9 - Chp 23 - FATTY ACID CATABOLISM

Chapter 23: Fatty Acid Metabolism

1. Overview of Fatty Acids for Energy Storage

  • Fats are effective energy storage molecules, constituting ~83% of available energy.

  • Fatty acids are highly reduced, leading to high energy yield upon oxidation compared to carbohydrates and proteins.

  • Energy release from triglycerides (TG) surpasses that of carbohydrates and proteins.

2. Sources of Fatty Acids

2.1 Metabolic Sources

  • Fatty acids originate from:

    • Diet

    • Mobilization of stored fat in adipocytes

    • De novo synthesis (synthesis from scratch)

  • Fatty acid synthesis and degradation are tightly regulated to prevent simultaneous processes.

2.2 Locations of Metabolism

  • Synthesis: cytosol

  • Degradation: mitochondria

3. Fat Cells (Adipocytes)

  • Fat in animals is primarily stored as triglyceride droplets within adipocytes.

  • Metabolic functions of adipocytes include:

    • Accumulation and storage of surplus energy via triacylglycerol synthesis (lipogenesis)

    • Mobilization of lipids by releasing free fatty acids (FFAs) during negative energy balance.

4. Mobilization of Stored Fat

4.1 Mechanisms of Release

  • Fatty acids can be released from lipid droplets through:

    • Lipolysis: Enzymatic breakdown of TGs via triacylglycerol lipase.

    • Lipophagy: Autophagic mechanisms degrading lipids within cells.

5. Hormonal Regulation of Lipolysis

  • Lipolysis in adipose tissue is influenced by hormones such as:

    • Adrenaline/Epinephrine

    • Glucagon

    • Adrenocorticotrophic hormone

  • Hormonal binding induces adenylate cyclase activation, increasing cAMP levels, which activates protein kinase A (PKA) to phosphorylate triacylglycerol lipase leading to fatty acid release.

6. Storage-Lipid Bodies Formation

  • Lipid bodies from the endoplasmic reticulum (ER) associate with adipose-differentiation-related protein (ADRP) and perilipin for storage.

  • Lipid bodies undergo fusion to achieve a mature size.

  • PKA activation promotes perilipin phosphorylation, enabling hormone-sensitive lipase (HSL) to hydrolyze stored lipids.

7. Transport of Lipids in Plasma

  • Mobilized FFAs (unesterified) diffuse across adipocyte membranes into the bloodstream, binding to plasma albumin due to low solubility.

  • Albumin has high-affinity binding sites that protect fatty acid tails from surrounding water.

8. Fatty Acid Binding Proteins (FABPs)

  • FABPs control fatty acid trafficking in cells, functioning as lipid chaperones to transport lipids to specific organelles.

  • They regulate lipid balance, signaling, and delivery of ligands to the nucleus.

9. Digestion and Absorption of Lipids

9.1 Initial Digestion Steps

  • In the duodenum, pancreatic lipases hydrolyze fatty acids at C-1 and C-3 positions.

  • Gastric lipase and lingual lipase in the mouth and stomach initiate triglyceride digestion.

10. Micelle Formation and Bile Functions

  • Released fatty acids combine with bile to form mixed micelles, essential for fat-soluble vitamin absorption (A, E, K).

  • Bile constituents include bile acids, cholesterol, phospholipids, and bilirubin.

11. Bile Acid Functions

  • Bile acids enhance the solubilization and emulsification of lipids, increasing their digestibility by pancreatic lipase.

12. Ketone Bodies and Ketogenesis

  • During fasting, acetyl CoA from fatty acid breakdown converts to ketone bodies (acetone, acetoacetate, beta-hydroxybutyrate) in the liver.

  • Ketone bodies serve as alternative fuel for the brain, heart, and muscle, particularly during starvation.

13. Energy Yield from Fatty Acid Oxidation

  • Complete beta-oxidation of palmitic acid yields a net of 106 ATP, factoring in ATP consumption during fatty acid activation.

14. Types of Fatty Acid Oxidation

14.1 Odd-Carbon Fatty Acids

  • Odd-carbon fatty acids are converted to succinyl-CoA via carboxylation and epimerization reactions, enabling entry into the TCA cycle.

14.2 Unsaturated Fatty Acids

  • Mono-unsaturated undergo typical beta-oxidation but require enoyl-CoA isomerization.

  • Polyunsaturated acids face additional steps leading to less energy yield compared to saturated acids.

15. Alternative Fatty Acid Oxidation

  • Other pathways for fatty acid oxidation include peroxisomal beta-oxidation, branched-chain alpha-oxidation, and omega-oxidation, especially when beta-oxidation is defective.

16. Adipocyte Variants: White, Beige, Brown

  • Adipose tissue functions as an endocrine organ, composed of white, beige, and brown adipocytes, each with distinct genetic and functional characteristics.

  • White fat stores energy, while brown fat is involved in thermogenesis, utilizing uncoupling protein UCP1 to dissipate heat.

17. Thermogenesis Mechanisms

  • Brown fat thermogenesis is critical in newborns and hibernating animals, regulated by UCP1 following cold exposure or adrenal stimulation.

  • Beige adipocytes can arise from white adipocytes and also contribute to thermogenic responses.