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Glycerophospholipids (GPLs)

  • Amphipathic molecules with both hydrophilic and hydrophobic parts.
  • Hydrophilic "head": includes polar phosphate and alcohol groups (such as choline, serine, or inositol).
  • Hydrophobic "tails": long-chain fatty acids (FA).
  • Examples: Phosphatidylcholine has three distinct fatty acid positions: C1, C2, and C3.

Properties of Molecules

  • Hydrophobic Molecules: O extsubscript{2}, CO extsubscript{2}, N extsubscript{2} (small, uncharged).
  • Small Uncharged Polar Molecules: H extsubscript{2}O, glycerol.
  • Large Uncharged Polar Molecules: Glucose, sucrose.
  • Ions: Na extsuperscript{+}, Ca extsuperscript{2+}, K extsuperscript{+}, H extsuperscript{+}.

Phospholipid Bilayers

  • Without Unsaturated Fatty Acids: Low fluidity and permeability.
  • With Unsaturated Fatty Acids: High fluidity and permeability.
  • Temperature Effects:
    • Increased temperature increases fluidity (and vice versa).
  • Cholesterol's Role:
    • Reduces fluidity at the membrane surface.
    • Acts as a spacer to increase fluidity deeper in the lipid bilayer.

Glycolipids

  • Main class contains sphingosine and sugars (glycosphingolipids - GSL).
  • Simplest GSL: ceramide.
  • Particularly abundant in nerve cell membranes, involved in:
    • Nerve impulse transmission
    • Cell-cell recognition
    • Binding with glycoprotein hormones and bacterial toxins.
  • Genetic defects in glycolipid metabolism can cause fatal neurological disorders (sphingolipidoses).

Sphingolipids

  • Membrane lipids based on an 18C amino alcohol: sphingosine.
  • Parent compound: ceramide.
  • Fatty acid attached via amide linkage to the nitrogen of sphingosine.
  • Precursor to sphingomyelin.
  • Carbohydrates addition leads to cerebrosides and gangliosides—important membrane lipids.

Types of Glycosphingolipids

  • Cerebrosides: Ceramide + 1 sugar.
  • Gangliosides: Ceramide + 3 or more sugars (includes N-acetylneuraminic acid).
  • Globosides: Ceramide + 2 or more sugars (excluding N-acetylneuraminic acid).

Sphingolipidoses and Disorders

  • GM1 Gangliosidosis, Tay-Sachs disease, Sandhoff's disease, and Fabry's disease are examples linked to metabolic enzyme deficiencies affecting sphingolipids.
  • Each disorder corresponds to specific lipid accumulations due to enzyme failures (e.g., Hexosaminidase A in Tay-Sachs).

Cholesterol

  • Core structure: three 6-membered rings and one 5-membered ring, with an 8C side chain.
  • Properties: Amphipathic due to a weakly polar –OH group at C3.
  • Comprises 30-40% of plasma membrane lipids, crucial for regulating membrane fluidity.
  • Precursor for steroid hormones and bile salts, including:
    • Mineralocorticoids: aldosterone.
    • Glucocorticoids: cortisol.
    • Androgens: testosterone.
    • Estrogens: estradiol.
    • Progestagens: progesterone.
    • Calciferols: 1,25 dihydroxy vitamin D3.

Summary of Lipids and Their Roles

  • Lipids are primarily hydrophobic and cannot form polymers.
  • Fatty acids are energy-dense, stored compactly compared to carbohydrates.
  • Glycerophospholipids form the lipid bilayer of cell membranes; fluidity influenced by lipid length, saturation, and cholesterol content.
  • Glycolipids are abundant in CNS membranes; cholesterol regulates fluidity and serves as a hormone and bile salt precursor.