Homocysteine thiolactone

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Homocysteine thiolactone
Homocysteine thiolactone.svg
Names
IUPAC name
(3S)-3-aminothiolan-2-one
Identifiers
3D model (JSmol)
80591
ChEBI
ChEMBL
ChemSpider
PubChem CID
  • InChI=1S/C4H7NOS/c5-3-1-2-7-4(3)6/h3H,1-2,5H2/t3-/m0/s1
    Key: KIWQWJKWBHZMDT-VKHMYHEASA-N
  • C1CSC(=O)[C@H]1N
Properties
C4H7NOS
Molar mass 117.17 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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. [1] 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. [2] 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. [3]

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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