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Homocysteine thiolactone

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Homocysteine thiolactone
Names
IUPAC name (3S)-3-aminothiolan-2-one
Identifiers
CAS Number
3D model (JSmol)
Beilstein Reference 80591
ChEBI
ChEMBL
ChemSpider
PubChem CID
InChI
  • InChI=1S/C4H7NOS/c5-3-1-2-7-4(3)6/h3H,1-2,5H2/t3-/m0/s1Key: KIWQWJKWBHZMDT-VKHMYHEASA-N
SMILES
  • C1CSC(=O)1N
Properties
Chemical formula C4H7NOS
Molar mass 117.17 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

Homocysteine thiolactone (HTL) is an organosulfur compound with the formula H2NCHC(O)SCH2CH2. It is the thiolactone (intramolecular thioester) of homocysteine. It is produced by methionyl-tRNA synthetase in an error-editing reaction that prevents translational incorporation of homocysteine into proteins.

HTL can damage proteins through "homocysteinylation" of protein lysine residues. HTL has been reported to form isopeptide bonds with lysine residues in substrate proteins, a post-translational modification known as N-homocysteinylation (N-hcy). This causes protein damage via a thiyl radical mechanism. The drugs citiolone and erdosteine are modified versions of homocysteine thiolactone.

When N-hcy binds α-syn, it exacerbates α-syn aggregation, neurotoxicity, and dopaminergic neuronal degeneration. It also damages the protein DJ-1, contributing to Parkinson's disease.

References

  1. Jakubowski, Hieronim (February 2000). "Homocysteine Thiolactone: Metabolic Origin and Protein Homocysteinylation in Humans". The Journal of Nutrition. 130 (2): 377S–381S. doi:10.1093/jn/130.2.377S. PMID 10721911.
  2. Perła-Kaján, J.; Twardowski, T.; Jakubowski, H. (2007). "Mechanisms of homocysteine toxicity in humans". Amino Acids. 32 (4): 561–572. doi:10.1007/s00726-006-0432-9. PMID 17285228.
  3. Guo, Tao; Zhou, Lingyan; Xiong, Min; Xiong, Jing; Huang, Juan; Li, Yiming; Zhang, Guoxin; Chen, Guiqin; Wang, Zhi-Hao; Xiao, Tingting; Hu, Dan; Bao, Anyu; Zhang, Zhentao (May 2024). "N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease". Aging Cell. 23 (5): e14124. doi:10.1111/acel.14124. PMC 11113254. PMID 38380563.
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