Center for Human Nutrition, Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, Euclid Avenue, Campus Box 8031, St. Louis, MO 63110, USA.
Biomolecules. 2020 Sep 29;10(10):1386. doi: 10.3390/biom10101386.
Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound effects on signaling in a variety of cell types. Indeed, in most tissues except adipose tissue, lipin-mediated PA phosphohydrolase activity is far from limiting for normal rates of triglyceride synthesis, but rather impacts critical signaling cascades that control cellular homeostasis. In this review, we will discuss how lipin-mediated control of PA concentrations regulates metabolism and signaling in mammalian organisms.
磷酸脂酸（PA）是甘油三酯合成途径中的一种甘油磷脂中间产物，具有作为细胞膜组成部分的令人难以置信的重要结构功能，以及对细胞内和细胞间信号通路的动态影响。尽管有许多途径可以合成和降解 PA，但 PA 磷酸水解酶（lipin 家族蛋白）家族生成二酰基甘油，构成了将 PA 掺入甘油三酯的主要途径。以前，人们认为用于合成甘油三酯的 PA 池是独特的、分隔的，并且与信号通路没有广泛的交叉。然而，我们现在知道，调节 lipin 1 的活性对各种细胞类型的信号转导有深远的影响。事实上，除脂肪组织外，在大多数组织中，lipin 介导的 PA 磷酸水解酶活性对于正常的甘油三酯合成速率来说远非有限，但会影响控制细胞内稳态的关键信号级联反应。在这篇综述中，我们将讨论 lipin 介导的 PA 浓度控制如何调节哺乳动物生物体内的代谢和信号转导。
