Week_9_-_Beta_Oxidation

Oxidative Metabolism of Lipids

  • Focuses on the breakdown and utilization of lipids in liver and muscle.

Page 1: Introduction to Beta-Oxidation

  • Beta-oxidation: process of fatty acid catabolism, primarily oxidative.

  • Involves sequentially removing two-carbon units from fatty acids.

  • Occurs in mitochondria and provides energy in the form of ATP.

Page 2: Beta-Oxidation Process

  • Sequence of reactions involving:

    • Acyl-CoA dehydrogenase: Converts acyl-CoA to trans-enoyl-CoA using FAD.

    • Hydroxyacyl-CoA dehydrogenase: Converts to B-hydroxyacyl-CoA using NAD+.

    • Thiolase: Forms acetyl-CoA and a new acyl-CoA.

  • Produces energy and reducing equivalents (FADH2, NADH).

Page 3: Energy Source of Fat

  • Triglycerides: major form of energy storage in adipose tissue.

  • Main energy source during fasting or prolonged exercise.

  • Catabolism is specifically oxidative through beta-oxidation.

Page 4: Understanding Fatty Acids

  • Fatty acids characterized by hydrophobic chains and a hydrophilic carboxyl group.

  • Trans fatty acids: linear structure, behave similar to saturated fatty acids.

  • Cis fatty acids: cause kinks in the structure, affecting membrane fluidity.

    • Examples: Stearic acid (saturated), Elaidic acid (trans), Oleic acid (cis).

Page 5: Notation of Fatty Acids

  • Fatty acids labeled by carbon number:

    • Saturated: Myristic (14:0), Palmitic (16:0), Stearic (18:0).

    • Unsaturated: Oleic (18:1), Linoleic (18:2).

    • Sources: coconut oil, marine oils, most plant fats.

Page 6: Digestive Overview of Fats

  • Fats are broken down in:

    • Mouth: minor digestion via lingual lipase.

    • Stomach: gastric lipase facilitates additional breakdown.

    • Small intestine: major site of emulsification and enzymatic digestion with bile salts and pancreatic lipase.

Page 7: Integration of Fats in Digestion

  • Dietary triglycerides enter small intestine intact.

  • Short-chain fatty acids travel directly to the liver, while longer ones are absorbed into chylomicrons after processing.

Page 8: Composition of Chylomicrons

  • Composed mainly of triacylglycerol (82%), along with phospholipids, cholesteryl esters, and proteins.

Page 9: Moving Fatty Acids in Cells

  • Process of conversion to fatty acyl-CoA:

    • Fatty acid + ATP → fatty acyl-CoA via acyl-CoA synthetase.

  • Carnitine shuttle facilitates transport into mitochondria.

Page 10: Sites of Beta-Oxidation

  • Peroxisomes: breakdown very long chain fatty acids (>22 Carbons).

  • Mitochondria: metabolize long (14-20) and medium chains (2-12).

Page 12: End Products of Beta-Oxidation

  • The yield of Beta-oxidation in the liver & muscle includes:

    • Acetyl CoA, FADH2, NADH + H+.

    • Ketone bodies produced in liver.

Page 13: Release and Transport of Fatty Acids

  • Fatty acids released from adipose tissue by hormone-sensitive lipase in response to glucagon/epinephrine.

  • Transported via blood bound to albumin.

Page 16: Activation of Fatty Acids

  • Requires ATP and catalyzed by fatty acid acyl CoA synthase (or thiokinase).

  • Important for preparation for beta-oxidation.

Page 19: Carnitine Shuttle Mechanism

  • CPT-1 (Carnitine palmitoyl transferase-1): transfers fatty acids to carnitine for mitochondrial entry.

  • CPT-2 recycles carnitine, facilitating the process.

Page 23: Steps of Beta-Oxidation

  1. Acyl-CoA dehydrogenase: forms double bond (FAD required).

  2. Enoyl-CoA hydratase: introduces hydroxyl group (H2O required).

  3. Hydroxyacyl-CoA dehydrogenase: produces ketone (NAD+ required).

  4. Thiolase: generates acetyl-CoA and a shortened acyl-CoA.

Page 24: Overview of Reaction Products

  • Fatty acyl-CoA → Acetyl CoA, FADH2, NADH, smaller fatty acyl-CoA.

  • Yields a stoichiometric relationship based on the initial carbon count (n).

Page 28: ATP Yield from Palmitate

  • Complete oxidation of palmitate produces:

    • Total: 106 ATP calculation from beta-oxidation and TCA cycle combined.

Page 30: Energy Comparison

  • Glucose yields ~38 ATP; palmitate yields 106 ATP.

  • Preference for glucose in cellular metabolism unless high fat intake.

Page 31: Ketogenesis

  • Fasting or starvation state increases liver's reliance on fatty acids for energy, feeding gluconeogenesis.

Page 32: Conversion to Ketone Bodies

  • Excess acetyl CoA converted to:

    • Acetoacetate, Beta-hydroxybutyrate, Acetone for energy in peripheral tissues.

Page 33: Characteristics of Ketones

  • Ketosis occurs during fat-heavy diets; distinct from ketoacidosis.

Page 37: Utilization of Ketone Bodies

  • Source of energy for the brain and muscles, primarily during starvation.

Page 39: Hormonal Regulation of Lipolysis

  • Glucagon, Epinephrine, Cortisol stimulate lipolysis under specific bodily conditions.