Fatty acid synthesis is the metabolic process where organisms create fatty acids from precursor molecules. This is a fundamental pathway, serving as a primary method for long-term energy storage. The fatty acids produced are also structural components of cell membranes, which enclose every cell and its internal organelles. When the body has more energy than it needs for immediate use, it converts excess carbohydrates and proteins into fatty acids that are then stored as triglycerides.
Prerequisites for Synthesis
Fatty acid synthesis primarily takes place in the cytoplasm, the gel-like substance filling the cell. The main building block for this process is a two-carbon molecule called acetyl-CoA. However, most acetyl-CoA is generated inside the mitochondria through the breakdown of carbohydrates and fats. The inner mitochondrial membrane is impermeable to acetyl-CoA, preventing it from directly exiting to the cytoplasm where synthesis occurs.
To overcome this barrier, the cell uses a transport system known as the citrate shuttle. Inside the mitochondrion, acetyl-CoA combines with oxaloacetate to form citrate. A specific transporter protein then moves the newly formed citrate across the mitochondrial membrane and into the cytoplasm. Once there, the process is reversed by an enzyme called ATP-citrate lyase, which cleaves the citrate molecule to release the original acetyl-CoA and oxaloacetate, a reaction that requires energy from one ATP molecule.
The Initial and Committed Step
With acetyl-CoA present in the cytoplasm, the first chemical reaction of fatty acid synthesis can begin. This initial step is the point of no return for the pathway. Before the acetyl-CoA units can be linked together, they must be chemically activated by an enzyme named Acetyl-CoA Carboxylase, or ACC.
The reaction catalyzed by ACC converts acetyl-CoA into a three-carbon molecule called malonyl-CoA. This is achieved by adding a carboxyl group to acetyl-CoA, a reaction that requires both biotin and energy from an ATP molecule. This conversion is considered the “committed step” in fatty acid synthesis because once malonyl-CoA is formed, it is designated for creating fatty acids.
The Elongation Cycle
The core of fatty acid synthesis is a cyclical process that builds the fatty acid chain two carbons at a time, managed by a multi-enzyme complex called Fatty Acid Synthase (FAS). The process begins with an acetyl-CoA molecule priming the FAS complex, after which malonyl-CoA molecules serve as the source for all subsequent two-carbon additions. Each elongation cycle involves four distinct chemical reactions.
- Condensation: A malonyl-CoA molecule attaches to the growing chain, releasing one molecule of carbon dioxide. Only two of its three carbons are added.
- Reduction: A part of the growing chain is reduced using an electron donor molecule called NADPH.
- Dehydration: A molecule of water is removed to create a double bond.
- Reduction: A second reduction, also requiring NADPH, removes the double bond, resulting in a saturated carbon chain that is two carbons longer.
This four-step sequence repeats until the final fatty acid is formed, which for the primary product is seven times.
Final Product and Further Modifications
The elongation cycles continue until a 16-carbon fatty acid known as palmitate, the primary product of the Fatty Acid Synthase complex, is formed. The completed palmitate chain is then released from the FAS enzyme, concluding the main synthesis pathway.
Although palmitate is the principal fatty acid synthesized, it serves as a precursor for other types of fatty acids. Cells contain other enzymes, located in areas like the endoplasmic reticulum, that can further modify palmitate. These enzymes can perform elongation reactions to create fatty acids longer than 16 carbons. They can also introduce double bonds through desaturation, creating unsaturated fatty acids with different physical properties and biological roles.
Regulating the Synthesis Pathway
The rate of fatty acid synthesis is tightly controlled to match the cell’s energy needs. This regulation focuses on Acetyl-CoA Carboxylase (ACC), the enzyme that catalyzes the committed step of the pathway. The cell uses two main strategies to control ACC activity: allosteric regulation and hormonal signals.
Allosteric regulation provides rapid, local control. The ACC enzyme is activated by citrate; high levels signal that building blocks and energy are abundant. Conversely, the enzyme is inhibited by long-chain fatty acids, the final products of the pathway. This product inhibition ensures that synthesis shuts down when enough fatty acids have been produced.
Hormonal regulation adjusts fatty acid synthesis in response to the body’s overall energy status. After a meal, high blood glucose prompts the pancreas to release insulin, which activates ACC to promote fat storage. During fasting or stress, hormones like glucagon and epinephrine are released, which inhibit ACC to conserve energy and glucose.