2. Academic Validation
  3. Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7

Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7

  • Biochim Biophys Acta. 2016 Dec;1861(12 Pt A):1881-1892. doi: 10.1016/j.bbalip.2016.09.008.
Iffat Ara Sonia Rahman 1,  Kazuhito Tsuboi 1,  Zahir Hussain 1,  Ryouhei Yamashita 2,  Yoko Okamoto 2,  Toru Uyama 1,  Naoshi Yamazaki 2,  Tamotsu Tanaka 2,  Akira Tokumura 3,  Natsuo Ueda 4
Affiliations

Affiliations

  • 1 Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
  • 2 Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, Japan.
  • 3 Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8505, Japan; Department of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, Hiroshima 731-0153, Japan.
  • 4 Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. Electronic address: [email protected].
PMID: 27637550 DOI: 10.1016/j.bbalip.2016.09.008
Abstract

N-Acylethanolamines form a class of lipid mediators and include an endocannabinoid arachidonoylethanolamide (anandamide), analgesic and anti-inflammatory palmitoylethanolamide, and appetite-suppressing oleoylethanolamide. In animal tissues, N-acylethanolamines are synthesized from N-acylated ethanolamine Phospholipids directly by N-acylphosphatidylethanolamine-hydrolyzing Phospholipase D or through multi-step pathways via N-acylethanolamine lysophospholipids. We previously reported that glycerophosphodiesterase (GDE) 4, a member of the GDE family, has lysophospholipase D (lysoPLD) activity hydrolyzing N-acylethanolamine lysophospholipids to N-acylethanolamines. Recently, GDE7 was shown to have lysoPLD activity toward lysophosphatidylcholine to produce lysophosphatidic acid (LPA). Here, we examined the reactivity of GDE7 with N-acylethanolamine lysophospholipids as well as the requirement of divalent cations for its catalytic activity. When overexpressed in HEK293 cells, recombinant GDE7 proteins of human and mouse showed lysoPLD activity toward N-palmitoyl, N-oleoyl, and N-arachidonoyl-lysophosphatidylethanolamines and N-palmitoyl-lysoplasmenylethanolamine to generate their corresponding N-acylethanolamines and LPAs. However, GDE7 hardly hydrolyzed glycerophospho-N-palmitoylethanolamine. Overexpression of GDE7 in HEK293 cells increased endogenous levels of N-acylethanolamines and LPAs. Interestingly, GDE7 was stimulated by micromolar concentrations of Ca2+ but not by millimolar concentrations of Mg2+, while GDE4 was stimulated by Mg2+ but was insensitive to Ca2+. GDE7 was widely distributed in various tissues of humans and mice with the highest levels in their kidney tissues. These results suggested that GDE7 is a novel Ca2+-dependent lysoPLD, which is involved in the generation of both N-acylethanolamines and LPAs.

Keywords

Glycerophosphodiesterase; Lysophosphatidic acid; Lysophospholipase D; N-acylethanolamine; Phospholipid.

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