Lipoprotein Metabolism Lecture Notes

Introduction

• Lipoprotein metabolism involves the transport of cholesterol and triglycerides within the body.
• Two main pathways:
  • Exogenous Pathway: Transports lipids from the diet.
  • Endogenous Pathway: Involves lipids synthesized within the body.

Exogenous Pathway

Digestive Process

• Triglycerides & Cholesterol: Digested in the small intestine.
• Cholecystokinin (CCK): Released in response to fats, stimulates gallbladder.

Bile and Emulsification

• Gallbladder & Liver: Release bile through ducts into the intestine.
• Bile Composition: Contains bile salts, bilirubin, cholesterol, phospholipids.
• Bile Salts: Aid in emulsification of fats, breaking down big fat globules into smaller droplets.

Pancreatic Lipase

• Enzyme Activation: Breaks triglycerides into monoglycerides and free fatty acids.
• Micelles Formation: Bile salts surround these products along with cholesterol and vitamins (A, D, E, K).

Absorption

• Enterocytes: Absorb monoglycerides and free fatty acids.
• Reformation of Triglycerides: Occurs in the smooth endoplasmic reticulum.

Chylomicrons

• Formation: Combine triglycerides with proteins (ApoB48) and phospholipids.
• Transport: Enter lymphatic system via lacteals, eventually reaching bloodstream.

Function

• Donation of Proteins by HDL: ApoE and ApoC2 are important for further metabolism.
• Lipoprotein Lipase Activation: Facilitates fatty acid entry into tissues.
• Energy Use or Storage: Fatty acids used for ATP in muscles or stored in adipose as triglycerides.

Endogenous Pathway

Liver Synthesis

• VLDL Formation: Triglycerides and cholesterol combine with ApoB100.

VLDL to LDL Transformation

• Lipoprotein Lipase: Converts VLDL to IDL by removing triglycerides.
• IDL Fate: Can return to liver or be further processed to LDL.

LDL

• Peripheral Tissues: Can deliver cholesterol for steroid hormone production.
• Atherogenesis: Excess LDL can oxidize, leading to foam cell formation and atherosclerosis.

HDL

• Reverse Cholesterol Transport: Collects cholesterol from tissues and foam cells.
• Conversion to HDL3 and HDL2: Via uptake of cholesterol.

Cholesterol Utilization

• Bile Salt Formation: Cholesterol can convert to bile salts in the liver.
• Membrane Incorporation: Provides rigidity to cell membranes.

Health Implications

• Cholesterol Levels:
  • Total serum cholesterol should be <200 mg/dL.
  • HDL: Higher is better; 40-50 mg/dL for men, 50-60 mg/dL for women.
  • LDL: Lower is better; ideally <100 mg/dL.

Conclusion

• Lipoprotein metabolism is essential for lipid transport and energy balance.
• Imbalances can lead to cardiovascular diseases like atherosclerosis.

Tips for Further Study

• Understand the role of different apolipoproteins.
• Review the biochemical pathways of triglyceride breakdown and synthesis.
• Study the health effects of altered lipid levels.