Chemistry:Homocysteine thiolactone
| |
| Names | |
|---|---|
| IUPAC name
(3S)-3-aminothiolan-2-one
| |
| Identifiers | |
3D model (JSmol)
|
|
| 80591 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
PubChem CID
|
|
| |
| |
| 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). | |
| Infobox references | |
Homocysteine thiolactone (HTL) is an organosulfur compound with the formula H
2NCHC(O)SCH
2CH
2. 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
- ↑ 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.
- ↑ 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.
- ↑ Guo, Tao; Zhou, Lingyan; Xiong, Min; Xiong, Jing; Huang, Juan; Li, Yiming; Zhang, Guoxin; Chen, Guiqin et al. (May 2024). "N-homocysteinylation of DJ-1 promotes neurodegeneration in Parkinson's disease". Aging Cell 23 (5). doi:10.1111/acel.14124. PMID 38380563.
 |  |
