Regulation of Phosphatidylethanolamine Homeostasis — The Critical Role of CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)

Abstract

Phosphatidylethanolamine (PE) is the most abundant lipid on the protoplasmatic leaflet of cellular membranes. It has a pivotal role in cellular processes such as membrane fusion, cell cycle regulation, autophagy, and apoptosis. CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) is the main regulatory enzyme in de novo biosynthesis of PE from ethanolamine and diacylglycerol by the CDP-ethanolamine Kennedy pathway. The following is a summary of the current state of knowledge on Pcyt2 and how splicing and isoform specific differences could lead to variations in functional properties in this family of enzymes. Results from the most recent studies on Pcyt2 transcriptional regulation, promoter function, autophagy, and cell growth regulation are highlighted. Recent data obtained from Pcyt2 knockout mouse models is also presented, demonstrating the essentiality of this gene in embryonic development as well as the major physiological consequences of deletion of one Pcyt2 allele. Those include development of symptoms of the metabolic syndrome such as elevated lipogenesis and lipoprotein secretion, hypertriglyceridemia, liver steatosis, obesity, and insulin resistance. The objective of this review is to elucidate the nature of Pcyt2 regulation by linking its catalytic function with the regulation of lipid and energy homeostasis.

Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health

“…Pcyt2 encodes CPT: phosphoethanolamine cytidylyltransferase, the main regulatory enzyme in the de novo ethanolamine phospholipids synthesis (Pavlovic and Bakovic 2013). The meaning of underexpression of this gene in PBMCs at an early stage of life, as occurring in CR animals, remains to be determined.…”

Isoform-specific and Protein Kinase C-mediated Regulation of CTP:Phosphoethanolamine Cytidylyltransferase Phosphorylation

“…In the final step, CDPethanolamine:1,2-diacylglycerol ethanolamine phosphotransferase transfers P-Etn from CDP-Etn to DAG/alkylacylglycerol to produce PE/plasmalogens. We have recently reviewed the role of Pcyt2 in phospholipid homeostasis (10).…”

Dipalmitoleoylphosphoethanolamine as a PP2A Enhancer Obstructs Insulin Signaling by Promoting Ser/Thr Dephosphorylation of Akt

“…Three main biochemical pathways are recognized for production of phosphatidylethanolamine; CDP-ethanolamine Kennedy pathway, mitochondrial phosphatidylserine decarboxylation pathway catalyzed by phosphatidylserine decarboxylase, and acylation of lysophosphatidylethanolamine catalyzed by lysophosphatidylethanolamine acyltransferase. CDP-ethanolamine Kennedy pathway is the only route for de novo synthesis of phosphatidylethanolamine [22]. Phosphorylation of ethanolamine by ethanolamine kinase to produce phosphoethanolamine is followed by the CTP:choline cytidylyltransferase 2 (Pcyt2)-mediated production of CDP-ethanolamine.…”