Lipid Metabolism

1. Digestion and Absorption of Lipids

1. Digestion and Absorption of Lipids

• Enzymes Involved: Lipase (pancreatic lipase), phospholipase, and cholesterol esterase.

• Steps:

  1. Emulsification by bile salts.

  2. Hydrolysis of triglycerides into monoglycerides and free fatty acids.

  3. Formation of micelles for absorption in the intestinal cells.

• Clinical Relevance: Disorders like malabsorption syndromes and steatorrhea.

2. Fatty Acid Oxidation (Beta-Oxidation)

2. Fatty Acid Oxidation (Beta-Oxidation)

• Location: Mitochondrial matrix.

• Steps:

  • Activation of fatty acids to acyl-CoA.

  • Transport into mitochondria via the carnitine shuttle.

  • Sequential removal of two-carbon units as acetyl-CoA.

• Energy Yield: Each cycle produces NADH, FADH2, and acetyl-CoA.

• Clinical Relevance: Defects in beta-oxidation enzymes can lead to conditions like medium-chain acyl-CoA dehydrogenase deficiency (MCAD).

3. Fatty Acid Synthesis

Fatty Acid Synthesis

• Location: Cytoplasm.

• Key Enzyme: Fatty acid synthase.

• Steps:

  • Acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase.

  • Sequential addition of two-carbon units to form palmitate.

• Regulation: Insulin promotes synthesis; glucagon inhibits it.

• Clinical Relevance: Dysregulation can contribute to obesity and metabolic syndrome.

4. Triglyceride Metabolism

4. Triglyceride Metabolism

• Synthesis: Esterification of glycerol with fatty acids.

• Breakdown: Lipolysis by hormone-sensitive lipase.

• Clinical Relevance: Hypertriglyceridemia and its role in cardiovascular diseases.

5. Cholesterol Metabolism

5. Cholesterol Metabolism

• Synthesis: Occurs in the liver; HMG-CoA reductase is the rate-limiting enzyme.

• Transport: Lipoproteins (LDL, HDL, VLDL).

• Clinical Relevance: Atherosclerosis, familial hypercholesterolemia.

6. Ketogenesis

6. Ketogenesis

• Location: Liver mitochondria.

• Steps:

  • Conversion of acetyl-CoA into ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone).

• Clinical Relevance: Ketosis in diabetes mellitus and starvation.

7. Regulation of Lipid Metabolism

• Hormonal Control: Insulin, glucagon, epinephrine.

• Enzymatic Regulation: Key enzymes like HMG-CoA reductase, acetyl-CoA carboxylase.

• Clinical Relevance: Dyslipidemia and its management.

7. Regulation of Lipid Metabolism