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Platelet-activating factor acetylhydrolases: An overview and update.

Nozomu Kono1, Hiroyuki Arai2

  • 1Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; PRIME, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyodaku, Tokyo 100-0004, Japan.

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
|July 29, 2018
PubMed
Summary

Platelet-activating factor acetylhydrolases (PAF-AHs) are enzymes that break down PAF. Different PAF-AH types have distinct structures and functions, impacting diseases from cardiovascular conditions to allergies.

Keywords:
Oxidized phospholipidsPAF-AHPlatelet-activating factor

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Area of Science:

  • Biochemistry
  • Enzymology
  • Molecular Biology

Background:

  • Platelet-activating factor acetylhydrolases (PAF-AHs) are phospholipase A2 enzymes.
  • They hydrolyze the signaling phospholipid PAF, involved in various physiological and pathological processes.
  • Three mammalian PAF-AH types exist: plasma, intracellular PAF-AH (I), and intracellular PAF-AH (II).

Purpose of the Study:

  • To review the distinct characteristics and roles of mammalian PAF-AH enzymes.
  • To highlight the involvement of different PAF-AH types in various diseases and biological functions.
  • To discuss potential therapeutic implications, particularly for PAF-AH (II) in allergic diseases.

Main Methods:

  • Comparative analysis of structural and functional properties of PAF-AH isoforms.
  • Review of existing literature on the physiological and pathological roles of PAF-AHs.
  • Discussion of enzymatic activity towards PAF and other phospholipids.

Main Results:

  • Plasma PAF-AH and PAF-AH (II) are similar monomeric enzymes, while PAF-AH (I) is a distinct multimeric enzyme.
  • Plasma PAF-AH and PAF-AH (II) hydrolyze oxidized phospholipids, unlike PAF-AH (I).
  • PAF-AH (I) is crucial for spermatogenesis and implicated in cancer; PAF-AH (II) is involved in mast cell lipid production.

Conclusions:

  • Mammalian PAF-AHs exhibit diverse structures and substrate specificities.
  • Plasma PAF-AH is linked to cardiovascular disease, PAF-AH (I) to reproduction and cancer, and PAF-AH (II) to allergic responses.
  • PAF-AH (II) presents a potential drug target for treating allergic diseases.