Phospholipids and Ether Lipids

Phospholipids

• Phosphatidalethanolamine is abundant in nerve tissue and is similar in structure to phosphatidylethanolamine.
• Phosphatidalcholine is abundant in heart muscle and is a quantitatively significant ether lipid in mammals.

Platelet-Activating Factor (PAF)

• PAF is an ether glycerophospholipid with a saturated alkyl group in an ether link to carbon 1 and an acetyl residue at carbon 2 of the glycerol backbone.
• PAF is synthesized and released by various cell types, binds to surface receptors, and triggers potent thrombotic and acute inflammatory events.
• PAF activates inflammatory cells, mediates hypersensitivity, acute inflammatory, and anaphylactic reactions, causes platelets to aggregate and activate, and neutrophils and alveolar macrophages to generate superoxide radicals to kill bacteria.
• PAF also lowers blood pressure and is one of the most potent bioactive molecules known, causing effects at concentrations as low as 10^−11 mol/L.

Sphingophospholipids

• Sphingomyelin is a phospholipid with a backbone of the amino alcohol sphingosine, rather than glycerol.

Phosphatidylserine (PS)

• PS is synthesized in mammalian tissues by the base exchange reaction, in which the ethanolamine of PE is exchanged for free serine.
• PS has a net negative charge and is primarily found on the inner leaflet of the cell membrane.

Phosphatidylinositol (PI)

• PI is synthesized from free inositol and CDP-DAG.
• PI has a net negative charge and is primarily found on the inner leaflet of the cell membrane.
• PI serves as a reservoir of arachidonic acid in membranes and provides the substrate for prostaglandin synthesis when required.

Signal Transduction

• The phosphorylation of membrane-bound PI produces polyphosphoinositides, which play a role in signal transduction across membranes.
• Cleavage of PIP2 by phospholipase C occurs in response to the binding of various neurotransmitters, hormones, and growth factors to G protein-coupled receptors on the cell membrane.

Phosphatidylcholine (PC)

• PC is a major lipid component of lung surfactant, which is the extracellular fluid layer lining the alveoli.
• PC serves to decrease the surface tension of this fluid layer, reducing the pressure needed to reinflate alveoli, thereby preventing alveolar collapse (atelectasis).
• Fetal lung maturity can be gauged by determining the DPPC/sphingomyelin ratio in amniotic fluid.

Lung Maturity

• Respiratory distress syndrome (RDS) in preterm infants is associated with insufficient surfactant production and/or secretion.
• Lung maturation can be accelerated by giving the mother glucocorticoids shortly before delivery to induce expression of specific genes.
• Postnatal administration of natural or synthetic surfactant is also used to treat RDS.

Phosphatidylcholine Synthesis

• PC is synthesized from phosphatidylserine, which is decarboxylated to PE by PS decarboxylase.
• PE then undergoes three methylation steps to produce PC.
• S-adenosylmethionine is the methyl group donor.

Phospholipid Synthesis

• Most phospholipids are synthesized in the smooth endoplasmic reticulum (SER).
• Phospholipids are transported to the Golgi and then to membranes of organelles or the plasma membrane or are secreted from the cell by exocytosis.
• Ether lipid synthesis from dihydroxyacetone phosphate begins in peroxisomes.