Catabolism of Fatty Acids in Exercise

Study Notes

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.

Description

This quiz explores the process of fatty acid catabolism and its significance in energy production during exercise, particularly for long-distance runners. It covers key enzymes, metabolic pathways, and the role of fat oxidation in energy mobilization, enhancing your understanding of human metabolism.