Propionic acid (T3D4444)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2014-08-29 06:51:18 UTC
Update Date2018-03-21 17:46:16 UTC
Accession NumberT3D4444
Identification
Common NamePropionic acid
ClassSmall Molecule
DescriptionPropionic 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).
Compound Type
  • Animal Toxin
  • Food Toxin
  • Household Toxin
  • Mammal Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Adofeed
Antischim B
Carboxyethane
Ethanecarboxylate
Ethanecarboxylic acid
Ethylformate
Ethylformic acid
Luprosil
Metacetonate
Metacetonic acid
Methylacetate
Methylacetic acid
MonoProp
Propanate
Propanoate
Propanoic acid
Propcorn
Propionate
Propkorn
Prozoin
Pseudoacetate
Pseudoacetic acid
Toxi-Check
Chemical FormulaC3H6O2
Average Molecular Mass74.079 g/mol
Monoisotopic Mass74.037 g/mol
CAS Registry Number79-09-4
IUPAC Namepropanoic acid
Traditional Namepropanoic acid
SMILESCCC(O)=O
InChI IdentifierInChI=1S/C3H6O2/c1-2-3(4)5/h2H2,1H3,(H,4,5)
InChI KeyInChIKey=XBDQKXXYIPTUBI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as carboxylic acids. Carboxylic acids are compounds containing a carboxylic acid group with the formula -C(=O)OH.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassCarboxylic acids
Direct ParentCarboxylic acids
Alternative Parents
Substituents
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Brain
  • Epidermis
  • Fibroblasts
  • Intestine
  • Muscle
  • Neuron
  • Platelet
  • Stratum Corneum
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Propanoate MetabolismSMP00016 map00640
Propionic AcidemiaSMP00236 Not Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point-20.7°C
Boiling Point140.99°C (285.8°F)
Solubility1000.0 mg/mL
LogP0.33
Predicted Properties
PropertyValueSource
Water Solubility352 g/LALOGPS
logP0.31ALOGPS
logP0.48ChemAxon
logS0.68ALOGPS
pKa (Strongest Acidic)4.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity17.27 m³·mol⁻¹ChemAxon
Polarizability7.24 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9000000000-51f674be972a6c17185b2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9000000000-691dcd080b30c98983502017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9000000000-51f674be972a6c17185b2018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004i-9000000000-691dcd080b30c98983502018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00b9-9000000000-abf322c73e6badb078bf2016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00fr-9100000000-cbfe9e32208652e700472017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-9000000000-1af60fc458a7f351a9b02012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-004i-9000000000-aa6e765fc867ac8be6412012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0006-9000000000-27e0b790e192d13044492012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-6M) , Positivesplash10-004i-9000000000-51f674be972a6c17185b2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80B) , Positivesplash10-004i-9000000000-90d9e0181596093a2f852012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-00di-9000000000-bdd7baa3d1bda886fb772012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-00di-9000000000-e73379c8765802cf32282012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-00di-9000000000-d6832c04c8b2ca0fdfa32012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-00di-9000000000-d0c93844dbfaed791bb02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-bdd7baa3d1bda886fb772017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-e73379c8765802cf32282017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-d6832c04c8b2ca0fdfa32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-00di-9000000000-d0c93844dbfaed791bb02017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-47364fadf00a5a2b7e932015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-9000000000-76fad523c005a65102642015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-9000000000-a1c0234da57ff32c6e122015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-47364fadf00a5a2b7e932015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-9000000000-76fad523c005a65102642015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-9000000000-a1c0234da57ff32c6e122015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-9000000000-db59da781a70634d25262015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05fr-9000000000-bea4ff21e6ab6c6644122015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-782832f8f5ab85f2ef4f2015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-9000000000-db59da781a70634d25262015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05fr-9000000000-bea4ff21e6ab6c6644122015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-782832f8f5ab85f2ef4f2015-05-27View Spectrum
MSMass Spectrum (Electron Ionization)splash10-00b9-9000000000-0bb3297c4159bed2316e2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
1D NMR1H NMR Spectrum (1D, D2O, experimental)Not Available2016-10-22View Spectrum
1D NMR13C NMR Spectrum (1D, D2O, experimental)Not Available2016-10-22View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 1H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureNot Available
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 (22, 23). (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 ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesThis is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
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)
SymptomsPropionic 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)
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)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB03766
HMDB IDHMDB00237
PubChem Compound ID1032
ChEMBL IDCHEMBL14021
ChemSpider ID1005
KEGG IDC00163
UniProt IDNot Available
OMIM ID
ChEBI ID30768
BioCyc IDPROPIONATE
CTD IDNot Available
Stitch IDNot Available
PDB IDPPI
ACToR IDNot Available
Wikipedia LinkPropionic acid
References
Synthesis Reference

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

MSDSLink
General References
  1. Harrison PT: Propionic acid and the phenomenon of rodent forestomach tumorigenesis: a review. Food Chem Toxicol. 1992 Apr;30(4):333-40. [1628870 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Lin SC, Bergles DE: Synaptic signaling between neurons and glia. Glia. 2004 Aug 15;47(3):290-8. [15252819 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  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 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Gephyrin
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [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. [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. [10592235 ]
Target Details
2. Free fatty acid receptor 2
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50130 uMNot AvailableBindingDB 50082199
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 ]