Fatty acid elongation in biosynthesis is the process of lengthening an existing fatty acid chain by adding two-carbon units. This occurs through a cyclical series of reactions.
The Process of Fatty Acid Elongation
Fatty acid elongation primarily occurs in the endoplasmic reticulum (ER) and mitochondria, utilizing different enzyme systems and substrates than fatty acid synthesis (which primarily occurs in the cytoplasm). The elongation process involves the following key steps, repeated iteratively to add two carbons at a time:
- Condensation: An acyl group (derived from acyl-ACP or acyl-CoA) condenses with malonyl-CoA (or malonyl-ACP in bacteria) to form a β-ketoacyl intermediate. This reaction is catalyzed by β-ketoacyl-CoA synthase (or condensing enzyme).
- Reduction: The β-ketoacyl intermediate is reduced by β-ketoacyl reductase to a β-hydroxyacyl intermediate. NADPH is typically the reducing agent.
- Dehydration: The β-hydroxyacyl intermediate is dehydrated by β-hydroxyacyl dehydratase to form a trans-Δ2-enoyl intermediate.
- Reduction: The trans-Δ2-enoyl intermediate is reduced by enoyl reductase to form a saturated acyl-CoA that is two carbons longer than the starting acyl group. NADPH is typically the reducing agent.
These four steps are repeated until the desired fatty acid length is achieved.
Key Enzymes and Substrates
- β-ketoacyl-CoA synthase (condensing enzyme): Catalyzes the condensation reaction. Different isoforms exist to elongate fatty acids of different lengths.
- Malonyl-CoA: Provides the two-carbon units for elongation.
- NADPH: Serves as the reducing agent in the reduction steps.
Location of Fatty Acid Elongation
- Endoplasmic Reticulum (ER): The major site of fatty acid elongation in eukaryotes. Enzymes here primarily elongate fatty acids using malonyl-CoA. The ELOVL (elongation of very long chain fatty acids) enzymes play a crucial role in this process.
- Mitochondria: Also involved in fatty acid elongation.
Significance of Fatty Acid Elongation
Fatty acid elongation is critical for:
- Producing fatty acids of varying lengths: Different cell types and tissues require fatty acids of specific lengths for their structure and function.
- Synthesis of specialized lipids: Very long-chain fatty acids are essential components of sphingolipids and other specialized lipids.
- Regulation of membrane fluidity: Fatty acid composition, including chain length, influences membrane fluidity and function.
