Fatty acids (see Chapter 2) play a number of important roles in cells. In addition to being a cellular fuel source (see the discussion of aerobic oxidation in Chapter 12), fatty acids are key components of both the phospholipids and the sphingolipids that make up cellular membranes; they also anchor some proteins to cellular membranes (see Figure 7-19). Thus the regulation of fatty acid synthesis plays a key role in the regulation of membrane synthesis as a whole. The major fatty acids in phospholipids contain 14, 16, 18, or 20 carbon atoms and include both saturated and unsaturated chains. The fatty acyl chains found on sphingolipids can be longer than those in the phosphoglycerides, containing up to 26 carbon atoms, and may bear other chemical modifications (e.g., hydroxylation) as well.

Fatty acids are synthesized from the two-carbon building block acetate (CH₃COO⁻). In cells, both acetate and the intermediates in fatty acid biosynthesis are esterified to a large water-soluble molecule called coenzyme A (CoA), as exemplified by the structure of acetyl CoA (below).

Acetyl CoA is an important intermediate in the metabolism of glucose, fatty acids, and many amino acids, as detailed in Chapter 12. It also contributes acetyl groups in many biosynthetic pathways. Saturated fatty acids (with no carbon-carbon double bonds) containing 14 or 16 carbon atoms are made from acetyl CoA by two enzymes, acetyl-CoA carboxylase and fatty acid synthase. In animal cells, these enzymes are found in the cytosol; in plants, they are found in chloroplasts. Palmitoyl CoA (a 16-carbon fatty acyl group linked to CoA) can be elongated to 18–24 carbons by the sequential addition of two-carbon units in the endoplasmic reticulum (ER) or sometimes in the mitochondrion. Desaturase enzymes, also located in the ER, introduce double bonds at specific positions in some fatty acids, yielding unsaturated fatty acids. Oleyl CoA (oleate linked to CoA; see Table 2-4), for example, is formed by removal of two H atoms from stearyl CoA. In contrast to free fatty acids, fatty acyl CoA derivatives are soluble in aqueous solutions because of the hydrophilicity of the CoA segment.