Paraoxonase 1 and homocysteine metabolism

Joanna Perła-Kaján, Hieronim Jakubowski

Research output: Contribution to journalReview articlepeer-review

87 Scopus citations

Abstract

Paraoxonase 1 (PON1), Acomponent of high-density lipoprotein (HDL), is Acalcium-dependent multifunctional enzyme that connects metabolisms of lipoproteins and homocysteine (Hcy). Both PON1 and Hcy have been implicated in human diseases, including atherosclerosis and neurodegeneration. The involvement of Hcy in disease could be mediated through its interactions with PON1. Due to its ability to reduce oxidative stress, PON1 contributes to atheroprotective functions of HDL in mice and humans. Although PON1 has the ability to hydrolyze Avariety of substrates, only one of themHcy-thiolactoneis known to occur naturally. In humans and mice, Hcy-thiolactonase activity of PON1 protects against N-homocysteinylation, which is detrimental to protein structure and function. PON1 also protects against neurotoxicity associated with hyperhomocysteinemia in mouse models. The links between PON1 and Hcy in relation to pathological states such as coronary artery disease, stroke, diabetic mellitus, kidney failure and Alzheimer's disease that emerge from recent studies are the topics of this review.

Original languageEnglish (US)
Pages (from-to)1405-1417
Number of pages13
JournalAmino Acids
Volume43
Issue number4
DOIs
StatePublished - Oct 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Keywords

  • Alzheimer's disease
  • Atherosclerosis
  • Homocysteine
  • N-homocysteinylation
  • Paraoxonase 1
  • Thiolactonase

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