The mechanism and consequences of homocysteine incorporation into protein in humans

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Abstract

Protein-related homocysteine (Hcy) metabolism generates Hcy-thiolactone thioester (1), N-Hcy-protein adducts (2), and Nε-Hcy-Lys) isopeptide (3). (1) is generated in an enzymatic error-editing reaction in protein biosynthesis when Hcy is erroneously selected in place of methionine by methionyl-tRNA synthetase. The Hcy editing reaction and the biosynthesis of (1) are universally conserved from bacteria to humans. (2) is formed in a chemical reaction of (1) with ε-amino groups of protein lysine residues in mice and humans. (3) is a product of proteolytic degradation of (2) that occurs in mice and humans. Chemical biology and pathophysiology of these metabolites is summarized in this review.

Original languageEnglish (US)
Pages (from-to)384-395
Number of pages12
JournalPhosphorus, Sulfur and Silicon and the Related Elements
Volume188
Issue number4
DOIs
Publication statusPublished - Apr 1 2013

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry
  • Inorganic Chemistry

Keywords

  • Homocysteine thiolactone
  • cardiovascular disease
  • genetic & nutritional hyperhomocysteinemia
  • neurodegenerative disease
  • protein modification

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