Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid after phosphatidylcholine, comprising approximately 20–30% of total membrane phospholipids. It is defined by a diacylglycerol backbone esterified at the sn-3 position to phosphoethanolamine (-PO4-CH2CH2NH3+), which imparts a small, neutral zwitterionic headgroup favoring non-lamellar phases.

Molecular Structure

PE consists of sn-glycerol-3-phosphate with a characteristic acyl chain distribution: the sn-1 position is typically occupied by saturated fatty acids (16:0 or 18:0), whereas the sn-2 position often contains polyunsaturated chains such as 18:2, 20:4, or 22:6 (DHA). Common examples include DOPE (18:1/18:1) and soy-derived PE mixtures.

Structural variants include plasmenyl-PE, containing a sn-1 vinyl ether linkage that provides peroxide resistance in brain membranes, as well as lyso-PE species. Headgroup hydrogen bonding via NH3+ donors facilitates intermembrane interactions, while acyl remodeling through the Lands cycle modulates membrane curvature.

Biophysical Properties

In contrast to phosphatidylcholine (PC), whose bulky choline headgroup stabilizes bilayers, PE exhibits a conical geometry (V/aLc ~0.6–0.8) that promotes the formation of hexagonal HII phases. These phases are critical for membrane fusion processes and protein crowding, with PE predominantly localized in the inner leaflet of eukaryotic plasma membranes and within mitochondrial inner membranes.

PE generally displays a lower melting temperature (Tm) compared to PC homologs. For example, DOPE has a transition temperature near −16°C, while its hexagonal phase transition occurs around 10°C. Cholesterol has minimal influence on PE’s propensity for HII formation. Despite high hydration (~10 water molecules per lipid), PE remains strongly fusogenic and facilitates Ca²⁺-induced membrane fusion at contact sites below 1 nm.