In-Depth Notes on Lipid Metabolism

Lipids as Energy Storage

  • Lipids are excellent storage forms of energy.
    • High energy density: They are highly reduced structures, yielding twice the energy from oxidation compared to carbohydrates and proteins.
    • Non-polarity: Do not change the osmolarity of a cell.
    • Chemical inertness: Prevent unwanted chemical reactions.

Limitations of Lipid Storage

  • Lipids must be solubilized first before water-soluble enzymes can act on them.
  • The carbons of lipids must be converted to a chemically activated form for catabolism.

Sources of Fatty Acid Fuels

  • Three primary sources:
    • Dietary fats
    • Stored fats
    • Fats synthesized in other organs.

Absorption of Fats

  • Occurs in the small intestine.
    • Aids in the conversion of macroscopic fat particles to microscopic micelles.
    • Bile salts assist this transformation, prominently taurocholic acid.

Role of Lipases in Fat Absorption

  • Intestinal lipases facilitate fat absorption by acting on the surface of water-micelle interfaces.
  • Fatty acids and breakdown products absorbed by the intestinal mucosa are then converted back into triacylglycerols.

Transport of Lipids

  • Lipids are transported as protein complexes, which include:
    • Chylomicrons that transport dietary lipids.
    • Apolipoproteins (such as ApoC-II) play critical roles in lipid metabolism and regulation.

Types of Lipoproteins

  • Five major classes of lipoproteins, characterized by:
    • Density
    • Particle diameter
    • Protein and lipid composition.
    • Chylomicrons: <0.95 g/cm³, largest diameter, high in triacylglycerols.
    • VLDL (Very Low-Density Lipoprotein), LDL (Low-Density Lipoprotein), IDL (Intermediate-Density Lipoprotein), HDL (High-Density Lipoprotein): differences in density, composition.

Lipoprotein Lipase Activation

  • Lipoprotein lipase is activated by ApoC-II, which facilitates the conversion of triacylglycerols into fatty acids and glycerol through hydrolysis.

Fatty Acid Oxidation

Pathways of Fatty Acid Oxidation:
  1. Carnitine Shuttle: Required for fatty acids to enter mitochondria for oxidation.
  2. Fatty acids undergo β-oxidation in the mitochondrion to yield Acetyl-CoA.

Steps of Beta-Oxidation

  • Fatty acids are oxidized in a series of steps that resemble TCA cycle reactions, including:
    1. Dehydrogenation: Production of trans-Δ2-enoyl CoA.
    2. Hydration: Formation of L-β-Hydroxyacyl-CoA.
    3. Dehydrogenation: Production of β-Ketoacyl-CoA.
    4. Thiolysis: Formation of Acyl-CoA and Acetyl-CoA.

Regulation of Fatty Acid Metabolism

  • Feedback regulation involving levels of intermediates (like Acetyl-CoA and Malonyl-CoA), glucose, and hormones (e.g. glucagon, insulin).

Ketogenesis

  • Ketone bodies are produced from excess acetyl-CoA, especially during prolonged fasting or carbohydrate-restricted diets, providing an alternative energy source for tissues like the brain and muscles.

Fatty Acid Biosynthesis

  • Fatty acid synthesis primarily occurs in the cytoplasm.
    • Involves Acetyl-CoA and Malonyl-CoA as building blocks, utilizing NADPH as an electron donor.
    • Cycles through condensation, reduction, dehydration, and another reduction to elongate carbon chains.