Lecture 3: Lipid Metabolism

Key Concepts

Lipoproteins

• Definition: Combination of lipids and proteins for lipid transport.
• Structure:
  • Proteins (e.g., APO B 100, APO C2, APOE) on the outside.
  • Non-polar lipids inside.
  • Amphipathic lipids (e.g., phospholipids) with non-polar tails and polar heads surrounding them.
• Four classes of Lipoproteins:
  • Chylomicrons:
    • Form in intestinal mucosal cells.
    • Transport dietary fat (exogenous).
    • Activate enzyme allowing fatty acid absorption.
  • Very Low-Density Lipoproteins (VLDLs):
    • 10% protein content.
    • Transport endogenous triglycerides from liver to fat cells.
    • Converted to LDLs.
  • Low-Density Lipoproteins (LDLs):
    • Known as "bad cholesterol."
    • 25% protein content.
    • Carry 75% of blood cholesterol to body cells.
    • Contains APO B 100 for receptor-mediated endocytosis.
  • High-Density Lipoproteins (HDLs):
    • Known as "good cholesterol."
    • 40% protein content.
    • Carry cholesterol from cells to liver for elimination.

Cholesterol

• Sources:
  • Endogenous: Synthesized by liver.
  • Exogenous: From outside sources.
• Desirable levels for adults:
  • Total cholesterol: <200 mg/dL
  • LDL: <130 mg/dL
  • HDL: >40 mg/dL
  • Triglycerides: 10-190 mg/dL

Reducing Blood Cholesterol

• Methods:
  • Exercise and diet.
  • Drugs to inhibit cholesterol synthesis or absorption.

Fate of Lipids

• Oxidation: Produces ATP.
• Storage: In adipose tissue.
• Structural Usage: For essential molecules like phospholipids, lipoproteins.
• Triglycerides Storage:
  • Mainly in subcutaneous layer.
  • Also near kidneys, omentum, genital area, and between muscles.

Lipid Processes

• Lipolysis:
  • Breakdown of triglycerides into fatty acids and glycerol.
  • Influenced by hormones: epinephrine, norepinephrine, glucocorticoids.
  • Glycerol and fatty acids processed separately.
• Beta Oxidation:
  • Fatty acids converted to acetyl-CoA, entering Krebs cycle.
  • Formation of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, acetone).
  • Ketogenesis: Heart and kidney prefer acetoacetic acid for ATP.
• Lipogenesis:
  • Conversion of glucose/amino acids to lipids, stimulated by insulin.
  • Involves glyceraldehyde-3-phosphate and acetyl-CoA.

Ketone Bodies and Ketosis

• Ketosis: High levels of ketone bodies can result in acidosis (ketoacidosis).
• Triggers: Fasting, high-fat diets, like the Atkins diet.
• Symptoms: Sweet smell (acetone) on breath.
• Implications for Diabetics: Due to impaired glucose uptake, increased use of fats for fuel.

Goals for Lecture

• Describe chylomicrons, my cells, VLDL, HDL, LDL.
• List sources of cholesterol.
• Outline normal blood cholesterol levels.
• Discuss methods to lower blood cholesterol.
• Define lipolysis, lipogenesis, ketone bodies, and ketoacidosis.