Imidazol-4-one-5-propionic acid

Imidazol-4-one-5-propionic acid
Names
	IUPAC name 3-(5-Oxo-1,4-dihydroimidazol-4-yl)propanoic acid
Identifiers
CAS Number	17340-16-8 ;
3D model (JSmol)	Interactive image;
ChemSpider	125 ;
KEGG	C03680;
MeSH	Imidazol-4-one-5-propionic+acid
PubChem CID	128;
CompTox Dashboard (EPA)	DTXSID10864771 DTXSID40938378, DTXSID10864771 ;
	InChI InChI=1S/C6H8N2O3/c9-5(10)2-1-4-6(11)8-3-7-4/h3-4H,1-2H2,(H,9,10)(H,7,8,11) Key: HEXMLHKQVUFYME-UHFFFAOYSA-N ;
	SMILES O=C1N\C=N/C1CCC(=O)O;
Properties
Chemical formula	C6H8N2O3
Molar mass	156.139
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Imidazol-4-one-5-propionic acid is an intermediate in the metabolism of histidine. It is a colorless compound that is sensitive to light and air. The compound features an imidazolone ring.^[1]

Biosynthesis and metabolism

Imidazol-4-one-5-propionic acid is produced by the breakdown of the amino acid, histidine. Its immediate precursor is urocanic acid via the action of urocanase:^[1]

urocanic acid

H₂O

Rightward reaction arrow with minor substrate(s) from top left

imidazol-4-one-5-propionic acid

The sequence continues when imidazolonepropionase converts this by hydrolysis to give formiminoglutamic acid:

imidazol-4-one-5-propionic acid

H₂O

formiminoglutamic acid

This reaction gives selectively a single enantiomer of the product, which is a derivative of L-glutamic acid.^[2]^[3]

Clinical significance

Microbial production of imidazol-4-one-5-propionic acid in the human gut has been shown to affect insulin signaling, which is relevant to type II diabetes.^[4]

Imidazole propionate has been causally implicated in atherosclerosis and Parkinson’s disease, primarily by triggering inflammation. Streptococcus mutans, known for its role in dental caries, has been identified as a contributor to elevated ImP levels through the urdA gene, which is involved in the conversion of urocanate to ImP.^[5]^[6]

References

1 2 Hassall, H.; Greenberg, D. M. (1971). "The preparation and properties of 4(5)-imidazolone-5(4)-propionic acid". Metabolism of Amino Acids and Amines Part B. Methods Enzymol. Vol. 17(Pt. B). pp. 89–91. doi:10.1016/0076-6879(71)17014-0. ISBN 978-0-12-181877-7.
↑ Yu, Yamei; Liang, Yu-He; Brostromer, Erik; Quan, Jun-Min; Panjikar, Santosh; Dong, Yu-Hui; Su, Xiao-Dong (2006). "A Catalytic Mechanism Revealed by the Crystal Structures of the Imidazolonepropionase from Bacillus subtilis". Journal of Biological Chemistry. 281 (48): 36929–36936. doi:10.1074/jbc.M607703200. PMID 16990261.
↑ Su, Hao; Sheng, Xiang; Liu, Yongjun (2016). "Exploring the substrate specificity and catalytic mechanism of imidazolonepropionase (HutI) from Bacillus subtilis". Physical Chemistry Chemical Physics. 18 (40): 27928–27938. doi:10.1039/c6cp04918d. PMID 27711543.
↑ Koh, Ara; Molinaro, Antonio; Ståhlman, Marcus; Khan, Muhammad Tanweer; Schmidt, Caroline; Mannerås-Holm, Louise; Wu, Hao; Carreras, Alba; Jeong, Heeyoon; Olofsson, Louise E.; Bergh, Per-Olof; Gerdes, Victor; Hartstra, Annick; De Brauw, Maurits; Perkins, Rosie; Nieuwdorp, Max; Bergström, Göran; Bäckhed, Fredrik (2018). "Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1". Cell. 175 (4): 947–961.e17. doi:10.1016/j.cell.2018.09.055. PMID 30401435. S2CID 53229780.
↑ Park, H.; Cheon, J.; Kim, H.; et al. (2025). "Gut microbial production of imidazole propionate drives Parkinson's pathologies". Nature Communications. 16: 8216. doi:10.1038/s41467-025-63473-4. PMC 12413466.
↑ Mastrangelo, A.; Robles-Vera, I.; Mañanes, D.; et al. (2025). "Imidazole propionate is a driver and therapeutic target in atherosclerosis". Nature. 645: 254–261. doi:10.1038/s41586-025-09263-w. hdl:10261/419343.

[Hassall-1] 1 2 Hassall, H.; Greenberg, D. M. (1971). "The preparation and properties of 4(5)-imidazolone-5(4)-propionic acid". Metabolism of Amino Acids and Amines Part B. Methods Enzymol. Vol. 17(Pt. B). pp. 89–91. doi:10.1016/0076-6879(71)17014-0. ISBN 978-0-12-181877-7.

[2] Yu, Yamei; Liang, Yu-He; Brostromer, Erik; Quan, Jun-Min; Panjikar, Santosh; Dong, Yu-Hui; Su, Xiao-Dong (2006). "A Catalytic Mechanism Revealed by the Crystal Structures of the Imidazolonepropionase from Bacillus subtilis". Journal of Biological Chemistry. 281 (48): 36929–36936. doi:10.1074/jbc.M607703200. PMID 16990261.

[3] Su, Hao; Sheng, Xiang; Liu, Yongjun (2016). "Exploring the substrate specificity and catalytic mechanism of imidazolonepropionase (HutI) from Bacillus subtilis". Physical Chemistry Chemical Physics. 18 (40): 27928–27938. doi:10.1039/c6cp04918d. PMID 27711543.

[4] Koh, Ara; Molinaro, Antonio; Ståhlman, Marcus; Khan, Muhammad Tanweer; Schmidt, Caroline; Mannerås-Holm, Louise; Wu, Hao; Carreras, Alba; Jeong, Heeyoon; Olofsson, Louise E.; Bergh, Per-Olof; Gerdes, Victor; Hartstra, Annick; De Brauw, Maurits; Perkins, Rosie; Nieuwdorp, Max; Bergström, Göran; Bäckhed, Fredrik (2018). "Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1". Cell. 175 (4): 947–961.e17. doi:10.1016/j.cell.2018.09.055. PMID 30401435. S2CID 53229780.

[5] Park, H.; Cheon, J.; Kim, H.; et al. (2025). "Gut microbial production of imidazole propionate drives Parkinson's pathologies". Nature Communications. 16: 8216. doi:10.1038/s41467-025-63473-4. PMC 12413466.

[6] Mastrangelo, A.; Robles-Vera, I.; Mañanes, D.; et al. (2025). "Imidazole propionate is a driver and therapeutic target in atherosclerosis". Nature. 645: 254–261. doi:10.1038/s41586-025-09263-w. hdl:10261/419343.

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