Homocysteine thiolactone

Homocysteine thiolactone

Names
IUPAC name (3S)-3-aminothiolan-2-one
Identifiers
CAS Number	2338-04-7
3D model (JSmol)	Interactive image
Beilstein Reference	80591
ChEBI	CHEBI:60315
ChEMBL	ChEMBL4078313
ChemSpider	118559
PubChem CID	134505
InChI InChI=1S/C4H7NOS/c5-3-1-2-7-4(3)6/h3H,1-2,5H2/t3-/m0/s1 Key: KIWQWJKWBHZMDT-VKHMYHEASA-N
SMILES C1CSC(=O)[C@H]1N
Properties
Chemical formula	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). Infobox references

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.