Spherical macromolecular complexes of lipids and proteins, known as plasma lipoproteins, encompass chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). These lipoprotein particles vary in terms of their lipid and protein composition, size, density, and site of origin. It should be noted that the actual content of apolipoproteins and lipids in each particle class may fluctuate due to the continuous interchange. The primary functions of lipoproteins are to keep lipids soluble during plasma transportation and to efficiently transport their lipid contents to and from tissues. However, humans have a less efficient transport system compared to other animals, resulting in gradual lipid (particularly cholesterol) deposition in tissues.

Lipoproteins consist of a neutral lipid core containing TAG and cholesteryl esters, surrounded by a shell composed of amphipathic apolipoproteins, phospholipids, and nonesterified cholesterol. The amphipathic compounds are arranged in a way that exposes their polar portions on the lipoprotein surface, allowing the particle to be soluble in aqueous solution. The lipoproteins acquire TAG and cholesterol from either the diet (exogenous source) or de novo synthesis (endogenous source). The cholesterol content of plasma lipoproteins is commonly measured in fasting blood, with the total cholesterol being the sum of LDL-C, HDL-C, and VLDL-C (where VLDL-C is calculated by dividing TAG by 5, as the TAG/cholesterol ratio in VLDL is 5/1). The target value for total cholesterol is less than 200 mg/dl.

Lipoprotein particles differ in size and density. Chylomicrons have the lowest density, largest size, highest lipid percentage (as TAG), and lowest protein percentage. VLDL and LDL are progressively denser and have higher protein-to-lipid ratios. HDL particles, on the other hand, are the smallest and densest. The electrophoretic mobility or density-based ultracentrifugation can be used to separate plasma lipoproteins.

Apolipoproteins, which are associated with lipoprotein particles, serve various functions such as providing recognition sites for cell-surface receptors and acting as activators or coenzymes for enzymes involved in lipoprotein metabolism. Certain apolipoproteins are indispensable structural components of the particles and cannot be removed, as the particles cannot be formed without them. Others can freely transfer between lipoproteins. Apolipoproteins are categorized into different major classes denoted by letters, each with subclasses (e.g., apolipoprotein [apo] C-I, apo C-II, and apo CIII). It should be noted that not all functions of the apolipoproteins have been fully elucidated.

Chylomicrons are synthesized in the intestinal mucosal cells and transport dietary (exogenous) TAG, cholesterol, fat-soluble vitamins, and cholesteryl esters to peripheral tissues. TAG accounts for approximately 90% of the lipids in a chylomicron.
The plasma lipoproteins are spherical macromolecular complexes of lipids and proteins (apolipoproteins). The lipoprotein particles include chylomicrons, verylow-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, density (Fig. 18.13), and site of origin. [Note: Because lipoprotein particles constantly interchange lipids and apolipoproteins, the actual apolipoprotein and lipid content of each class of particles is somewhat variable.] Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma and to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a gradual deposition of lipid (especially cholesterol) in tissues.
A. Composition
Lipoproteins are composed of a neutral lipid core (containing TAG and cholesteryl esters) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified (free) cholesterol (Fig. 18.14). These amphipathic compounds are oriented such that their polar portions are exposed on the surface of the lipoprotein, thereby rendering the particle soluble in aqueous solution. The TAG and cholesterol carried by the lipoproteins are obtained either from the diet (exogenous source) or from de novo synthesis (endogenous source). [Note: The cholesterol (C) content of plasma lipoproteins is now routinely measured in fasting blood. Total C = LDL-C + HDL-C + VLDL-C, where VLDL-C is calculated by dividing TAG by 5 because the TAG/cholesterol ratio is 5/1 in VLDL. The goal value for total cholesterol is <200 mg/dl.] 1.
Size and density: Chylomicrons are the lipoprotein particles lowest in density and largest in size and that contain the highest percentage of lipid (as TAG) and the lowest percentage of protein. VLDL and LDL are successively denser, having higher ratios of protein to lipid. HDL particles are the smallest and densest. Plasma lipoproteins can be separated on the basis of their electrophoretic mobility, as shown in Figure 18.15, or on the basis of their density by ultracentrifugation.
2.
Apolipoproteins: The apolipoproteins associated with lipoprotein particles have a number of diverse functions, such as providing recognition sites for cell-surface receptors and serving as activators or coenzymes for enzymes involved in lipoprotein metabolism. Some of the apolipoproteins are required as essential structural components of the particles and cannot be removed (in fact, the particles cannot be produced without them), whereas others are transferred freely between lipoproteins. Apolipoproteins are divided by structure and function into several major classes, denoted by letters, with each class having subclasses (for example, apolipoprotein [apo] C-I, apo C-II, and apo CIII). [Note: The functions of all the apolipoproteins are not yet known.]
B. Chylomicron metabolism
Chylomicrons are assembled in intestinal mucosal cells and carry dietary (exogenous) TAG, cholesterol, fat-soluble vitamins, and cholesteryl esters to the peripheral tissues (Fig. 18.16). [Note: TAG account for close to 90% of the lipids in a chylomicron.] 1.