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Fat Metabolism — Rewritten Notes

Fat Metabolism

  • The word "lipid" is derived from the Greek word "lipos", which means fat.
  • Lipids are organic compounds made up from the esterification of fatty acids and alcohols.
    • Examples: triglycerides (80–90%), phospholipids, fatty acids, etc.
  • The formation and breakdown of lipids is known as lipid metabolism, which involves:
    • Lipogenesis — formation of lipids
    • Oxidation of fatty acids — to produce energy

Fatty Acids

  • Fatty acids are monocarboxylic acids with an aliphatic carbon chain, mainly obtained from the breakdown of lipids.
Saturated fatty acids — Fatty acids in which hydrocarbons and other functional groups are connected with single bonds.
Unsaturated fatty acids — They have one or more double-bonded functional groups in the carbon atom chain.

Metabolism of Fatty Acids

Fatty acids generally occur in the body as esters. These esters are hydrolysed by the enzyme esterase to form free fatty acids. These acids are then oxidized by enzymes to form CO₂ and water with the release of energy. The oxidation of fatty acids results in various compounds.

β-Oxidation of Fatty Acids

This is a process in which fatty acids are broken down to smaller units of Acyl-CoA, which is then used to produce energy through the citric acid (Krebs) cycle.
  • It occurs in the mitochondria.
  • It occurs in 3 stages:
    1. Activation of fatty acids in the cytosol
    2. Transport of activated fatty acids into mitochondria
    3. β-Oxidation in the mitochondrial matrix

Stage 1 — Activation of Fatty Acids in the Cytosol

Fatty acids are activated to Acyl-CoA in the presence of enzymes thiokinase and Acyl-CoA synthetase.
It is a two-step reaction:
  • Fatty acid + ATP → Acyladenylate
  • Acyladenylate + CoA → Acyl-CoA
Pathway: Fatty acid —(thiokinase)→ Acyladenylate —(PPi → 2Pi, pyrophosphatase)→ Acyl-CoA (ATP → AMP consumed)

Stage 2 — Transport of Activated Fatty Acids into Mitochondria

The inner mitochondrial membrane is impermeable to fatty acids. A specialized carnitine carrier system operates to transport activated fatty acids from the cytosol to the mitochondria. This occurs in 4 steps:
  1. The acyl group of Acyl-CoA is transferred to carnitine, catalyzed by Carnitine Acyl Transferase I (present on the outer surface of the inner mitochondrial membrane).
  2. The Acyl-carnitine is transported across the membrane to the mitochondrial matrix by a specific carrier protein.
  3. Carnitine Acyl Transferase II (present on the inner surface of the inner mitochondrial membrane) converts Acyl-carnitine back to Acyl-CoA.
  4. The carnitine released returns to the cytosol for reuse.
Diagram Summary:
CytosolMitochondrial Matrix
Acyl-CoA + Carnitine←Carnitine + Acyl-CoA
↓ Acyl Transferase I↑ Acyl Transferase II
CoASH releasedCoASH added
Acyl-Carnitine→Acyl-Carnitine

Stage 3 — β-Oxidation in the Mitochondrial Matrix

β-Oxidation comprises 4 reactions:
1. Oxidation: Acyl-CoA undergoes dehydrogenation by a FAD-dependent flavoenzyme, Acyl-CoA dehydrogenase. A double bond is formed between the α and β carbons.
2. Hydration: Enoyl-CoA hydratase brings about the hydration of the double bond to form β-hydroxyacyl-CoA.
3. Oxidation: β-Hydroxyacyl-CoA dehydrogenase catalyzes the second oxidation and generates NADH. The product formed is β-ketoacyl-CoA.
4. Cleavage (Thiolysis): The final reaction in β-oxidation is the liberation of a 2-carbon fragment, acetyl-CoA, from the acyl-CoA. This occurs by a thiolytic cleavage catalyzed by β-ketoacyl-CoA thiolase.
β-Oxidation Pathway:
Acyl-CoA ↓ (FAD → FADH₂) — Acyl-CoA dehydrogenase Trans-Enoyl-CoA ↓ (H₂O added) — Enoyl-CoA hydratase β-Hydroxyacyl-CoA ↓ (NAD⁺ → NADH + H⁺) — β-Hydroxyacyl-CoA dehydrogenase β-Ketoacyl-CoA ↓ (CoASH added) — Thiolase Acetyl-CoA → Krebs Cycle + Acyl-CoA (shortened by 2C, re-enters cycle)

Energy Yield from Oxidation of Palmitic Acid (16C)

The oxidation of palmitic acid (a commonly used example) generates:
  • 7 FADH₂, 7 NADH, and 8 Acetyl-CoA
StepATP Yield
β-Oxidation (7 cycles): 7 FADH₂ × 2 ATP14 ATP
β-Oxidation (7 cycles): 7 NADH × 3 ATP21 ATP
8 Acetyl-CoA via TCA cycle (× 12 ATP each)96 ATP
Energy used for activation−2 ATP
Total ATP yield129 ATP
Total ATP yield from oxidation of one molecule of palmitic acid = 129 ATP
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