Липопротеины: структура, функции и метаболизм

Biochemical assembly whose purpose is to transport hydrophobic lipid molecules
proteins covalently linked to lipids, including bacterial/transmembrane "lipoproteins"

A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role. Plasma lipoprotein particles are commonly divided into five main classes, based on size, lipid composition, and apolipoprotein content: HDL, LDL, IDL, VLDL and chylomicrons. Subgroups of these plasma particles are primary drivers or modulators of atherosclerosis. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are sometimes also classified as lipoproteins, since they are formed by lipids and proteins.

Some transmembrane proteolipids, especially those found in bacteria, are referred to as lipoproteins; they are not related to the lipoprotein particles that this article is about. Such transmembrane proteins are difficult to isolate, as they bind tightly to the lipid membrane, often require lipids to display the proper structure, and can be water insoluble. Detergents are usually required to isolate transmembrane lipoproteins from their associated biological membranes.

Lipoproteins are complex particles that have a central hydrophobic core of non polar lipids, primarily cholesteryl esters and triglycerides. This hydrophobic core is surrounded by a hydrophilic membrane consisting of phospholipids, free cholesterol, and apolipoproteins. Plasma lipoproteins, found in blood plasma, are typically divided into five main classes based on size, lipid composition, and apolipoprotein content: HDL, LDL, IDL, VLDL and chylomicrons.

The handling of lipoprotein particles in the body is referred to as lipoprotein particle metabolism. It is divided into two pathways, exogenous and endogenous, depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through de novo synthesis of triglycerides. The hepatocytes are the main platform for the handling of triglycerides and cholesterol; the liver can also store certain amounts of glycogen and triglycerides. While adipocytes are the main storage cells for triglycerides, they do not produce any lipoproteins.

Bile emulsifies fats contained in the chyme, then pancreatic lipase cleaves triglyceride molecules into two fatty acids and one 2 monoacylglycerol. Enterocytes readily absorb the small molecules from the chymus. Inside of the enterocytes, fatty acids and monoacylglycerides are transformed again into triglycerides. Then these lipids are assembled with apolipoprotein B 48 into nascent chylomicrons. These particles are then secreted into the lacteals in a process that depends heavily on apolipoprotein B 48. As they circulate through the lymphatic vessels, nascent chylomicrons bypass the liver circulation and are drained via the thoracic duct into the bloodstream. In the blood stream, nascent chylomicron particles interact with HDL particles, resulting in HDL donation of apolipoprotein C II and apolipoprotein E to the nascent chylomicron. The chylomicron at this stage is then considered mature. Via apolipoprotein C II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes the hydrolysis of triglycerides that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially adipose and muscle, for energy and storage. The hydrolyzed chylomicrons are now called chylomicron remnants. The chylomicron remnants continue circulating the bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.

The liver is the central platform for the handling of lipids: it is able to store glycerols and fats in its cells, the hepatocytes. Hepatocytes are also able to create triglycerides via de novo synthesis. They also produce the bile from cholesterol. The intestines are responsible for absorbing cholesterol. They transfer it over into the blood stream. In the hepatocytes, triglycerides and cholesteryl esters are assembled with apolipoprotein B 100 to form nascent VLDL particles. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B 100. In the blood stream, nascent VLDL particles bump with HDL particles; as a result, HDL particles donate apolipoprotein C II and apolipoprotein E to the nascent VLDL particle. Once loaded with apolipoproteins C II and E, the nascent VLDL particle is considered mature. VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase. Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called low density lipoproteins (LDL), which contain a relatively high cholesterol content LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B 100 on the LDL particle. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.

Plasma lipoproteins may carry oxygen gas. This property is due to the crystalline hydrophobic structure of lipids, providing a suitable environment for O2 solubility compared to an aqueous medium.

It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in serum protein electrophoresis. This terminology is sometimes used in describing lipid disorders such as abetalipoproteinemia.

Lipoproteins, such as LDL and HDL, can be further subdivided into subspecies isolated through a variety of methods. These are subdivided by density or by the protein contents/ proteins they carry. The links of mechanisms between different lipoprotein isoforms and risk for cardiovascular diseases, lipoprotein synthesis, regulation, and metabolism, and related risks for genetic diseases are under active research, as of 2022.