The mechanism and consequences of homocysteine incorporation into protein in humans

Research output: Contribution to journalArticle

2 Citations (Scopus)

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
StatePublished - Apr 1 2013

Fingerprint

Homocysteine
Biosynthesis
Proteins
Methionine-tRNA Ligase
Protein Biosynthesis
Metabolites
Metabolism
Methionine
Lysine
Chemical reactions
Bacteria
Degradation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry
  • Inorganic Chemistry

Keywords

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

Cite this

@article{da9375f625754062aa66561096484c38,
title = "The mechanism and consequences of homocysteine incorporation into protein in humans",
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.",
keywords = "Homocysteine thiolactone, cardiovascular disease, genetic & nutritional hyperhomocysteinemia, neurodegenerative disease, protein modification",
author = "Hieronim Jakubowski",
year = "2013",
month = "4",
day = "1",
doi = "10.1080/10426507.2012.736104",
language = "English (US)",
volume = "188",
pages = "384--395",
journal = "Phosphorus, Sulfur and Silicon and the Related Elements",
issn = "1042-6507",
publisher = "Taylor and Francis Ltd.",
number = "4",

}

TY - JOUR

T1 - The mechanism and consequences of homocysteine incorporation into protein in humans

AU - Jakubowski, Hieronim

PY - 2013/4/1

Y1 - 2013/4/1

N2 - 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.

AB - 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.

KW - Homocysteine thiolactone

KW - cardiovascular disease

KW - genetic & nutritional hyperhomocysteinemia

KW - neurodegenerative disease

KW - protein modification

UR - http://www.scopus.com/inward/record.url?scp=84879083764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879083764&partnerID=8YFLogxK

U2 - 10.1080/10426507.2012.736104

DO - 10.1080/10426507.2012.736104

M3 - Article

AN - SCOPUS:84879083764

VL - 188

SP - 384

EP - 395

JO - Phosphorus, Sulfur and Silicon and the Related Elements

JF - Phosphorus, Sulfur and Silicon and the Related Elements

SN - 1042-6507

IS - 4

ER -