Structure and Biological Function of ENPP6, a Choline-specific Glycerophosphodiester-phosphodiesterase

Overview

Journal Sci Rep

Specialty Science

Date 2016 Feb 19

PMID 26888014

Citations 36

Authors

Junko Morita

Kuniyuki Kano

Kazuki Kato

Hiroyuki Takita

Hideki Sakagami

Yasuo Yamamoto

Emiko Mihara

Hirofumi Ueda

Takanao Sato

Hidetoshi Tokuyama

Hiroyuki Arai

Hiroaki Asou

Junichi Takagi

Ryuichiro Ishitani

Hiroshi Nishimasu

Osamu Nureki

Junken Aoki

Affiliations

Soon will be listed here.

Abstract

Choline is an essential nutrient for all living cells and is produced extracellularly by sequential degradation of phosphatidylcholine (PC). However, little is known about how choline is produced extracellularly. Here, we report that ENPP6, a choline-specific phosphodiesterase, hydrolyzes glycerophosphocholine (GPC), a degradation product of PC, as a physiological substrate and participates in choline metabolism. ENPP6 is highly expressed in liver sinusoidal endothelial cells and developing oligodendrocytes, which actively incorporate choline and synthesize PC. ENPP6-deficient mice exhibited fatty liver and hypomyelination, well known choline-deficient phenotypes. The choline moiety of GPC was incorporated into PC in an ENPP6-dependent manner both in vivo and in vitro. The crystal structure of ENPP6 in complex with phosphocholine revealed that the choline moiety of the phosphocholine is recognized by a choline-binding pocket formed by conserved aromatic and acidic residues. The present study provides the molecular basis for ENPP6-mediated choline metabolism at atomic, cellular and tissue levels.

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