title: Homocysteine-thiolactone and S-nitroso-homocysteine mediate incorporation of homocysteine into protein in humans.
abstract: Indirect pathways, involving homocysteine (Hcy)-thiolactone and S-nitroso-Hcy, allow incorporation of Hcy into protein. Hcy-thiolactone, synthesized by methionyl-tRNA synthetase in all organisms investigated, including human, modifies proteins post-translationally by forming adducts in which Hcy is linked by amide bonds to epsilon-amino group of protein lysine residues. S-Nitroso-Hcy, synthesized in human vascular endothelial cells, is incorporated translationally into peptide bonds in protein at positions normally occupied by methionine. Hcy-N-hemoglobin and Hcy-N-albumin constitute a major pool of Hcy in human blood. Hcy-thiolactone is present in human plasma. Modification with Hcy-thiolactone leads to protein damage. Hcy-thiolactone is detoxified by Hcy-thiolactonase/paraoxonase present in a subset of high-density lipoprotein particles in humans.
authors.affiliation: Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark 07101-1709, USA. jakubows@umdnj.edu
authors.forename: Hieronim
authors.initials: H
authors.lastname: Jakubowski
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins; D006710:Homocysteine; C079202:S-nitrosohomocysteine; C007957:homocysteine thiolactone