Wk 9&10 Lecture 3: Fatty Acid Degradation, ATP Production and Glucogneogenesis

Introduction

• Continuing discussion on Soudi's marathon biochemistry at the Olympics.

• Current progress at the 38-kilometer mark, exceeding expectations.

Soudi's Performance

• Clocking at 310 meters per minute.

• Increasing utilization of fatty acids as fuel while decreasing glycogen use.

• Overview of ATP generation from fatty acids.

Fatty Acid Metabolism

Beta Oxidation Pathway

• ATP Generation from Fatty Acids:

  • Fatty acids converted to acetyl CoA.

  • Importance for endurance activities.

• Glycerol Utilization:

  • Breakdown of fats maintains blood glucose levels (gluconeogenesis).

Previous Lecture Recap

• Effects of adrenaline and glucagon on fat stores.

• Activation of fatty acids into fatty acyl CoA in the mitochondria.

Process of Beta Oxidation

1. Activating fatty acids:

   • Fatty acids converted into fatty acyl CoA.

   • Prepared for beta oxidation in the mitochondria.

2. Conversion steps:

   • Fatty acids produce molecules of acetyl CoA through beta oxidation.

   • Reduced coenzymes NADH and FADH2 generated for ATP production.

Detailed Steps of Beta Oxidation

• First Reaction: Acyl CoA dehydrogenase catalyzes the reaction, producing FADH2 and introducing a double bond.

• Second Reaction: Hydrotase adds water across the double bond to form 3-hydroxyacyl CoA.

• Third Reaction: Dehydrogenase converts the hydroxyl group at the beta carbon to a keto group, yielding 3-ketoacyl CoA, and forms NADH.

• Fourth Reaction: Thiolase uses CoA to release acetyl CoA and shortens the fatty acyl chain.

Results of Beta Oxidation

• One round of breakdown yields:

  • 1 molecule of acetyl CoA,

  • 1 molecule of NADH,

  • 1 molecule of FADH2.

• Example with Palmitoyl CoA (16 carbons):

  • Undergoes 7 rounds of beta oxidation to produce 8 acetyl CoA molecules.

Energy Yield Analysis

• ATP Production:

  • From 7 NADH and 7 FADH2 during beta oxidation.

  • Generating 28 ATP and producing 35 water molecules.

• Total Water Production:

  • Water generated from the complete oxidation of fatty acid exceeds that from glucose.

Role of the Liver

Glucose Production during the Marathon

• Liver maintains blood glucose levels during exercise, utilizing stored glycogen and gluconeogenesis from glycerol.

• Effects of Adrenaline and Glucagon:

  • Stimulates liver glycogen breakdown and gluconeogenesis.

  • Fatty acids become a major fuel source.

Glycerol and Gluconeogenesis

• Glycerol from fat breakdown aids glucose levels.

• Conversion requires multiple enzymes and energy investment:

  • Uses ATP and GTP.

  • Involves specific enzymes to bypass irreversible glycolytic steps.

Regulation of Metabolic Pathways

• Reciprocal regulation between gluconeogenesis and glycolysis.

• Gluconeogenesis relies on glycerol; lactate also plays a role.

• AMPK and PKA regulate pathways based on cellular energy status.

• Fructose 2,6-bisphosphate regulates key enzymes.

Conclusion

• Fatty acid metabolism benefits endurance and hydration.

• Soudi maximizes energy utilization and hydration as she approaches the finish line.

• Final Stretch: Inspired by crowd cheers, Soudi surges ahead and wins the race.