Key Concepts of Section 7.3

Phospholipids, Sphingolipids, and Cholesterol: Synthesis and Intracellular Movement

• Saturated and unsaturated fatty acids of various chain lengths are components of phospholipids and sphingolipids.

• Fatty acids are synthesized from acetyl CoA by water-soluble enzymes and modified by elongation and desaturation in the endoplasmic reticulum (ER).

• Free fatty acids are transported within cells by fatty acid–binding proteins (FABPs).

• Fatty acids are incorporated into phospholipids through a multistep process. The final steps in the synthesis of phosphoglycerides and sphingolipids are catalyzed by membrane-associated enzymes primarily on the cytosolic face of the ER (see Figure 7-25).

• Each type of newly synthesized lipid is incorporated into the preexisting membranes on which it is made; thus, membranes are themselves the platform for the synthesis of new membrane material.

• Most membrane phospholipids are preferentially distributed in either the exoplasmic or the cytosolic leaflet. This asymmetry results in part from the action of flippases, which flip phospholipids from one leaflet to the other.

• The initial steps in cholesterol biosynthesis take place in the cytosol, whereas the last steps are catalyzed by enzymes associated with the ER membrane.

• The rate-controlling step in cholesterol biosynthesis is catalyzed by HMG-CoA reductase, whose transmembrane segments are embedded in the ER membrane and contain a sterol-sensing domain.

• Considerable evidence indicates that vesicular transport, direct protein-mediated contacts between different membranes, soluble lipid-transfer proteins, or all three may account for some inter-organelle transport of cholesterol and phospholipids (see Figure 7-27).