Harper's Biochemistry - Lipid Transport & Storage Chapter 25 PDF

C H A P T E R Lipid Transport & Storage Kathleen M. Botham, PhD, DSc, & Peter A. Mayes, PhD, DSc O B J E C TI V E S 25...

C H A P T E R Lipid Transport & Storage Kathleen M. Botham, PhD, DSc, & Peter A. Mayes, PhD, DSc O B J E C TI V E S 25 Identify the four major groups of plasma lipoproteins and the four major lipid classes they carry. After studying this chapter, Illustrate the structure of a lipoprotein particle. you should be able to: Indicate the major types of apolipoprotein found in the different lipoprotein classes. Explain that triacylglycerol from the diet is carried to the liver in chylomicrons and from the liver to extrahepatic tissues in very-low-density lipoprotein (VLDL), and that these particles are synthesized in intestinal and liver cells, respectively, by similar processes. Illustrate the processes by which chylomicrons are metabolized by lipases to form chylomicron remnants, which are then removed from the circulation by the liver. Explain how VLDL is metabolized by lipases to intermediate-density lipoprotein (IDL) which may be cleared by the liver or converted to low-density lipoprotein (LDL), which functions to deliver cholesterol from the liver to extrahepatic tissues via the LDL (apoB100, E) receptor. Explain how high-density lipoprotein (HDL) is synthesized, indicate the mechanisms by which it accepts cholesterol from extrahepatic tissues and returns it to the liver in reverse cholesterol transport. Describe how the liver plays a central role in lipid transport and metabolism and how hepatic VLDL secretion is regulated by the diet and hormones. Indicate the roles of LDL and HDL in promoting and retarding, respectively, the development of atherosclerosis. Indicate the causes of alcoholic and nonalcoholic fatty liver disease (NAFLD). Explain the processes by which fatty acids are released from triacylglycerol stored in adipose tissue. Understand the role of brown adipose tissue in the generation of body heat. BIOMEDICAL IMPORTANCE cycle, followed by a period of negative caloric balance when the organism draws on its carbohydrate and fat stores. Lipo- Fat absorbed from the diet and lipids synthesized by the liver proteins mediate this cycle by transporting lipids from the and adipose tissue must be transported between the various intestines as chylomicrons—and from the liver as very- tissues and organs for utilization and storage. Since lipids are low-density lipoproteins (VLDL)—to most tissues for oxida- insoluble in water, the problem of how to transport them in tion and to adipose tissue for storage. Lipid is mobilized from the aqueous blood plasma is solved by associating nonpolar adipose tissue as free fatty acids (FFAs) bound to serum albu- lipids (triacylglycerol and cholesteryl esters) with amphipathic min. Abnormalities of lipoprotein metabolism cause various lipids (phospholipids and cholesterol) and proteins to make hypo- or hyperlipoproteinemias. The most common of these water-miscible lipoproteins. is in diabetes mellitus, where insulin deficiency causes exces- In a meal-eating omnivore such as the human, excess sive mobilization of FFA and underutilization of chylomicrons calories are ingested in the anabolic phase of the feeding and VLDL, leading to hypertriacylglycerolemia. Most other 247 248 SECTION V Metabolism of Lipids pathologic conditions affecting lipid transport are due primarily to These are (1) chylomicrons, derived from intestinal absorption inherited defects, some of which cause hypercholesterolemia of triacylglycerol and other lipids; (2) VLDL, derived from the and premature atherosclerosis (see Table 26–1). Obesity— liver for the export of triacylglycerol; (3) low-density lipo- particularly abdominal obesity—is a risk factor for increased proteins (LDL), responsible for the transport of cholesterol mortality, hypertension, Type 2 diabetes mellitus, hyperlipid- in humans and representing a final stage in the catabolism of emia, hyperglycemia, and various endocrine dysfunctions. VLDL; and (4) high-density lipoproteins, (HDL), involved in reverse cholesterol transport (see later and Chapter 26) and also in VLDL and chylomicron metabolism. Triacylglycerol LIPIDS ARE TRANSPORTED IN is the predominant lipid in chylomicrons and VLDL, whereas THE PLASMA AS LIPOPROTEINS cholesterol and phospholipid are the predominant lipids in LDL and HDL, respectively (see Table 25–1). Lipoproteins may Four Major Lipid Classes Are Present also be classified according to their electrophoretic properties in Lipoproteins into α- (HDL), β- (LDL), and pre-β (VLDL)-lipoproteins. Plasma lipids consist of triacylglycerols (16%), phospholipids (30%), cholesterol (14%), and cholesteryl esters (36%) and Lipoproteins Consist of a Nonpolar a much smaller fraction of unesterified long-chain fatty acids Core & a Single Surface Layer of (or FFAs) (4%). This latter fraction, the FFA, is metabolically the most active of the plasma lipids. Amphipathic Lipids The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface Four Major Groups of Plasma layer of amphipathic phospholipid and cholesterol molecules Lipoproteins Have Been Identified (Figure 25–1). These are oriented so that their polar groups Since fat is less dense than water, the density of a lipopro- face outward to the aqueous medium, as in the cell membrane tein decreases as the proportion of lipid to protein increases (see Chapters 21 and 40). The protein moiety of a lipoprotein (Table 25–1). Four major groups of lipoproteins have been iden- is known as an apolipoprotein or apoprotein, constituting tified that are important physiologically and in clinical diagnosis. nearly 70% of some HDL and as little as 1% of chylomicrons. TABLE 25–1 Composition of the Lipoproteins in Plasma of Humans Composition Diameter Density Protein Lipid Main Lipid Lipoprotein Source (nm) (g/Ml) (%) (%) Components Apolipoproteins Chylomicrons Intestine 90-1000