Advan. Physiol. Edu. 28: 105-106, 2004;
doi:10.1152/advan.00048.2003
1043-4046/04 $5.00
ADV PHYSIOL EDUC 28:105-106, 2004
© 2004 American Physiological Society
HOW WE TEACH
Understanding lipoproteins as transporters of cholesterol and other lipids
Kyle D. Biggerstaff and
Joshua S. Wooten
Exercise Physiology Laboratory, Department of Kinesiology, Texas Woman’s University, Denton, Texas 76204
Address for reprint requests and other correspondence: K. D. Biggerstaff, Exercise Physiology Laboratory, Dept. of Kinesiology, Texas Woman’s University, Denton, TX 76204–5647 (E-mail: kbiggerstaff{at}mail.twu.edu)
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Abstract
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A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than transporters of lipid. Describing lipoproteins as particles that are composed of lipid and protein and illustrating the variation in particle density that is determined by the constantly changing lipid and protein composition clarifies the metabolic pathway and physiological function of lipoproteins as lipid transporters. Such a description will also suggest the critical role played by apolipoproteins in lipid transport. The clarification of lipoproteins as particles that change density will help students understand the nomenclature used to classify lipoproteins as well.
Key words: high-density lipoprotein-cholesterol; low-density lipoprotein-cholesterol; density; apolipoprotein
HYPERCHOLESTEROLEMIA is a major risk factor for cardiovascular disease. As such, lipoproteins and their metabolism are frequently discussed in a wide variety of undergraduate biological and health courses. Commonly, class discussion and examination responses suggest that students oversimplify the role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) as being little more than "bad" and "good" forms of cholesterol. After this type of description, students understandably consider the various lipoproteins as types of cholesterol rather than as transporters of cholesterol and other lipids. As an example of this perception, it is not uncommon for a student to ask a question about the types of food that contain "good" or "bad" cholesterol. This misconception about the nature of lipoproteins and cholesterol creates considerable difficulties when trying to understand lipoproteins as transporters of lipid that are substantially influenced by lifestyle behaviors like high-fat diet, inactive lifestyle, and cigarette smoking.
Students are often confused by the metabolism and function of lipoproteins. Understanding that HDL-cholesterol is "good" and excessive LDL-cholesterol is "bad" is easily learned, but more demanding is a detailed understanding of the function of lipoprotein fractions. By understanding the importance of the density of lipoprotein particles and apolipoproteins, metabolism and function of lipoproteins become clear. The following description helps simplify the complexities of lipoproteins.
Lipoproteins are molecules that have a globular shape and are a combination of lipid and protein. The lipoprotein particle core is composed of lipid, primarily triacylglycerol and cholesteryl ester. The plasma membrane is composed of phospholipids, a small amount of free cholesterol, and proteins called apolipoproteins. The apolipoproteins may be integral components of the plasma membrane or they may be peripheral to the plasma membrane. The density of a lipoprotein particle is determined by the relative amounts of lipid and protein contained in the particle (Table 1) (1, 2) . Rather than describing density only as mass divided by volume, the following description helps students understand the importance of the lipid content, apolipoproteins, and nomenclature as they relate to lipoprotein function.
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Table 1 Major lipoprotein fraction density range and percentage of total mass that is cholesterol, triglyceride, phospholipid, and protein
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Most students understand that oil and water do not mix. This point is made clear by asking what happens when water is poured into a skillet with grease remaining in it after cooking. Obviously, the grease will float. Conversely, a lean piece of meat that is placed into the water-filled skillet will sink. The different densities of the grease (lipid) and the lean meat (protein) determine whether or not they will float or sink. This description will help clarify the density-based nomenclature used to classify different lipoprotein fractions, and it will also help illustrate the role of apolipoproteins as lipid transporters. By describing that each lipoprotein fraction caries different relative amounts and types of lipid along with differing compositions of apolipoproteins, it becomes clear that each lipoprotein fraction will have a density that falls within a set range (Table 1).
Appreciating that the density of each lipoprotein particle changes throughout the metabolic pathway is also critical for understanding lipoprotein metabolism (Fig. 1). Lipoproteins interact with lipase enzymes (lipoprotein lipase and hepatic lipase), which cleave triacylglycerol in the lipoprotein core into three fatty acids and glycerol, thus making the lipoproteins more dense (2). Lipoproteins also interact with lipid transfer proteins. Cholesteryl ester transfer protein transports cholesteryl ester from HDL to LDL while triacylglycerol is removed from LDL and transported to HDL. Additionally, lecithin:cholesterol acyltranferase esterifies and transports free cholesterol to the HDL core, resulting in decreased HDL density. Certain apolipoproteins are cofactors for some of these enzymatic reactions. Apolipoproteins also act as ligands for specific lipoprotein receptors at the tissue (1–3). As a result of the ever-changing lipid and protein content of lipoproteins, the density of each lipoprotein is clearly in a constant state of flux.
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FIG. 1 General description of lipoproteins with higher or lower densities, direction of triglyceride and cholesterol movement, and apolipoprotein components to achieve these densities. Apo, apolipoproteins; E, enzyme; Chol, cholesterol; Tg, triglyceride; [PL], phospholipid concentration; [Tg], Tg concentration; [CE], cholesterol ester concentration.
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The nomenclature used for lipoproteins is purely a function of the density of each particle. Two lipoprotein fractions are primarily involved in transport of lipid to peripheral tissues, very low density lipoproteins (VLDL) from the liver and chylomicrons from the intestinal tract. As lipid is removed from these two fractions, the density of each fraction increases, thereby transforming VLDL into intermediate-density lipoprotein (IDL) and ultimately LDL, and chylomicrons into chylomicron remnants. A third type of lipoprotein, HDL, is primarily involved in returning lipid, largely cholesterol, to the liver in a process called reverse cholesterol transport. As HDL increases in cholesterol content, the density of the particle decreases. Two primary subfractions of HDL have been classified as the higher-density HDL3, and the less dense, more lipid-filled HDL2. Typically, after interacting with hepatic lipase, HDL2 reverts back to HDL3 as a function of the decreased lipid remaining in the lipoprotein core (2). Because excessive delivery of cholesterol to the periphery by the VLDL-LDL series leading to atherosclerotic plaque accumulation is not uncommon in the United States, LDL-cholesterol has been described, and overly simplified, as "bad cholesterol" and HDL-cholesterol as "good cholesterol."
Atherosclerosis is a primary outcome of elevated LDL-cholesterol and depressed HDL-cholesterol concentrations. Recent investigations are also suggesting that smaller, denser lipoproteins are associated with increased risk of atherosclerotic development (4). So that students can begin to understand the biochemical goals of lifestyle modifications and pharmacological interventions to improve lipoprotein profiles, it is important for them to understand the critical role of lipoproteins as transporters of lipid rather than simply as good or bad forms of cholesterol. An introductory discussion of density with respect to lipids and proteins will help clarify students’ understanding of lipoproteins. Following this discussion, students will be more likely to understand the function of each lipoprotein fraction. Furthermore, grasping the normal physiology of lipoproteins will promote greater understanding of the pathophysiology of hypercholesterolemia and atherosclerosis.
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REFERENCES
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- Durstine JL and Haskell WL. Effects of exercise training on plasma lipids and lipoproteins. In: Exerc Sport Sci Rev. Baltimore, MD: Am. Coll. Sports Med., 1994, vol. 22, chapt. 15, p. 477–521.
- Grandjean P and Crouse SF. Lipid and lipoprotein disorders. In: Clinical Exercise Physiology: Applications and Physiological Principles, edited by Lemura LM and von Duvillard SP. Philadelphia, PA: Lippincott Williams & Wilkins, 2004, chapt. 5, p. 55–86.
- Marks DB, Marks AD, and Smith CM. Basic Medical Biochemistry: A Clinical Approach. Baltimore, MD: Williams and Wilkins, 1996, chapt. 34, p. 525–544.
- Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM, and Hennekens CH. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 276: 882–888, 1996.[Abstract]
Copyright © 2004 by the American Physiological Society.
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