Aoki Junken, Nagai Yuki, Hosono Hiroyuki, Inoue Keizo, Arai Hiroyuki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Biochim Biophys Acta. 2002 May 23;1582(1-3):26-32. doi: 10.1016/s1388-1981(02)00134-8.
Phospholipase A1 (PLA1) is an enzyme that hydrolyzes the sn-1 fatty acids from phospholipids and produces 2-acyl-lysophospholipids. Although PLA1 activities are detected in many tissues and cell lines, a limited number of PLA1s have been purified and cloned so far. These include phosphatidylserine (PS)-specific PLA1 (PS-PLA1) from rat platelets, PLA1 from vespid venom, and phosphatidic acid (PA)-preferential PLA1 (PA-PLA1). Structurally, the former two PLA1s belong to the lipase family, where they form a subfamily among the lipase family. An alignment of the PLA1s with other members of the lipase family revealed two molecular characteristics of PLA1: the presence of extremely short lids and deleted beta9 loops. The two surface loops have been implicated in the ligand recognition in human pancreatic lipase (PL) and guinea pig PL-related protein 2. Under physiological conditions, accessibility of PS-PLA1 to its substrate is limited as it is a secreted enzyme and PS is normally located in the inner leaflet of the lipid bilayer. However, PS-PLA1 efficiently hydrolyzes PS exposed on the surface of cells such as apoptotic cells and activated platelets, and produces 2-acyl-lysophosphatidylserine (lysoPS), which is a lipid mediator for mast cells, T cells and neural cells. Identification of PS-PLA1 reveals the presence of PLA1 subfamily within the lipase family and suggests that PLA1 has a role in the production of lysophospholipid mediators.
磷脂酶A1(PLA1)是一种能从磷脂中水解sn-1脂肪酸并生成2-酰基溶血磷脂的酶。尽管在许多组织和细胞系中都检测到了PLA1的活性,但到目前为止,仅有少数PLA1被纯化和克隆。这些包括来自大鼠血小板的磷脂酰丝氨酸(PS)特异性PLA1(PS-PLA1)、来自黄蜂毒液的PLA1以及磷脂酸(PA)优先PLA1(PA-PLA1)。在结构上,前两种PLA1属于脂肪酶家族,它们在脂肪酶家族中形成一个亚家族。将PLA1与脂肪酶家族的其他成员进行比对,揭示了PLA1的两个分子特征:存在极短的盖子和缺失的β9环。这两个表面环与人类胰腺脂肪酶(PL)和豚鼠PL相关蛋白2中的配体识别有关。在生理条件下,PS-PLA1对其底物的可及性有限,因为它是一种分泌酶,而PS通常位于脂质双层的内小叶。然而,PS-PLA1能有效水解暴露在细胞表面(如凋亡细胞和活化血小板)的PS,并生成2-酰基溶血磷脂酰丝氨酸(溶血PS),这是一种针对肥大细胞、T细胞和神经细胞的脂质介质。PS-PLA1的鉴定揭示了脂肪酶家族中PLA1亚家族的存在,并表明PLA1在溶血磷脂介质的产生中起作用。