Biochemical characterization of various catalytic complexes of the brain platelet-activating factor acetylhydrolase

Hiroshi Manya, Junken Aoki, Hiromi Kato, Junko Ishii, Shinji Hino, Hiroyuki Arai, Keizo Inoue

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52 Citations (Scopus)

Abstract

Brain intracellular platelet-activating factor acetylhydrolase (PAF-AH) isoform I is a member of a family of complex enzymes composed of mutually homologous α1 and α2 subunits, both of which account for catalytic activity, and the β subunit. We previously demonstrated that the expression of one catalytic subunit, α1, is developmentally regulated, resulting in a switching of the catalytic complex from α12 to α22 during brain development (Manya, H., Aoki, J., Watanabe, M., Adachi, T., Asou, H., Inoue, Y., Arai, H., and Inoue, K. (1998) J. Biol. Chem. 273, 18567-18572). In this study, we explored the biochemical differences in three possible catalytic dimers, α11, α12, and α22. The α22 homodimer exhibited different substrate specificity from the α11 homodimer and the α12 heterodimer, both of which showed similar substrate specificity. The α22 homodimer hydrolyzed PAF and 1-O-alkyl-2-acetyl- sn-glycero-3-phosphorylethanolamine (AAGPE) most efficiently among 1-O-alkyl- 2-acetyl-phospholipids. In contrast, both α11 and α22 hydrolyzed 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid more efficiently than PAF. AAGPE was the poorest substrate for these enzymes. The β subunit bound to all three catalytic dimers but modulated the enzyme activity in a catalytic dimer composition-dependent manner. The β subunit strongly accelerated the enzyme activity of the α22 homodimer but rather suppressed the activity of the α11 homodimer and had little effect on that of the α12 heterodimer. The (His149 to Arg) mutant β, which has been recently identified in isolated lissencephaly sequence patients, lost the ability to either associate with the catalytic complexes or modulate their enzyme activity. The enzyme activity of PAF-AH isoform I may be regulated in multiple ways by switching the composition of the catalytic subunit and by manipulating the subunit.

Original languageEnglish
Pages (from-to)31827-31832
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number45
DOIs
Publication statusPublished - 1999 Nov 5

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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