Fatty Acid Synthesis


Fatty acids are essential components of cell membranes, energy storage molecules, and signaling molecules in living organisms. Fatty acids can be obtained from dietary sources or synthesized endogenously by the cells. The process of synthesizing fatty acids from simple precursors such as sugars or amino acids is called de novo fatty acid synthesis.

De novo fatty acid synthesis occurs mainly in the cytosol of liver and adipose tissue cells, where a multienzyme complex called fatty acid synthase (FAS) catalyzes the sequential addition of two-carbon units to a growing fatty acyl chain. The main product of de novo fatty acid synthesis is palmitate, a 16-carbon saturated fatty acid, which can be further elongated or desaturated to produce other types of fatty acids.

De novo fatty acid synthesis is regulated by two key enzymes: acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). ACC converts acetyl-CoA to malonyl-CoA, which is the substrate for FAS. FAS then combines malonyl-CoA with acetyl-CoA to form a four-carbon unit, and repeats this cycle until palmitate is formed. Each cycle consumes one ATP and two NADPH molecules, which provide the energy and reducing power for the reactions.

De novo fatty acid synthesis is influenced by various hormonal and nutritional factors that modulate the activity and expression of ACC and FAS. For example, insulin stimulates fatty acid synthesis by activating ACC, while glucagon and epinephrine inhibit it by inactivating ACC. De novo fatty acid synthesis is also responsive to the availability of substrates and products. For instance, high levels of glucose or citrate increase fatty acid synthesis by providing more acetyl-CoA and NADPH, while high levels of fatty acids or malonyl-CoA decrease it by inhibiting ACC or FAS.

De novo fatty acid synthesis is important for maintaining cellular lipid homeostasis and fulfilling various physiological functions. Fatty acids synthesized de novo can be incorporated into phospholipids, triglycerides, cholesterol esters, or other lipid derivatives that are essential for membrane structure, energy storage, hormone production, and protein modification. De novo fatty acid synthesis is also involved in cell growth, differentiation, and signaling, as well as in metabolic diseases such as obesity, diabetes, and cancer.