Fatty acid synthesis is the creation of fatty acids from smaller molecules. This process, also known as de novo lipogenesis, primarily occurs in the liver and fat cells (adipocytes) of mammals.
The Process of Fatty Acid Synthesis
The synthesis of fatty acids starts with acetyl-CoA and requires the reducing power of NADPH. Several key enzymes are involved:
-
ATP Citrate Lyase: This enzyme converts citrate (from the citric acid cycle) into acetyl-CoA and oxaloacetate, making acetyl-CoA available in the cytosol where fatty acid synthesis takes place.
-
Acetyl-CoA Carboxylase (ACC): This enzyme is a crucial rate-limiting step. It adds a carboxyl group to acetyl-CoA, converting it to malonyl-CoA. This reaction requires biotin and ATP.
-
Fatty Acid Synthase (FAS): This multi-enzyme complex carries out the cyclical reactions that elongate the fatty acid chain. Each cycle adds a two-carbon unit (from malonyl-CoA) to the growing fatty acid chain. This process involves repeated reduction, dehydration, and reduction steps, all requiring NADPH.
The process results in the creation of saturated fatty acids. Unsaturated fatty acids are formed later via the action of enzymes called desaturases, which introduce cis double bonds into the fatty acid chain.
Location and Regulation
In humans and rodents, the liver is the primary site for fatty acid synthesis. The process is tightly regulated, influenced by factors like insulin levels, dietary intake, and energy status of the cell. For example, high glucose levels increase fatty acid synthesis, while low energy states inhibit it.
Examples and Practical Insights
- High carbohydrate diets: Lead to increased fatty acid synthesis due to increased acetyl-CoA availability.
- Diabetes: Characterized by impaired regulation of fatty acid synthesis, contributing to elevated triglyceride levels.
- Therapeutic targets: Enzymes involved in fatty acid synthesis, like ACC, are potential targets for drugs aimed at treating metabolic disorders.
The synthesis of fatty acids requires reduced NADP+ as a cofactor, consuming two molecules of NADPH + H+ for each two-carbon unit added to the growing fatty acid chain. Fatty acids are synthesized in their saturated form, with desaturation occurring as a later step.
