UPSC MainsBOTANY-PAPER-II20235 Marks
Q28.

How do the three stages in fatty acid oxidation converge to conserve energy as ATP?

How to Approach

This question requires a detailed understanding of beta-oxidation, the process by which fatty acids are broken down to generate energy. The answer should focus on the three stages – activation, transport into mitochondria, and the beta-oxidation cycle itself – and explicitly link each stage to ATP production, either directly or indirectly through the generation of NADH and FADH2. A clear, step-by-step explanation is crucial, emphasizing the role of key enzymes and cofactors. The answer should demonstrate an understanding of the electron transport chain and oxidative phosphorylation as the ultimate ATP-generating processes.

Model Answer

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Introduction

Fatty acid oxidation is a catabolic process that breaks down fatty acids to generate acetyl-CoA, which then enters the citric acid cycle, ultimately leading to ATP production. This process is a major energy source, particularly during periods of fasting or prolonged exercise. The complete oxidation of a fatty acid involves three distinct stages: activation of the fatty acid, its transport into the mitochondrial matrix, and the cyclical process of beta-oxidation itself. Each stage is crucial for efficient energy conservation in the form of ATP, either directly or through the generation of reducing equivalents like NADH and FADH2.

Stage 1: Activation of Fatty Acids

The first stage involves activating fatty acids in the cytosol. Long-chain fatty acids are first activated by attaching them to Coenzyme A (CoA) to form fatty acyl-CoA. This reaction is catalyzed by acyl-CoA synthetase and requires ATP hydrolysis.

  • Reaction: Fatty acid + CoA + ATP → Fatty acyl-CoA + AMP + PPi
  • ATP Consumption: This stage directly consumes 1 ATP molecule per fatty acid activated.
  • Significance: Activation makes the fatty acid reactive for subsequent transport and oxidation.

Stage 2: Transport into the Mitochondria

Fatty acyl-CoA cannot directly cross the inner mitochondrial membrane. The carnitine shuttle system facilitates its transport. This involves three key steps:

  • Step 1: Fatty acyl-CoA reacts with carnitine, catalyzed by carnitine palmitoyltransferase I (CPT I), located on the outer mitochondrial membrane, forming fatty acyl-carnitine.
  • Step 2: Fatty acyl-carnitine is transported across the inner mitochondrial membrane by carnitine acylcarnitine translocase.
  • Step 3: Inside the mitochondrial matrix, carnitine palmitoyltransferase II (CPT II) regenerates fatty acyl-CoA and carnitine.

This stage doesn't directly produce ATP, but it's essential for accessing the enzymes required for beta-oxidation within the mitochondrial matrix.

Stage 3: Beta-Oxidation Cycle

This is the core process of fatty acid breakdown, occurring in the mitochondrial matrix. It’s a repetitive four-step cycle that shortens the fatty acyl-CoA by two carbon atoms with each turn, releasing acetyl-CoA.

  • Step 1: Oxidation: Fatty acyl-CoA is oxidized by acyl-CoA dehydrogenase, producing FADH2 and a trans-Δ2-enoyl-CoA.
  • Step 2: Hydration: Enoyl-CoA is hydrated by enoyl-CoA hydratase, forming L-β-hydroxyacyl-CoA.
  • Step 3: Oxidation: L-β-hydroxyacyl-CoA is oxidized by β-hydroxyacyl-CoA dehydrogenase, producing NADH and β-ketoacyl-CoA.
  • Step 4: Cleavage: β-ketoacyl-CoA is cleaved by thiolase, releasing acetyl-CoA and a shortened fatty acyl-CoA.

The cycle repeats until the fatty acid is completely broken down into acetyl-CoA molecules.

ATP Conservation from Beta-Oxidation Products

The energy conserved during fatty acid oxidation comes primarily from the reducing equivalents (NADH and FADH2) generated during beta-oxidation and the acetyl-CoA produced.

  • NADH: Each NADH molecule yields approximately 2.5 ATP molecules through oxidative phosphorylation in the electron transport chain.
  • FADH2: Each FADH2 molecule yields approximately 1.5 ATP molecules through oxidative phosphorylation.
  • Acetyl-CoA: Acetyl-CoA enters the citric acid cycle, generating more NADH, FADH2, and GTP (which is equivalent to ATP). Each acetyl-CoA yields approximately 10 ATP molecules when fully oxidized in the citric acid cycle and oxidative phosphorylation.

For example, the beta-oxidation of palmitic acid (a 16-carbon fatty acid) yields 8 acetyl-CoA molecules, 7 FADH2 molecules, and 7 NADH molecules. This translates to a significant ATP yield (approximately 106 ATP molecules) after accounting for the initial ATP investment in the activation stage.

Product ATP Yield per Molecule Total ATP (Palmitic Acid)
NADH 2.5 17.5
FADH2 1.5 10.5
Acetyl-CoA 10 80
ATP (Net) - 106 (approx.)

Conclusion

In conclusion, the three stages of fatty acid oxidation – activation, transport, and beta-oxidation – are intricately linked to conserve energy as ATP. While the activation stage consumes ATP, the subsequent stages generate reducing equivalents (NADH and FADH2) and acetyl-CoA, which ultimately fuel the electron transport chain and citric acid cycle, leading to substantial ATP production. This process highlights the efficiency of fatty acids as a concentrated energy source, crucial for sustaining cellular functions.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Beta-oxidation
The metabolic process by which fatty acids are broken down in the mitochondria to generate acetyl-CoA, NADH, and FADH2.
Acyl-CoA synthetase
An enzyme that catalyzes the activation of fatty acids by attaching them to Coenzyme A, using ATP as an energy source.

Key Statistics

Approximately 9 kcal of energy are released per gram of fat oxidized, compared to 4 kcal per gram of carbohydrate or protein (data as of 2023).

Source: Textbook of Biochemistry with Clinical Correlations, 8th Edition

Fatty acids contribute to approximately 60% of the body’s energy needs at rest (data as of 2022).

Source: Guyton and Hall Textbook of Medical Physiology, 14th Edition

Examples

Carnitine Deficiency

Carnitine deficiency, a genetic disorder, impairs the transport of fatty acids into the mitochondria, leading to reduced energy production and symptoms like muscle weakness and heart problems. This demonstrates the critical role of the carnitine shuttle in fatty acid oxidation.

Frequently Asked Questions

What happens to the acetyl-CoA produced from fatty acid oxidation?

Acetyl-CoA enters the citric acid cycle (Krebs cycle) where it is further oxidized to generate more NADH, FADH2, and GTP, ultimately leading to ATP production through oxidative phosphorylation.

Topics Covered

BiologyBiochemistryMetabolismCellular RespirationLipid Metabolism