Ch 17 - Fatty Acid Catabolism

Chapter 17: Fatty Acid Catabolism

Author: Allyn Ontko, PhD, Department of Chemistry & Physics, Arkansas State University

Introduction to Fatty Acids

  • Fats in Foods: Fats are predominantly stored as triacylglycerols (TAGs), which are esters formed from glycerol and three fatty acid molecules.

  • Composition: TAGs feature a glycerol backbone linked to three fatty acid chains that can differ in length and saturation.

  • Examples of Fatty Acids:

    • Stearoyl (C18:0)

    • Linoleoyl (C18:2, omega-6)

    • Palmitoyl (C16:0)

Fatty Acid Sources

  • Sources of Fatty Acids:

    • Dietary Fat: These are fats obtained from food sources, such as oils, butter, and animal fats.

    • Stored Fat: Triacylglycerides stored in adipose tissue and adipocytes act as a crucial energy reserve.

    • Synthesized Fat: The liver produces fatty acids from surplus dietary sugars through lipogenesis, converting excess glucose into fatty acids for metabolic transport to other organs.

Absorption and Transportation of Fatty Acids

  • Ingestion: Dietary fats are emulsified by bile salts in the small intestine, promoting the formation of mixed micelles to facilitate fat absorption.

  • Enzymatic Breakdown:

    • Lipoprotein lipase: This enzyme breaks down triacylglycerols into fatty acids and glycerol.

    • Intestinal Lipases: Activated by apoC-II, these enzymes further assist in fat digestion.

  • Transport:

    • Chylomicrons: These lipoprotein particles ferry fatty acids through the lymphatic system and bloodstream to target tissues.

    • The intestinal mucosa transforms dietary fats into triacylglycerols, which are subsequently packed into chylomicrons for distribution.

Lipoproteins and Their Components

  • Chylomicrons:

    • Comprising apolipoproteins B-48, C-III, and C-II.

    • They consist of phospholipids, cholesterol, and triacylglycerols, functioning as carriers for dietary lipids.

Hepatic Cycle for Fatty Acid Mobilization

  • Processes in Hepatocytes:

    • Lipid transport comprises interactions between lipids and blood capillaries, accompanied by conformational changes.

  • Lipoproteins: Key lipoproteins include VLDL (very low-density lipoprotein), LDL (low-density lipoprotein), and HDL (high-density lipoprotein), all essential for regulating lipid metabolism and transport.

Hormonal Regulation of Fatty Acid Mobilization

  • Hormones such as glucagon and epinephrine trigger the breakdown of stored fats (lipolysis).

  • Mechanism: Upon hormone binding to receptors, adenylyl cyclase is activated, increasing cAMP levels, which activates protein kinase A (PKA) and phosphorylates hormone-sensitive lipase to commence the breakdown of triacylglycerols into free fatty acids for oxidation.

Glycerol Metabolism in Glycolysis

  • Glycerol can be converted into glycerol-3-phosphate, entering the glycolytic pathway.

  • Enzymatic steps: Phosphorylation and oxidation lead to the formation of dihydroxyacetone phosphate, an intermediate in glycolysis.

Fatty Acid Transport into Mitochondria

  • Transportation Mechanism:

    • Short-chain fatty acids (<12 carbons) can readily diffuse through mitochondrial membranes.

    • Long-chain fatty acids (≥14 carbons) utilize the carnitine shuttle:

      • They are converted into acyl-carnitine by carnitine acyltransferase.

      • Acyl-carnitine then crosses the mitochondrial membrane, where it is reconverted to fatty acyl-CoA for subsequent metabolism.

Beta-Oxidation of Fatty Acids

  • Fatty acids undergo beta-oxidation by removing two-carbon units as acetyl-CoA sequentially.

  • Stages of Oxidation:

    • Stage 1: Activation of fatty acids to fatty acyl-CoA, which requires ATP.

    • Stage 2: Transport into the mitochondrial matrix follows the acyl-carnitine pathway.

    • Stage 3: The repeated cycles of beta-oxidation remove two-carbon acetyl-CoA units from the activated fatty acid chain.

  • Key Enzymes: Significant enzymes include acyl-CoA dehydrogenase, enoyl-CoA hydratase, and beta-hydroxyacyl-CoA dehydrogenase, each facilitating distinct steps of the oxidation cycle and regenerating CoA.

Yield of ATP from Palmitoyl-CoA Oxidation

  • The complete oxidation of one molecule of Palmitoyl-CoA can yield a total of 108 ATP.

  • This ATP yield is derived from energy produced during beta-oxidation and subsequent pathways, including the citric acid cycle, involving additional enzymes such as various dehydrogenases.

Regulation of Fatty Acid Oxidation

  • Insulin and glucagon levels play significant roles in modulating fatty acid oxidation pathways:

    • High carbohydrate diets lead to increased esterification of fatty acids into TAGs for storage.

    • Low carbohydrate conditions promote fatty acid oxidation as the body shifts from glucose to fatty acids as its energy source.

Dealing with Monounsaturated and Polyunsaturated Fats

  • Monounsaturated fats require isomerases to convert to suitable forms for entry into the beta-oxidation pathway.

  • Polyunsaturated fats necessitate both isomerases and reductases for appropriate metabolism during oxidation.

Fatty Acids with Odd-Numbered Carbons

  • Odd-chain fatty acids require further enzymatic steps in the beta-oxidation cycle, ultimately leading to the production of succinyl-CoA, which can enter the citric acid cycle for energy generation.

Formation of Ketone Bodies

  • Ketone bodies are synthesized in the liver when carbohydrate intake is low, providing alternative energy sources.

  • Types of Ketone Bodies: These include acetone, acetoacetate, and D-β-hydroxybutyrate.

  • These compounds are vital during low glucose availability, particularly for sustaining brain function during extended fasting and diabetes.

Conclusion

  • Bottom Line: Fatty acid metabolism includes a variety of metabolic pathways, such as oxidation, synthesis, and the creation of vital energy molecules.

  • Variations in dietary habits and metabolic states influence energy homeostasis and overall metabolism, highlighting the importance of balanced lipid intake for health maintenance.