Catabolism of Fatty Acids in Exercise

Catabolism of Fatty Acids

• Catabolism of fatty acids is a crucial process for energy production, especially during sustained exercise like marathons.
• Sprinters primarily rely on glycolysis and the citric acid cycle (anaerobic processes) for energy, while marathon runners depend on oxidizing fats for longer durations.
• Fatty acid metabolism involves transporting hydrophobic fats through a hydrophilic body, extracting energy from fats, and utilizing an alternate system for transporting broken-down fats through the blood (using ketone bodies).
• Stored fats are mobilized when needed, notably during periods of low glucose availability.
• The mobilization process involves a series of enzymes, including hormone-sensitive lipase (HSL) and adipose triacylglycerol lipase (ATGL), which break down triacylglycerols and release fatty acids.
• Different enzymes, locations, and processes are involved in the activation, transport, and oxidation of fatty acids.
• Fatty acids are activated before catabolism; an enzyme (acyl-CoA synthetase) adds coenzyme A to the fatty acid, requiring ATP.
• Long-chain fatty acids enter the mitochondria as carnitine derivatives via three enzymes (carnitine acyltransferase-I, carnitine-acylcarnitine translocase, and carnitine acyltransferase-II).
• Beta-oxidation is a key process, involving four chemical steps: dehydrogenation, hydration, dehydrogenation, and acyl transfer. These steps release acetyl-CoA which enters the citric acid cycle.
• Beta-oxidation repeatedly cleaves acetyl-CoA, yielding NADH and FADH2 (electron carriers), along with numerous acetyl-CoA molecules, which contribute energy through the citric acid cycle and oxidative phosphorylation.
• Oxidation of fatty acids with odd numbers of carbons follows a slightly altered pathway, producing propionyl-CoA, which eventually enters the citric acid cycle.
• Unsaturated fatty acids require modified beta-oxidation pathways to manage double bonds.
• Some beta-oxidation occurs in peroxisomes for very long-chain fatty acids.
• Diseases like X-linked adrenoleukodystrophy arise from defects in peroxisomal beta-oxidation.
• The oxidation of fatty acids is tightly regulated, mainly by controlling their entry into mitochondria
• Malonyl-CoA, an intermediate in fatty acid synthesis, inhibits carnitine acyltransferase I, thus preventing fatty acid entry into mitochondria, which maintains the balance of fatty acid synthesis and breakdown.
• When fatty acid oxidation in the liver exceeds the citric acid cycle's capacity, excess acetyl-CoA is converted into ketone bodies (acetone, acetoacetate, and D-β-hydroxybutyrate) as an alternative energy source for other tissues.
• Overproduction of ketone bodies can lead to acidosis in cases like untreated diabetes.

Glycolysis/Gluconeogenesis

• The glycerol backbone of triacylglycerols is metabolized via glycerol-3-phosphate, dihydroxyacetone phosphate, and glyceraldehyde 3-phosphate. These intermediates are shared by glycolysis/gluconeogenesis.

Citric Acid Cycle (Krebs Cycle)

• The citric acid cycle is a critical metabolic pathway that fully oxidizes acetyl-CoA to produce CO2, NADH, FADH2, and GTP/ATP.

ATP Production from Fatty Acid Oxidation

• Complete palmitic acid (16C) oxidation yields a substantial amount of ATP molecules. 

The Role of Ketone Bodies

• Ketone bodies are crucial alternative energy sources during periods of low glucose availability. 

Genetic Defects in Fatty Acyl-CoA Dehydrogenases

• Defects in fatty acyl-CoA dehydrogenase enzymes can lead to serious diseases like MCAD deficiency (affecting medium-chain fatty acids).  

Homework Questions

• These questions pertain to the effects of high-fat diets without carbohydrates on fat utilization, and the relative advantages of odd vs. even numbered fatty acids under carbohydrate-free conditions.
• Additional questions concern fuel reserves in adipose tissue, comparative studies of energy generation pathways in birds differing in metabolic requirements, and issues related to carnitine deficiency.