Identification and origin of Nε-homocysteinyl-lysine isopeptide in humans and mice

Rafał Głowacki, Edward Bald, Hieronim Jakubowski

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Homocysteine (Hcy) metabolites, Hcy-thiolactone and N-Hcy-proteins, have been linked to the pathology of human cardiovascular and neurodegenerative diseases. Hcy-thiolactone is generated in an error-editing reaction in protein biosynthesis when Hcy is selected in place of methionine by methionyl-tRNA synthetase. N-Hcy-protein, in which Hcy is linked via isopeptide bond to ε-amino group of a protein lysine residue, forms in a post-translational reaction of Hcy-thiolactone with proteins. Here, we identify a novel metabolite, Nε-Hcy-Lys, in human and mouse plasma, and show that this metabolite is elevated in genetic (cystathionine β-synthase deficiency in humans and mice, methylenetetrahydrofolate reductase deficiency in mice) or dietary (high Met diet in mice) deficiencies in Hcy metabolism. We also show that Nε-Hcy-Lys is generated by proteolytic degradation of N-Hcy-protein in mouse liver extracts. Our data indicate that free Nε-Hcy-Lys is an important pathology-related component of Hcy metabolism in humans and mice.

Original languageEnglish (US)
Pages (from-to)1563-1569
Number of pages7
JournalAmino Acids
Volume39
Issue number5
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Keywords

  • Cystathionine β-synthase deficiency
  • Dietary hyperhomocysteinemia
  • Methylenetetrahydrofolate reductase deficiency
  • N-Hcy-protein turnover
  • Nε-Homocysteinyl-lysine

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