BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 14. LIPID METABOLISM

14.2. Plasma Lipoproteins

Besides chylomicrons, other lipoprotein complexes function in the Blood, which are secreted primarily by the parenchymal Cells of the Liver. The Biosynthesis of lipid and protein components of Other types of Lipoproteins, their assembly, Intracellular Transport, and secretion into the blood are carried out in liver cells in the same manner as in the intestinal mucosal epithelial cells.

Fats, Cholesterol and its esters, Phospholipids, and apoproteins all participate in The formation of all forms of blood lipoproteins, although The ratio of these components varies for each complex (Table 14.1). The Synthesis of Plasma lipoproteins is regulated by Hormones and dietary composition. For instance, a carbohydrate-rich diet stimulates fatty acid synthesis, whereas a high-fat diet inhibits it. Apoproteins play a crucial role in the formation and METABOLISM of lipoproteins. Apoproteins A-I, A-II, B, C-I, C-II, C-III, D, E, and F perform structural and regulatory Functions as components of various lipoproteins.

Based on their physicochemical characteristics, plasma lipoproteins are divided into four classes:

✵ high-density lipoproteins, or α-lipoproteins, which migrate during Electrophoresis along with α-globulins;

✵ low-density lipoproteins, or β-lipoproteins, which migrate in an electric field along with β-globulins;

✵ very low-density lipoproteins, or pre-β-lipoproteins, which migrate ahead of the β-globulin fraction;

✵ chylomicrons, which do not migrate in an electric field.

Plasma lipoproteins share a common structural Organization: hydrophobic molecules of triacylglycerols and cholesterol esters are located inside a micellar Structure with a diameter of 7-1000 nm, while the outer layer, which is ~2 nm thick, consists of Proteins (apoproteins) and phospholipids that form a hydrophilic shell stabilizing the hydrophobic micellar structure in an aqueous environment.

Class="center">Table 14.1

Chemical Composition and Physical Properties of Plasma Lipoproteins

Note: PL - phospholipids, Ch - cholesterol, CCh - cholesterol esters, TAG - triacylglycerols, ρ - specific gravity, d - micelle diameter, HDL - high-density lipoproteins, LDL - low-density lipoproteins, VLDL - very low-density lipoproteins, CM - chylomicrons.

Among the major plasma lipoproteins, high-density and very low-density lipoproteins are synthesized in the liver.

Nascent very low-density lipoproteins secreted by hepatocytes into the blood are converted into mature particles after interacting with high-density lipoproteins and acquiring apoprotein C-II from them. The Catabolism of very low-density lipoproteins, with a half-life of 2-4 hours, occurs in the capillaries of adipose, Muscle, and other Tissues via the Enzymatic Hydrolysis of their triacylglycerols by lipoprotein lipase. During this process, their triacylglycerol content decreases from 80% to 10%, while the relative concentration of cholesterol, especially its esters, increases. This is accompanied by a reduction in particle diameter and an increase in their relative density; in other words, The conversion of very low-density lipoproteins into low-density lipoproteins takes place directly in the bloodstream.

Thus, very low-density lipoproteins serve as a transport form for endogenous triacylglycerols delivered from the liver to peripheral tissues, where they are assimilated.

The assimilation of low-density lipoproteins occurs in fibroblasts, lymphoid cells, and other cells incapable of synthesizing cholesterol. The cholesterol requirements of these cells are met by low-density lipoproteins, which enter them via endocytosis after binding to specific receptors on the outer Cell surface. Receptor efficiency is determined by the presence of apoprotein B within low-density lipoproteins and the concentration of receptors on The Cell membrane. Low-density lipoproteins entering the cell in this manner fuse with Lysosomes and are degraded by lysosomal Hydrolases—lipases and proteases—into building blocks such as cholesterol and Amino Acids, which can be utilized for the synthesis of membranes and other cellular structures. Therefore, low-density lipoproteins act as a transport vehicle for cholesterol and its esters, delivering these lipids to cholesterol-depleted cells.

High-density lipoproteins synthesized in the liver actively participate in the exchange of lipids and apoproteins between the liver, plasma lipoproteins, and Biomembranes. Nascent high-density lipoprotein particles serve as a convenient substrate for the immobilization of the plasma enzyme lecithin-cholesterol acyltransferase (LCAT), which is activated by apoprotein A₁. The biological function of high-density lipoproteins and LCAT is to regulate free cholesterol Homeostasis in cell membranes. The regulatory mechanism involves transferring excess cholesterol generated in cell membranes to nascent high-density lipoproteins. On the surface of high-density lipoprotein particles, cholesterol is esterified by LCAT, which catalyzes The transfer of an acyl radical from the phosphatidylcholine of the outer layer of high-density lipoprotein particles to cholesterol. The resulting cholesterol esters form the inner Hydrophobic core of mature high-density lipoprotein particles, through which they are eventually transported to The Liver and metabolized.

Thus, plasma lipoproteins facilitate the dynamic exchange of exogenous and endogenous lipids between the intestine, liver, and peripheral tissues, supplying the tissues with structural and energetic metabolic substrates.