Oxidation of Fatty Acids With an Odd Number of Carbon Atoms
1. Overview
- Fatty acids that have odd number of carbons undergo β-oxidation just like even-numbered fatty acids until the final step.
- The main difference is in the last cleavage product.
- Instead of producing only acetyl-CoA, the final step produces:
- 1 Acetyl-CoA
- 1 Propionyl-CoA (3-carbon compound)
2. Breakdown Steps
- β-oxidation proceeds normally, removing 2-carbon units and generating:
- Acetyl-CoA
- NADH
- FADH₂
- When 3 carbons remain, the product formed is:
- Propionyl-CoA
3. Metabolism of Propionyl-CoA (The Key Difference)
Propionyl-CoA cannot directly enter the citric acid cycle. It must be converted into Succinyl-CoA.
The Conversion Requires 3 Enzymes:
- Propionyl-CoA Carboxylase
- Converts Propionyl-CoA → Methylmalonyl-CoA
- Requires Biotin (Vitamin B₇).
- Methylmalonyl-CoA Racemase
- Converts D-form → L-form of Methylmalonyl-CoA.
- Methylmalonyl-CoA Mutase
- Converts L-Methylmalonyl-CoA → Succinyl-CoA
- Requires Vitamin B₁₂ (Cobalamin).
Importance of Vitamin B₁₂
- Vitamin B₁₂ is essential for the conversion of methylmalonyl-CoA to succinyl-CoA.
- Deficiency leads to accumulation of Methylmalonic acid → Methylmalonic acidemia / aciduria.
- This accumulation causes:
- Neurological symptoms (due to abnormal myelin formation)
- Metabolic acidosis.
4. Fate of Succinyl-CoA
- Succinyl-CoA enters the Citric Acid Cycle.
- It can be converted to:
- Malate → Oxaloacetate → Glucose (via gluconeogenesis).
- → This explains why odd-chain fatty acids are slightly glucogenic, unlike even-chain fatty acids.