Phospholipids & Glycolipids

Phospholipids & Glycolipids

These are complex lipids forming the structural backbone of all biological membranes. They are amphipathic molecules with hydrophilic head groups and hydrophobic fatty acid tails.

Phospholipids

Structure: Glycerol backbone + 2 fatty acids (esterified at C1 and C2) + Phosphate + Polar head group (at C3).

  • Phosphatidylcholine (Lecithin): Most abundant phospholipid. Major component of lung surfactant (dipalmitoylphosphatidylcholine — DPPC). Absent in premature infants → IRDS. Also major component of cell membranes and HDL particles.
  • Phosphatidylethanolamine (Cephalin): Found on inner leaflet of plasma membrane. Important in blood clotting.
  • Phosphatidylserine: Inner leaflet; when flipped to outer leaflet of apoptotic cells, signals phagocytosis.
  • Phosphatidylinositol: Minor component but extremely important in cell signaling. PIP2 cleaved by Phospholipase C → DAG (activates PKC) + IP3 (releases Ca²⁺ from ER).
  • Cardiolipin (diphosphatidylglycerol): Unique to inner mitochondrial membrane; also found in bacteria. Antigen for Wassermann reaction (syphilis test).
  • Plasmalogens: Vinyl ether at C1 instead of ester; abundant in heart, brain, skeletal muscle. Important in myelin.
  • PAF (Platelet Activating Factor): Ether at C1, acetyl at C2; potent mediator of anaphylaxis and inflammation.

Sphingolipids (Sphingomyelin)

Backbone: Sphingosine (not glycerol). Sphingosine + Fatty acid → Ceramide. Ceramide + Phosphocholine → Sphingomyelin. Found abundantly in myelin sheath (protects nerves) and brain. Deficiency of Sphingomyelinase → Niemann-Pick disease (sphingomyelin accumulation in liver, spleen, brain).

Glycolipids

Lipids with one or more sugar residues attached to Ceramide.

  • Cerebrosides: Ceramide + 1 sugar (Glucose → Glucocerebroside; Galactose → Galactocerebroside). Galactocerebroside is major glycolipid of myelin. Gaucher's disease: Glucocerebrosidase deficiency → glucocerebroside accumulates.
  • Sulfatides: Sulfated galactocerebroside; in myelin. Metachromatic leukodystrophy: Arylsulfatase A deficiency.
  • Gangliosides: Ceramide + oligosaccharide chain + sialic acid (N-acetylneuraminic acid, NANA). Found on neuronal cell surfaces; important for cell recognition. Tay-Sachs: Hexosaminidase A deficiency → GM2 ganglioside accumulates.

Phospholipid Metabolism

  • Phospholipase A1: Cleaves C1 fatty acid
  • Phospholipase A2: Cleaves C2 fatty acid (releases Arachidonic acid for eicosanoid synthesis). Inhibited by glucocorticoids (via Lipocortin/Annexin).
  • Phospholipase C: Cleaves head group releasing DAG + Phosphate head
  • Phospholipase D: Cleaves head group from phosphate, releasing PA (phosphatidic acid)

Cell Membrane Structure

Fluid mosaic model: Phospholipid bilayer with embedded proteins. Cholesterol modulates fluidity (too little = too fluid; too much = too rigid). Membrane is asymmetric: Phosphatidylcholine and sphingomyelin on outer leaflet; phosphatidylserine and PE on inner leaflet (maintained by flippases).