Lipid Transport and Lipoprotein Structure

Lipid Transport

• Lipids are insoluble in water, associating with proteins to form lipoproteins, which are water-soluble.
• The protein portion of lipoproteins is called apolipoprotein.
• Lipoproteins transport lipids between various tissues.
• Total plasma lipid is 400-600 mg/dL, comprising triacylglycerol (20%), phospholipids (30%), cholesterol (40%), and free fatty acids.

Lipoprotein Structure

• Lipoproteins consist of a core of nonpolar lipids (triacylglycerol and cholesterol esters) and a surface layer of phospholipids and cholesterol.
• A portion of the lipoprotein is composed of apolipoproteins (apoproteins, or Apo).
• Apolipoproteins range from 1% in chylomicrons to 60% in some high-density lipoproteins (HDLs).
• Some apolipoproteins, exist as integral structural elements, while others as peripheral elements.

Lipoprotein Classification

• Lipoprotein density increases with the protein content.
• Lipoproteins are categorized by their density using ultracentrifugation and electrophoresis.
  • Chylomicrons
  • Very low-density lipoproteins (VLDL or pre-β-lipoprotein)
  • Intermediate-density lipoproteins (IDL)
  • Low-density lipoproteins (LDL or β-lipoprotein)
  • High-density lipoproteins (HDL or α-lipoprotein)
• Lipoprotein (a) (Lp(a)) has a similar lipid composition to LDL. It competes with plasminogen for tissue plasminogen receptors.
• The predominant lipid in chylomicrons and VLDL is triacylglycerol (TAG).
• The predominant lipid in LDL is cholesterol.
• The predominant lipid in HDL is phospholipid.

Apolipoproteins

• Apolipoproteins are proteins associated with lipoproteins.
• Five major classes: A to E.
• Apo B is found in two forms: apo B-100 and apo B-48.
  • Apo B-100 is present in LDL.
  • Apo B-48 is found in chylomicrons.
• Apo (a) is present in Lp(a) and contains high carbohydrate content.

Apolipoprotein functions

• Promotes the solubility of lipids in plasma.
• Enhances the stability of lipoprotein particles.
• Acts as ligands for interactions with lipoprotein receptors on tissues, regulating tissue uptake of lipids.

Apolipoproteins as enzyme activators or inhibitors

• Some apolipoproteins act as enzyme activators or inhibitors.
  • Activators:
    • C-II for lipoprotein lipase.
    • A-I for lecithin:cholesterol acyltransferase (LCAT).
  • Inhibitors:
    • ApoA-II and apoC-III for lipoprotein lipase.
    • apoC-I for cholesteryl ester transfer protein.

Chylomicron Metabolism

• Site of synthesis: Intestinal mucosa.
• Function: Transports dietary lipids from the intestine to peripheral tissues.
• Structure: Primarily triacylglycerol (98%), with 1-2% proteins (apo B-48, E, and C-II)
• Half-life: Approximately 1 hour.

Very Low-Density Lipoprotein (VLDL) Metabolism

• Site of synthesis: Liver
• Function: Transports endogenously synthesized lipids from the liver to peripheral tissues.
• Structure: Primarily triacylglycerol, with 10% proteins (apo B-100, E, and C-II)
• Half-life: 1-3 hours.

Intermediate-Density Lipoprotein (IDL) Formation

• Lipoprotein lipase (LpL) action leads to TAG loss, resulting in VLDL remnants.
• These remnants are known as intermediate-density lipoproteins (IDL).
• IDL contains decreased TAG and increased cholesterol.
• IDL is either taken up by the liver or converted to low-density lipoproteins (LDL).