Ramenskaia G V, Melnik E V, Petukhov A E
Sechenov First Moscow State Medical University (Sechenovskiy University), Moscow, Russia.
Sechenov First Moscow State Medical University (Sechenovskiy University), Moscow, Russia; Moscow Research and Practical Centre for Narcology, Moscow, Russia.
Biomed Khim. 2018 Jan;64(1):84-93. doi: 10.18097/PBMC20186401084.
Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.
磷脂酶D（PLD）是催化细胞膜磷脂水解的关键酶之一。本综述总结了目前关于六种人类PLD亚型的知识、它们的结构以及在生理和病理过程中的作用。文中呈现了PLD亚型结构的比较分析。描述了PLD进行水解和转磷脂酰化的机制。分析了PLD1和PLD2在某些癌症、感染性、血栓性和神经退行性疾病发病机制中的作用。在临床应用背景下展示了PLD亚型选择性抑制剂开发的前景，并对已有的抑制剂进行了特性描述。此外，还探讨了作为酒精滥用生物标志物的磷脂酰乙醇（PEth）通过PLD催化的磷脂转磷脂酰化反应形成的过程。
