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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Appreciate the importance of cholesterol as an essential structural component of cell membranes and as a precursor of all other steroids in the body, and indicate its pathological role in cholesterol gallstone disease and atherosclerosis development.

  • Identify the five stages in the biosynthesis of cholesterol from acetyl-CoA.

  • Understand the role of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) in controlling the rate of cholesterol synthesis and explain the mechanisms by which its activity is regulated.

  • Appreciate that cholesterol balance in cells is tightly regulated and indicate the factors involved in maintaining the correct balance.

  • Explain the role of plasma lipoproteins, including chylomicrons, very low density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), in the transport of cholesterol between tissues in the plasma.

  • Name the two main primary bile acids found in mammals, outline the pathways by which they are synthesized from cholesterol in the liver, and understand the role of cholesterol 7α-hydroxylase in regulating the process.

  • Appreciate the importance of bile acid synthesis not only in the digestion and absorption of fats but also as a major excretory route for cholesterol.

  • Indicate how secondary bile acids are produced from primary bile acids by intestinal bacteria.

  • Explain what is meant by the “enterohepatic circulation” and why it is important.

  • Identify the lifestyle factors that influence plasma cholesterol concentrations and thus affect the risk of coronary heart disease.

  • Understand that the class of lipoprotein in which cholesterol is carried is important in determining the effects of plasma cholesterol on atherosclerosis development, with high levels of VLDL or LDL being deleterious and high levels of HDL being beneficial.

  • Give examples of inherited and noninherited conditions affecting lipoprotein metabolism that cause hypo- or hyperlipoproteinemia.

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BIOMEDICAL IMPORTANCE

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Cholesterol is present in tissues and in plasma either as free cholesterol or combined with a long-chain fatty acid as cholesteryl ester, the storage form. In plasma, both forms are transported in lipoproteins (see Chapter 25). Cholesterol is an amphipathic lipid and as such is an essential structural component of membranes, where it is important for the maintenance of the correct permeability and fluidity, and of the outer layer of plasma lipoproteins. It is synthesized in many tissues from acetyl-CoA and is the precursor of all other steroids in the body, including corticosteroids, sex hormones, bile acids, and vitamin D. As a typical product of animal metabolism, cholesterol occurs in foods of animal origin such as egg yolk, meat, liver, and brain. Plasma low-density lipoprotein (LDL) is the vehicle that supplies cholesterol and cholesteryl ester to many tissues. Free cholesterol is removed from tissues by plasma high-density lipoprotein (HDL) and transported to the liver, where it is eliminated from the body either unchanged or after conversion to bile acids in the process known as reverse cholesterol transport (see Chapter 25). Cholesterol is a major constituent of gallstones. However, its ...

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