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Review
. 2017;2017:4829180.
doi: 10.1155/2017/4829180. Epub 2017 Jul 12.

Ethanolamine and Phosphatidylethanolamine: Partners in Health and Disease

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Free PMC article
Review

Ethanolamine and Phosphatidylethanolamine: Partners in Health and Disease

Dhaval Patel et al. Oxid Med Cell Longev. .
Free PMC article

Abstract

Phosphatidylethanolamine (PE) is the second most abundant phospholipid in mammalian cells. PE comprises about 15-25% of the total lipid in mammalian cells; it is enriched in the inner leaflet of membranes, and it is especially abundant in the inner mitochondrial membrane. PE has quite remarkable activities: it is a lipid chaperone that assists in the folding of certain membrane proteins, it is required for the activity of several of the respiratory complexes, and it plays a key role in the initiation of autophagy. In this review, we focus on PE's roles in lipid-induced stress in the endoplasmic reticulum (ER), Parkinson's disease (PD), ferroptosis, and cancer.

Figures

Figure 1
Figure 1
Lipids with a phosphoethanolamine head group.
Figure 2
Figure 2
Synthesis of PE via the two major pathways in cells, the Kennedy pathway (ER) and the PSD reaction (mitochondria). The two parallel branches of the Kennedy pathway are the CDP-ethanolamine pathway and the CDP-choline pathway. The four precursors needed for these reactions are choline, ethanolamine, cytosine triphosphate (CTP), and diacylglycerol (DAG). PS is synthesized in the ER via two base-exchange reactions (PSS1 and PSS2). The enzyme PEMT methylates PE to PC. PE is decarboxylated in the inner mitochondrial membrane by PSD (Psd1). CDP: cytidyl diphosphate; CTP: cytidyltriphosphate; DAG: diacylglycerol.
Figure 3
Figure 3
A GPI-AP. A GPI-AP is composed of a lipid tail (green), a conserved glycan core (blue) with attached phosphoethanolamine groups (blue), and the modified protein (red). A phosphoethanolamine moiety, which is extracted from PE, serves as the chemical linker between the GPI anchor and the protein.
Figure 4
Figure 4
Model for the aggregation of the PD-associated protein α-synuclein. Low PE generates lipid-induced ER stress and disrupts the synthesis and vesicular trafficking of GPI-APs. The disruption of GPI-APs via low PE or mutations in a GPI anchor gene triggers α-synuclein to form cytoplasmic foci. Similar foci form when the synthesis of ergosterol/cholesterol or sphingolipids is inhibited pharmacologically or via mutation. Ergosterol/cholesterol and sphingolipids make up lipid rafts and GPI-APs partition into lipid rafts. Disrupting GPI-anchor protein synthesis or lipid raft composition results in the formation of α-synuclein foci. Modified from [86].
Figure 5
Figure 5
Ophiobolin A (OPA) and its cytotoxic adduct with PE (OPA-PE). PE is abundant in the inner leaflet of most cell membranes. However, by unknown mechanisms, some cancer cells flip PE from the inner leaflet to the outer leaflet. OPA has been proposed to react with the PE in the outer leaflet generating a cytotoxic species that causes leaky membranes and that eventually kills the cells.
Figure 6
Figure 6
PE in cancer and ferroptosis. Left panel: PE and PS transfer to the outer leaflet of the plasma membrane in some cancers. OPA reacts with surface-exposed PE to yield a cytotoxic adduct that creates leaky membranes (arrows) that kills cells. Right panel: Lipoxygenase (15-Lox) oxidizes PE in the membranes of the ER. The oxidation requires that PE contains polyunsaturated acyl chains like arachidonic acid (A) or adrenic acid (AdA). The end product is doubly and triply oxidized hydroxyperoxide PE species that mediate cell death.

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