Fatty acid synthase

Fatty acid synthase (FAS) is a multi-enzyme protein that catalyzes the synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA, in the presence of NADPH. This process, known as fatty acid synthesis, is crucial for the production of fatty acids, which are key components of cell membranes, signaling molecules, and energy storage molecules. Fatty acid synthase plays a vital role in lipid metabolism and is found in both prokaryotic and eukaryotic organisms, although its structure and mechanism of action vary significantly between these groups.

Structure and Function

Fatty acid synthase in eukaryotes is a large, multi-functional enzyme complex. It operates as a dimer, with each monomer containing all the enzymatic activities required for the sequential reactions of fatty acid synthesis. These reactions include the condensation of acetyl-CoA and malonyl-CoA, reduction, dehydration, and a second reduction, leading to the elongation of the fatty acid chain by two carbon atoms. The process repeats until a long-chain fatty acid, typically 16 or 18 carbons in length, is produced.

In prokaryotes, the enzymes involved in fatty acid synthesis are separate, discrete proteins that work in a coordinated fashion. This difference in organization between prokaryotes and eukaryotes reflects the evolutionary divergence in the mechanisms of fatty acid synthesis.

Regulation

The activity of fatty acid synthase is tightly regulated by nutritional and hormonal signals. Insulin, for example, upregulates FAS expression, promoting fatty acid synthesis in times of energy abundance. Conversely, glucagon and epinephrine downregulate FAS, reducing fatty acid synthesis during energy scarcity. Additionally, the product of the FAS reaction, palmitate, can inhibit the enzyme's activity through feedback inhibition, thus preventing overproduction of fatty acids.

Clinical Significance

Alterations in fatty acid synthase activity have been implicated in several metabolic diseases, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). FAS is also overexpressed in many cancers, making it a potential target for anticancer therapies. Inhibitors of fatty acid synthase are currently being explored as therapeutic agents in metabolic diseases and cancer.

Research Directions

Research on fatty acid synthase continues to focus on understanding its structure, regulation, and role in disease. Efforts are also underway to develop specific inhibitors of FAS as potential drugs for treating cancer and metabolic disorders.