Membrane lipids sphingolipids, synthesis

After synthesis on the smooth ER, the polar lipids, including the glycerophospholipids, sphingolipids, and glycolipids, are inserted into specific cellular membranes in specific proportions, by mechanisms not yet understood. Membrane lipids are insoluble in water, so they cannot simply diffuse from their point of synthesis (the ER) to their point of insertion. Instead, they are delivered in membrane vesicles that bud from the Golgi complex then move to and fuse with the target membrane (see Fig. 11-23). Cytosolic proteins also bind phospholipids and sterols and transport them between cellular membranes. These mechanisms contribute to the establishment of the characteristic lipid compositions of organelle membranes (see Fig. 11-2). 

The polar lipids of membranes undergo constant metabolic turnover, the rate of their synthesis normally counterbalanced by the rate of breakdown. The breakdown of lipids is promoted by hydrolytic enzymes in lysosomes, each enzyme capable of hydrolyzing a specific bond. When sphingolipid degradation is impaired by a defect in one of these enzymes (Fig. 1), partial breakdown products accumulate in the tissues, causing serious disease. 

Lipids have several important functions in animal cells, which include serving as structural components of membranes and as a stored source of metabolic fuel (Griner et al., 1993). Eukaryotic cell membranes are composed of a complex array of proteins, phospholipids, sphingolipids, and cholesterol. The relative proportions and fatty acid composition of these components dictate the physical properties of membranes, such as fluidity, surface potential, microdomain structure, and permeability. This in turn regulates the localization and activity of membrane-associated proteins. Assembly of membranes necessitates the coordinate synthesis and catabolism of phospholipids, sterols, and sphingolipids to create the unique properties of a given cellular membrane. This must be an extremely complex process that requires coordination of multiple biosynthetic and degradative enzymes and lipid transport activities. 

A cell cannot divide or enlarge unless it makes sufficient amounts of additional membranes to accommodate the expanded area of its outer surface and internal organelles. Thus the generation of new cell membranes is as fundamentally important to the life of a cell as is protein synthesis or DNA replication. Although the protein components of biomembranes are critical to their biological functions, the basic structural and physical properties of membranes are determined by their lipid components—principally phospholipids, sphingolipids, and sterols such as cholesterol (Table 18-1). Cells must be able to synthesize or import these molecules to form membranes. 

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