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In this section, we consider some of the special challenges that a cell faces in synthesizing and transporting lipids, which are poorly soluble in the aqueous interior of a cell. The focus of our discussion will be the biosynthesis and movement of the major lipids found in cellular membranes—phospholipids, sphingolipids, and cholesterol—and their precursors. In lipid biosynthesis, water-soluble precursors are assembled into membrane-associated intermediates that are then converted into membrane lipid products. The movement of these lipids, especially membrane components, between different organelles is critical for maintaining the proper composition and properties of membranes and overall cell structure.

A fundamental principle of membrane biosynthesis is that cells synthesize new membranes only by the expansion of existing membranes. [The one exception may be autophagy, in which new membrane is formed first through the formation of an autophagic crescent, the construction of which involves modification of phosphatidylethanolamine with the ubiquitin-like modifier Atg8 (see Figure 14-35).] Although some early steps in the synthesis of membrane lipids take place in the cytosol, the final steps are catalyzed by enzymes bound to preexisting cellular membranes, and the products are incorporated into the membranes as they are generated. Evidence for this process is seen when cells are briefly exposed to radioactively labeled precursors (e.g., phosphates or fatty acids): all the phospholipids and sphingolipids incorporating these labeled precursors are associated with intracellular membranes; as expected from the hydrophobicity of the fatty acyl chains, none are found free in the cytosol.

After they are formed, membrane lipids must be distributed appropriately both between the leaflets of a given membrane and among the independent membranes of different organelles in eukaryotic cells, as well as the plasma membrane. Here we consider how this precise lipid distribution is accomplished; in Chapters 13 and 14, we discuss how membrane proteins are inserted into cellular membranes and trafficked to their appropriate location within the cell.