Fatty Acid Oxidation Notes

Lecture Overview

  • Topic: Fatty Acid Oxidation (Lecture #28)
  • Course: BCHE 3200 - Principles of Biochemistry

Fatty Acid Oxidation

  • Definition: Process of breaking down fatty acids into Acetyl CoA, producing ketones and other metabolic fuels.
  • Energy Source: Major energy supply for the liver.
  • Process: Leads to the formation of ketone bodies in the liver available for the brain and muscle.

Beta-Oxidation

  • Description: Key metabolic route for the breakdown of long-chain fatty acids.
  • Mechanism: Involves oxidation of the beta carbon (the second carbon) in the fatty acid chain, resulting in the release of a 2-carbon unit as acetyl-CoA.

Importance of Beta-Oxidation

  • Structure: Each fatty acid has a carboxyl group, a long chain of carbon (C) and hydrogen (H), and a carbonyl carbon.
  • Name: Named for the cleavage occurring between the alpha (𝛼) and beta (β) carbons of the fatty acid chain.

Location of Fatty Acid Oxidation

  • Key Sites:
    • Mitochondria
    • Peroxisomes
Fatty Acid Size and Location
  • Short/Medium Chain (2 – 12 carbons): Diffuse freely into mitochondria.
  • Long Chain (14 – 20 carbons): Require carnitine for transport into mitochondria.
  • Very Long Chain (>20 carbons): Must be oxidized in peroxisomes.

Overview of Fatty Acid Breakdown

  • Source: Adipose tissue contains triglycerides, which are composed of fatty acids.
  • Distribution: Fatty acids are sent to cells capable of metabolizing them.
  • Cell Types: Red blood cells and brain cannot metabolize fatty acids due to lack of mitochondria.

Steps in Fatty Acid Transport and Oxidation

A. Transport from Adipose Tissue
  • Lipases: Enzymes secreted by the pancreas convert triacylglycerols into fatty acids and glycerol.
B. Entry to Cytoplasm and Mitochondria
  • Formation of Acyl CoA: Fatty acids are activated by forming fatty acyl-CoA using fatty acyl-CoA synthetase.
    • Energy Investment: Requires 2 ATP (converted to AMP and PPi).
  • Transport Mechanism: Activated fatty acid (Fatty Acyl-CoA) is transferred to carnitine for mitochondrial transport through carnitine acyltransferases.
    • Transport in Mitochondria: Acyl carnitine is transported into the mitochondrial matrix by a translocase. Carnitine acyltransferase II then transfers the fatty acid back to CoA.
C. Oxidation in Mitochondrial Matrix
  • Process: Involves four steps:
    1. Dehydrogenation: Removal of H from 𝛼 and β carbons, forming a double bond, reducing FAD to FADH2.
    2. Hydration: Water is added, introducing OH at the β carbon and H at the α carbon.
    3. Dehydrogenation: Again, H is removed from the β carbon, reducing NAD to NADH.
    4. Thiolysis: Cleavage reaction using CoA that produces a new fatty acid and acetyl CoA.
Total ATP Yield from Palmitate Oxidation
  • Complete Oxidation of C16 Palmitoyl CoA: 7 cycles
    • Yield: 106 - 126 molecules of ATP.
    • Breakdown:
    • $(8 ext{ acetyl-CoA} imes 12.5 ext{ ATP/acetyl-CoA} = 100 ext{ ATP})$
    • $(7 ext{ FADH2} imes 1.5 ext{ ATP/FADH2} = 10.5 ext{ ATP})$
    • $(7 ext{ NADH} imes 2.5 ext{ ATP/NADH} = 17.5 ext{ ATP})$
    • Total ATP: $100 + 10.5 + 17.5 = 128 ext{ ATP}$.
  • Net ATP: $128 - 2 = 126 ext{ ATP}$ (subtracting activation costs).
Odd-Chain Fatty Acid Oxidation
  • Production: Yields propionyl CoA at the end of oxidation.
  • Conversion: Propionyl CoA is converted to succinyl-CoA and enters the citric acid cycle.
  • Coenzyme: Vitamin B12 is crucial for the conversion process.

Utilization of Fatty Acids as Fuel

  • Tissue Types: Fatty acid oxidation occurs in liver cells, fat cells, and other metabolizing tissues.
  • Byproducts: Acetyl CoA enters the citric acid cycle, producing CO2 and H2O as final products.
  • Broader Metabolism: Participates in various metabolic pathways including glycolysis, citric acid cycle, and lipid metabolism.