Lipid Metabolism

M ost of the lipids found in the body fall into the categories of fatty acids and triacylglycerols; glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property: their relative insolublity in water. Fatty acids, which are stored as triacylglycerols, serve as fuels, providing the body with its major source of energy (Fig. VI.1). Glycerophospholipids and sphingolipids, which contain esterified fatty acids, are found in membranes and in blood lipoproteins at the interfaces between the lipid components of these structures and the surrounding water. These membrane lipids form hydrophobic barriers between subcellular compartments and between cellular constituents and the extracellular milieu. Polyunsaturated fatty acids containing 20 carbons form the eicosanoids, which regulate many cellular processes (Fig. VI.2). Cholesterol adds stability to the phospholipid bilayer of membranes. It serves as the precursor of the bile salts, detergent-like compounds that function in the process of lipid digestion and absorption (Fig. VI.3). Cholesterol also serves as the precursor of the steroid hormones, which have many actions, including the regulation of metabolism, growth, and reproduction. The fat-soluble vitamins are lipids that are involved in such varied functions as vision, growth, and differentiation (vitamin A), blood clotting (vitamin K), prevention of oxidative damage to cells (vitamin E), and calcium metabolism (vitamin D). Triacylglycerols, the major dietary lipids, are digested in the lumen of the intestine (Fig. VI.4). The initial digestive products, free fatty acids and 2-monoacylglycerol, are reconverted to triacylglycerols in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons (so they can safely enter the circulation), and secreted into the lymph. Ultimately, chylomicrons enter the blood, serving as one of the major blood lipoproteins. Very low density lipoprotein (VLDL) is produced in the liver, mainly from dietary carbohydrate. Lipogenesis is an insulin-stimulated process through which glucose is converted to fatty acids, which are subsequently esterified to glycerol to form the triacylglycerols that are packaged in VLDL and secreted from the liver. Thus, chylomicrons primarily transport dietary lipids, and VLDL transports endogenously synthesized lipids. The triacylglycerols of chylomicrons and VLDL are digested by lipoprotein lipase (LPL), an enzyme found attached to capillary endothelial cells (see Fig. VI.4). The fatty acids that are released are taken up by muscle and many other tissues and oxidized to CO2 and water to produce energy (see Chapter 23). After a meal, these fatty acids are taken up by adipose tissue and stored as triacylglycerols. LPL converts chylomicrons to chylomicron remnants and VLDL to intermediate density lipoprotein (IDL). These products, which have a relatively low triacylglycerol content, are taken up by the liver by the process of endocytosis and degraded by lysosomal action. IDL may also be converted to low density lipoprotein (LDL) by further digestion of triacylglycerol. Endocytosis of LDL occurs in peripheral tissues as well as the liver (Table VI.1), and is the major means of cholesterol transport and delivery to peripheral tissues. 579 SECTION SIX