Homocysteine-Thiolactone and S-Nitroso-Homocysteine Mediate Incorporation of Homocysteine into Protein in Humans (original) (raw)

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 e-amino group of protein lysine residues. _SNitroso_-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.

Published Online: 2005-06-01

Published in Print: 2003-11-17