Metabolism And Movement Of Lipids

Fluorescence micrograph of hamster intestinal epithelium after cellular uptake into lipid droplets of an orally administered fluorescent analog of cholesterol (fluoresterol, dissolved in corn oil) from the intestinal lumen (upper left, unstained). [C. P. Sparrow et al., 1999, J. Lipid Res. 40:1747-1757.]

In this chapter we consider some of the special challenges that a cell faces in metabolizing and transporting lipids, which are poorly soluble in the aqueous interior of cells and in extracellular fluids. Cells use lipids for storing energy, building membranes, signaling within and between cells, sensing the environment, covalently modifying proteins, forming specialized permeability barriers (e.g., in skin), and protecting cells from highly reactive chemicals. Fatty acids, which are oxidized in mitochondria to release energy for cellular functions (Chapter 8), are stored and transported primarily in the form of triglycerides. Fatty acids are also precursors of phospholipids, the structural backbone of cellular membranes (Chapter 5). Cholesterol, another important membrane component, is a precursor for steroid hormones and other biologically active lipids that function in cell-cell signaling. Also derived from precursors of cholesterol biosynthesis are the fat-soluble vitamins, which have diverse functions including the detection of light by the retinal form of vitamin A in rhodopsin, the control of calcium metabolism by the active hormone form of vitamin D, protection against oxidative damage to cells by vitamin E, and the cofactor activity of vitamin K in the formation of blood clots.

With the exception of a few specialized cells that store large quantities of lipids, the overwhelming majority of lipids within cells are components of cellular membranes. Therefore we focus our discussion of lipid biosynthesis and movement on the major lipids found in cellular membranes and their precursors (Figure 18-1). In lipid biosynthesis, water-

soluble precursors are assembled into membrane-associated intermediates that are then converted into membrane lipid products. The movement of lipids, especially membrane components, between different organelles is critical for maintaining the proper composition and properties of membranes and overall cell structure, but our understanding of such in-tracellular lipid transport is still rudimentary. In contrast, analysis of the transport of lipids into, out of, and between cells is far more advanced, and we describe in some detail these lipid movements mediated by various cell-surface transport proteins and receptors.

We conclude the chapter by examining the connection between cellular cholesterol metabolism and atherosclerosis, which can lead to cardiovascular disease (e.g., heart attack,

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