00di-9000000000-e73379c8765802cf3228
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, NegativeLC-MS/MSsplash10-00di-9000000000-d6832c04c8b2ca0fdfa3
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, NegativeLC-MS/MSsplash10-00di-9000000000-d0c93844dbfaed791bb0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-47364fadf00a5a2b7e93
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-9000000000-76fad523c005a6510264
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-9000000000-a1c0234da57ff32c6e12
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-47364fadf00a5a2b7e93
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-9000000000-76fad523c005a6510264
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-9000000000-a1c0234da57ff32c6e12
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9000000000-db59da781a70634d2526
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fr-9000000000-bea4ff21e6ab6c664412
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-782832f8f5ab85f2ef4f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9000000000-db59da781a70634d2526
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fr-9000000000-bea4ff21e6ab6c664412
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-782832f8f5ab85f2ef4f
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00di-9000000000-bdd7baa3d1bda886fb77
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00di-9000000000-e73379c8765802cf3228
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00di-9000000000-d6832c04c8b2ca0fdfa3
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00di-9000000000-d0c93844dbfaed791bb0
13C NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
[1H,1H] 2D NMR Spectrum2D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Carboxylic acids
Direct Parent
Carboxylic acids
Alternative Parents
Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Monocarboxylic acid or derivatives / Carboxylic acid / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Carbonyl group / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
saturated fatty acid, short-chain fatty acid (CHEBI:30768) / Straight chain fatty acids, Saturated fatty acids (C00163) / Straight chain fatty acids (LMFA01010003)

Targets

Kind
Protein
Organism
Pseudomonas fluorescens
Pharmacological action
Unknown
General Function
Chloride peroxidase activity
Specific Function
Not Available
Gene Name
cpo
Uniprot ID
O31158
Uniprot Name
Non-heme chloroperoxidase
Molecular Weight
29651.125 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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). Ca...
Gene Name
GPHN
Uniprot ID
Q9NQX3
Uniprot Name
Gephyrin
Molecular Weight
79747.635 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. 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. [PubMed:10592235]
Kind
Protein
Organism
Pseudomonas fluorescens
Pharmacological action
Unknown
General Function
Hydrolase activity
Specific Function
Not Available
Gene Name
cumD
Uniprot ID
P96965
Uniprot Name
2-hydroxy-6-oxo-7-methylocta-2,4-dienoate hydrolase
Molecular Weight
31489.385 Da
Kind
Protein
Organism
Geobacillus stearothermophilus
Pharmacological action
Unknown
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
Uniprot Name
Alanine racemase
Molecular Weight
43592.715 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transporter activity
Specific Function
Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus (By similarity).
Gene Name
FABP4
Uniprot ID
P15090
Uniprot Name
Fatty acid-binding protein, adipocyte
Molecular Weight
14718.815 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. 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. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 09:14