Biomedical Background

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2.1. Structure, Classes, and Metabolism of Lipoproteins

Medieval physicians first observed lipoproteins (milky serum) in association with diabetes mellitus, nephrotic syndrome, and overindulgence of alcohol. In the early 1900s studies focused on the metabolism of plasma cholesterol and triglycerides. This approach quickly gave way to the study of the various lipoprotein classes after it was recognized that lipids and cholesterol were merely cargo and that apolipoproteins on the surface of lipo-protein particles were involved in their metabolism.

All of the major lipoprotein particles consist of a shell of amphipathic proteins (apolipoproteins), unesterified cholesterol and phospholipids (hydrophilic on one face and hydrophobic on the other), and a core of triglycerides and cholesterol esters. However, the concentration and characteristics of these particles differ as shown in Table 1. They are classified according to increasing density; chylomicrons (<0.95 g/mL), very low-density lipoproteins (VLDL, 0.95-1.006 g/mL), intermediate-density lipoproteins (IDL, 1.006-1.019), low-density lipoproteins (LDL, 1.019-1.063), and high-density lipoproteins (HDL, 1.063-1.210). Chylomicrons, which are synthesized by and released from the intestinal epithelial cells, consist of more than 80% of triglycerides and are responsible for transporting dietary fat. After release from the epithelial cells, the chylomicrons are metabolized to remnants that are composed mainly of cholesterol. The remnants bind to the hepatic chylomicron-remnant receptor and enter the liver cells, where the proteins are catabolized and cholesterol released. VLDL is a large triglyceride rich particle synthesized by the liver. Normally most of the VLDL is converted to smaller LDL particles through the "VLDL remnants" known as IDL. LDL, a small cholesterol-rich lipoprotein containing only apolipoprotein B-100, has a longer half-life than its precursors, VLDL and IDL. LDL accounts for about 70% of total cholesterol in plasma and is removed from plasma by LDL receptors, which are specific for Apo B-100. The rate of uptake determines plasma LDL concentration and therefore the measured plasma cholesterol concentration. LDL delivers cholesterol to all nucleated cells via endocytosis by the LDL-receptor. HDL, on the other

Table 1

Composition and Properties of Major Lipoprotein Classes

Table 1

Composition and Properties of Major Lipoprotein Classes

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