Fatty Acid Metabolism

A fatty acid contains a long hydrocarbon chain and a terminal carboxylate group. Fatty acid metabolism consists of catabolic processes that generate energy and anabolic processes that create biologically important molecules. Fatty acids are a family of molecules classified within the lipid macronutrient class. One role of fatty acids in animal metabolism is energy production, captured in the form of adenosine triphosphate (ATP). It can contribute to the important needs of cancer cells: energy, growth, and membrane synthesis. When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO2 and water by beta-oxidation and the citric acid cycle. Furthermore, fatty acids are catabolized by fatty acid oxidation, which is an important source of nicotinamide adenine dinucleotide phosphate (NADPH).

Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants. Cancer cells require NADPH, which is used during fatty acid synthesis and oxidative stress inhibition. In addition, fatty acids are important components of the phospholipids that form the phospholipid bilayers out of which all the membranes of the cell are constructed (the plasma membrane and other membranes that enclose all the organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus). Fatty acid degradation and synthesis are relatively simple processes that are essentially the reverse of each other.

Fatty acid metabolism studies were restricted to SMA patients and no extensive characterization has been performed in preclinical models. Fatty acids can also be cleaved, or partially cleaved, from their chemical attachments in the cell membrane to form second messengers within the cell, and local hormones in the immediate vicinity of the cell. Disturbed fatty acid metabolism has been documented in patients with type 2 diabetes and lesser degrees of glucose intolerance. The prostaglandins made from arachidonic acid stored in the cell membrane, are probably the most well known group of these local hormones. Fatty acid synthesis is essentially the reverse of this process.