Phospholipase D: Its Role in Metabolic Processes and Development of Diseases

Abstract

Phospholipase D (PLD; EC 3.1.4.4) is one of the key enzymes catalyzing hydrolysis of cell membrane phospholipids. This review considers and summaries current knowledge about six human PLD isoforms, their structure and a role in physiological and pathological processes. Comparative analysis of PLD isoforms structure is presented. The review considers the mechanism of hydrolysis and transphosphatidylation performed by PLD, the role of PLD1 and PLD2 in the pathogenesis of some types of cancer, infectious, thrombotic, and neurodegenerative diseases is analyzed. The prospects of development of PLD isoformselective inhibitors are considered in the context of their clinical use and inclusion into various therapeutic schemes; the latter is especially important in the case of already developed PLD inhibitors. Phosphatidylethanol (PEth) formed in the human body during phospholipid transphosphatidylation catalyzed by PLD is considered as an alcohol abuse biomarker.