PlumX Metrics
Embed PlumX Metrics

Protein N -homocysteinylation: implications for atherosclerosis

Biomedicine & Pharmacotherapy, ISSN: 0753-3322, Vol: 55, Issue: 8, Page: 443-447
2001
  • 72
    Citations
  • 0
    Usage
  • 26
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Elevated levels of homocysteine (Hcy) are associated with various human pathologies, including cardiovascular disease. However, it is not exactly known why Hcy is harmful. A plausible hypothesis is that the indirect incorporation of Hcy into protein, referred to as protein N -homocysteinylation, leads to cell damage. A translational pathway involves: 1) reversible S -nitrosylation of Hcy with nitric oxide produced by nitric oxide synthase; 2) aminoacylation of tRNA Met with S -nitroso-Hcy catalyzed by MetRS; and 3) transfer of S -nitroso-Hcy from S -nitroso-Hcy-tRNA Met into growing polypeptide chains at positions normally occupied by methionine. Subsequent trans-nitrosylation leaves Hcy in the protein chain. A post-translational pathway involves: 1) metabolic conversion of Hcy to thiolactone by methionyl-tRNA synthetase (MetRS), and 2) acylation of protein lysine residues by Hcy thiolactone. The levels of Hcy thiolactone and N -homocysteinylated protein in human vascular endothelial cells depend on the ratio of Hcy/Met, levels of folic acid, and HDL, factors linked to cardiovascular disease. HDL-associated human serum Hcy thiolactonase/paraoxonase hydrolyzes thiolactone to Hcy, thereby minimizing protein N -homocysteinylation. Variations in Hcy thiolactonase may play an important role in Hcy-associated human cardiovascular disease.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know