Fatty acids are manufactured through a process called de novo lipogenesis, primarily in the cytosol of cells, starting with acetyl-CoA. This process relies on several key enzymes.
De Novo Lipogenesis: A Detailed Look
De novo lipogenesis describes the synthesis of fatty acids from acetyl-CoA. This pathway is particularly active in the liver of rodents and humans. The process relies on a few key enzymes.
Key Enzymes Involved
| Enzyme | Role | Location |
|---|---|---|
| ATP citrate lyase | Converts citrate to acetyl-CoA in the cytosol | Cytosol |
| Acetyl-CoA carboxylase | Carboxylates acetyl-CoA to form malonyl-CoA (a committed step) | Cytosol |
| Fatty acid synthase (FAS) | Catalyzes the repetitive addition of two-carbon units (from malonyl-CoA) to a growing fatty acyl chain | Cytosol |
Steps in Fatty Acid Synthesis
- Acetyl-CoA Production: Acetyl-CoA, the starting material, is generated in the mitochondria. Because the mitochondrial membrane is impermeable to acetyl-CoA, it is shuttled to the cytosol in the form of citrate. ATP citrate lyase then cleaves citrate to regenerate acetyl-CoA in the cytosol, according to the reference: fatty acids can be synthesized from acetyl-CoA in the cytosol through reactions catalyzed by ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase.
- Activation of Acetyl-CoA: Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA. This is a crucial regulatory step.
- Chain Elongation: Fatty acid synthase (FAS) is a large multi-enzyme complex that catalyzes the repetitive addition of two-carbon units from malonyl-CoA to a growing fatty acyl chain. This process involves a series of reduction, dehydration, and condensation reactions. The process continues until palmitic acid (a 16-carbon fatty acid) is formed.
- Further Modification: Palmitic acid can then be further elongated or desaturated by other enzymes to produce a variety of other fatty acids.
Tissue Location
According to the reference: In rodents and humans, the highest fatty acid synthesis activity is found in the liver.
- Liver: The primary site for fatty acid synthesis.
- Adipose Tissue: Fatty acids are synthesized here for storage as triglycerides.
- Lactating mammary glands: Synthesize fatty acids for milk production.
