24.3 Lipid Metabolism

Lipid metabolism is crucial for energy production and storage in the body. It involves breaking down fats for fuel and creating new fats when energy is abundant. This process helps maintain energy balance and provides alternative fuel sources during fasting.

Lipids play diverse roles beyond energy, including hormone production and cell membrane structure. Understanding lipid metabolism sheds light on how the body adapts to different nutritional states and maintains overall health.

Lipid Metabolism

Energy extraction from fats

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• Triglycerides are the primary form of stored fat in the body composed of three fatty acids attached to a glycerol backbone (e.g., saturated fats, unsaturated fats)
• Lipolysis breaks down triglycerides into free fatty acids and glycerol in adipose tissue stimulated by hormones such as glucagon and epinephrine (adrenaline)
• Beta-oxidation process breaks down fatty acids to generate energy in the mitochondria of cells
  • Fatty acids are converted into acetyl-CoA which enters the citric acid cycle (Krebs cycle)
  • Each cycle of beta-oxidation produces NADH and FADH2 used in the electron transport chain to generate ATP (cellular energy currency)

Ketogenesis in energy production

• Ketogenesis produces ketone bodies from fatty acids in the liver when glucose availability is limited during fasting or low-carbohydrate diets (ketogenic diets)
  • Acetyl-CoA from beta-oxidation is converted into ketone bodies acetoacetate, beta-hydroxybutyrate, and acetone
• Ketone bodies serve as an alternative energy source for tissues, especially the brain which cannot directly utilize fatty acids for energy
  • Ketone bodies can cross the blood-brain barrier and provide energy for the brain during glucose scarcity (e.g., during prolonged fasting)

Ketone body utilization in tissues

• Ketone bodies are released from the liver and transported through the bloodstream to target tissues (e.g., brain, heart, skeletal muscle)
• In target tissues, ketone bodies are converted back into acetyl-CoA:
  1. Acetoacetate is converted into acetoacetyl-CoA by the enzyme succinyl-CoA:3-ketoacid CoA transferase (SCOT)
  2. Acetoacetyl-CoA is then split into two molecules of acetyl-CoA by the enzyme thiolase
• Acetyl-CoA enters the citric acid cycle to generate NADH and FADH2 for ATP production via the electron transport chain
• Ketone body utilization maintains energy homeostasis during periods of glucose scarcity by providing an alternative energy source for the brain and other tissues and sparing glucose for tissues that rely on it as their primary energy source

Lipogenesis process and regulation

• Lipogenesis synthesizes fatty acids and triglycerides from excess carbohydrates primarily in the liver and adipose tissue to store excess energy as triglycerides for future use
• Key steps of lipogenesis:
  1. Acetyl-CoA is produced from excess glucose through glycolysis and the pyruvate dehydrogenase complex
  2. Acetyl-CoA is converted into malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC)
  3. Fatty acid synthase (FAS) catalyzes the formation of palmitic acid (a 16-carbon fatty acid) from malonyl-CoA and acetyl-CoA
  4. Palmitic acid undergoes elongation and desaturation to form various fatty acids (e.g., stearic acid, oleic acid)
  5. Fatty acids are esterified with glycerol to form triglycerides
• Regulation of lipogenesis:
  • Insulin stimulates lipogenesis by activating ACC and FAS
  • Glucagon and epinephrine inhibit lipogenesis by inactivating ACC and FAS
  • Dietary factors such as high-carbohydrate intake can promote lipogenesis

Lipid Transport and Metabolism

• Lipoproteins are complex particles that transport lipids through the bloodstream
• Cholesterol is a crucial component of cell membranes and serves as a precursor for steroid hormones
• Bile acids, synthesized from cholesterol in the liver, aid in the digestion and absorption of dietary fats
• Phospholipids are essential components of cell membranes, contributing to membrane fluidity and function