第二世代の生理活性脂質リゾリン脂質

Lysophospholipids as second-generation lipid mediators

脂質は生体膜の成分として重要なだけでなく，ある種の状況において膜脂質より産生され，生理活性脂質として機能する．このような脂質は“脂質メディエーター”として知られている．ステロイドホルモンやアラキドン酸代謝物であるエイコサノイドに代表されるような第1世代の脂質メディエーターに加え，近年，単なる脂質代謝中間代謝物としてしか考えられていなかったリゾリン脂質が，第2世代の脂質メディエーターとして注目を浴びている．ゲノムに直接コードされていない脂質メディエーターは，どのように産生され，どのような機能を果たすのだろうか．本稿では，代表的なリゾリン脂質であるリゾホスファチジン酸，スフィンゴシン-1-リン酸，リゾホスファチジルセリンの生理作用を，その産生酵素や受容体と絡めて，最新のトピックスとともに紹介する．

Lipids are important not only as components of cellular membranes but as bioactive mediators produced from membrane lipids in a particular condition.　Such lipids are known as "lipid mediators".　In addition to first-generation lipid mediators such as steroid hormones and eicosanoids, lysophospholipids, which had been viewed just as a metabolic intermediate in the de novo lipid synthetic pathway, have recently been paid much attention to as second-generation lipid mediators.　Because lipids aren't coded by the genome directly, it is difficult to know their patho- and physiological roles.　However, recent studies have identified several key factors mediating the biological roles of lysophospholipid mediators such as receptors and producing enzymes.　In addition, the studies of transgenic animals of these lysophospholipid-related proteins, have revealed the biological significance of lysophospholipid mediators.　In this review we will summarize the recent advance in the studies of lysophosphatidic acid (LPA), sphingosine-1-phosphate (S1P) and lysophosphatidylserine (LysoPS).