Fatty Acid Catabolism and Lipolysis

Triacylglycerol (TAG) and Fatty Acid Catabolism

• Purpose: Provides energy during fasting or increased energy demand. This involves lipolysis (TAG breakdown) and beta-oxidation (FA breakdown).

Lipolysis

• Definition: Breakdown of triacylglycerols into glycerol and free fatty acids (FFAs).
• Location: Adipose tissue.
• Hormonal Regulation: Stimulated by glucagon, epinephrine, and norepinephrine; inhibited by insulin. These hormones activate hormone-sensitive lipase (HSL) through cyclic AMP-dependent protein kinase (PKA).
• Enzymatic Steps:
  • Adipose triglyceride lipase (ATGL): Converts triacylglycerol (TAG) to diacylglycerol (DAG).
  • Hormone-sensitive lipase (HSL): Converts DAG to monoacylglycerol (MAG).
  • Monoacylglycerol lipase (MAGL): Converts MAG to glycerol + a free fatty acid (FFA).
• Products:
  • Glycerol: Transported to the liver for gluconeogenesis or glycolysis.
  • Free Fatty Acids (FFAs): Bind to albumin in the blood and are transported to energy-demanding tissues.

Beta-Oxidation of Fatty Acids

• Definition: Stepwise removal of two-carbon units (as acetyl-CoA) from fatty acids for energy production.
• Location: Mitochondrial matrix. Long-chain fatty acids are first activated in the cytoplasm.
• Activation: Fatty acid + CoA + ATP → Acyl-CoA + AMP + PPi. Enzyme: Acyl-CoA synthetase (thiokinase).
• Transport into Mitochondria: The carnitine shuttle system moves acyl-CoA into the mitochondrial matrix:
  • CPT I (carnitine palmitoyltransferase I): Converts acyl-CoA to acyl-carnitine (rate-limiting step).
  • Acyl-carnitine is transported into the matrix by a translocase.
  • CPT II regenerates acyl-CoA in the matrix.
• Beta-Oxidation Steps (spiral pathway):
  • Oxidation: Acyl-CoA dehydrogenase forms a double bond; FAD → FADH₂.
  • Hydration: Enoyl-CoA hydratase adds water.
  • Oxidation: β-hydroxyacyl-CoA dehydrogenase forms NADH.
  • Cleavage: Thiolase produces acetyl-CoA and a shortened acyl-CoA.
• Energy Yield per Cycle: 1 FADH₂ → 1.5 ATP; 1 NADH → 2.5 ATP. Each acetyl-CoA formed enters the citric acid cycle.
• Complete Oxidation Example (Palmitic Acid, C16): 7 cycles of beta-oxidation yield 7 FADH₂, 7 NADH, and 8 acetyl-CoA producing a total of 106 ATP (after accounting for activation energy).
• Regulation:
  • Lipolysis: Stimulated by glucagon and epinephrine; inhibited by insulin.
  • Beta-Oxidation: Inhibited by malonyl-CoA (which prevents CPT I activity during FA synthesis); stimulated by high FA availability and fasting state.

This quiz covers the processes of fatty acid catabolism, focusing on triacylglycerol breakdown and lipolysis. You'll learn about the hormonal regulation and enzymatic steps involved in these metabolic pathways. Gain insights into the role of fatty acids and glycerol in energy production during fasting.