Cholesterol, Triglycerides, and Associated Lipoproteins - Clinical Methods - NCBI Bookshelf
Two types of proteins called “lipoproteins” carry cholesterol in the blood: LDL and HDL. High LDL levels raise your risk for heart disease and. A lipoprotein is a biochemical assembly whose primary purpose is to transport hydrophobic lipid (a.k.a. fat) molecules in water, as in blood or extracellular fluid. They have a single-layer phospholipid and cholesterol outer shell, with the lipoproteins, according to density / size (an inverse relationship), compared with the. Blood levels of total cholesterol, triglycerides and high-density lipoprotein cholesterol Examples of such measurements are LDL particle number (LDL-P), A meta-analysis of prospective studies provided evidence of a link between Lp( a).
Heart disease occurs because the coronary arteries supplying the heart are a major site where atherosclerotic plaques form. The liver is central to the regulation of cholesterol levels in the body.
Not only does it synthesize cholesterol for export to other cells, but it also removes cholesterol from the body by converting it to bile salts and putting it into the bile where it can be eliminated in the feces. Furthermore, the liver synthesizes the various lipoproteins involved in transporting cholesterol and other lipids throughout the body. Cholesterol synthesis in the liver is under negative feedback regulation. Increased cholesterol in a hepatocyte leads to decreased activity of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis.
Types of Lipoproteins Lipoproteins are particles that contain triacylglycerol TAGcholesterol, phospholipids and amphipathic proteins called apolipoproteins. You can refresh your memory about the structure of lipoproteins by visiting the webpage Lipoproteins from fall quarter. Lipoproteins can be differentiated on the basis of their density, but also by the types of apolipoproteins they contain. The degree of lipid in a lipoprotein affects its density—the lower the density of a lipoprotein, the more lipid it contains relative to protein.
The figure below summarizes the fates of lipoproteins produced by the liver. Refer to it as you read about the different lipoproteins. Two types of lipoproteins are triglyceride-rich: Chylomicrons are synthesized by enterocytes from lipids absorbed in the small intestine.
HDL (Good), LDL (Bad) Cholesterol and Triglycerides
VLDL is synthesized in the liver. The function of these lipoproteins is to deliver energy-rich triacylglycerol TAG to cells in the body pink pathway.
TAG is stripped from chylomicrons and VLDL through the action of lipoprotein lipase, an enzyme that is found on the surface of endothelial cells. This enzyme digests the TAG to fatty acids and monoglycerides, which can then diffuse into the cell to be oxidized, or in the case of an adipose cell, to be re-synthesized into TAG and stored in the cell. LDL delivers cholesterol to cells in the body. The NIH Concensus Conference has recently revised the values concerning cholesterol, however, in view of clear evidence of an increased risk of coronary atherosclerosis in persons falling in the 75th to 90th percentiles.
Cholesterol levels are fairly constant, but triglyceride levels fluctuate considerably from day to day and are highest 1 to 4 hours after meals.
LDL and HDL Cholesterol: "Bad" and "Good" Cholesterol
Collection of blood for triglyceride testing should be done after a hour fasting period, when chylomicrons have ordinarily been cleared from the circulation. Measurements must be ideally done while the patients are on their usual diet and taking no medications that could alter blood lipid levels.
Sampling should not be performed during periods of stress or within 6 weeks after a major illness, such as an acute myocardial infarction, as plasma cholesterol may be reduced and triglyceride levels increased in these instances. The standard chemical determination for plasma cholesterol is the Abell-Kendall A-K technique, which involves the Liebermann-Burchardt reaction after hydrolysis and extraction of cholesterol.
Samples for plasma cholesterol and triglyceride determinations are commonly analyzed by completely automated methods at clinical laboratories. As the results obtained at commercial laboratories differ systematically from those obtained by research methods, it is advisable to inquire how the method used by the particular laboratory compares with reference values, and to employ the same laboratory facility for serial measurements.
The best reference values available today for North American populations are those obtained in the Lipid Research Clinics Program, which surveyed 12, Americans aged 20 to 79 in the United States and Canada. Reference values for plasma total cholesterol were obtained by utilizing autoanalyzer systems to which either the ferric chloride—sulfuric acid method or the Liebermann-Burchardt test was adapted. A fluorometric analysis was utilized to determine triglyceride reference values.
Plasma high-density lipoprotein cholesterol HDL-C determination in this program was measured by the same procedures used for plasma total cholesterol, after precipitation of apoprotein B-containing lipoproteins in whole plasma LDL and VLDL by heparin—manganese chloride. This test could help to distinguish type 1 hyperlipoproteinemia creamy layer on top with clear infranatant from type 5 hyperlipoproteinemia creamy layer on top with turbid infranatant.Cholesterol Metabolism, LDL, HDL and other Lipoproteins, Animation
Lipoproteins can be separated by ultracentrifugation, precipitation, and electrophoresis. Lipoprotein fractions can be quantified by preparative or density-adjusted ultracentrifugation. This method is usually employed in elaborate studies and not as a routine clinical tool. The quantitative reference method employs precipitation and ultracentrifugation sequentially to determine each lipoprotein component.
Usually, measurement of plasma lipid levels is sufficient for evaluation of patterns of lipoprotein elevations. Occasionally paper electrophoresis of the plasma is helpful. The correspondence of electrophoretic fractions with lipoproteins is shown in Table Quantitative determination of apoproteins is performed in sophisticated laboratories utilizing radioimmunoassays for apoprotein AI and apoprotein B and isoelectric focusing for apoproteins C and E. Other specialized tests are: Basic Science Plasma lipoprotein particles contain variable proportions of four major elements: The varying composition of these elements determines the density, size, and electrophoretic mobility of each particle.
These factors in turn have been used for the clinical and biochemical classification of lipoprotein disorders. Schematically, lipoproteins have been described as globular or spherical units in which a nonpolar core lipid consisting mainly of cholesterol esters and triglycerides is surrounded by a layer containing phospholipids, apoproteins, and small amounts of unesterified cholesterol.
Apoproteins, in addition to serving as carrier proteins, have other important functions such as being co-factors for enzymes involved in lipoprotein metabolism, acting as specific ligands for binding of the particles to cellular receptor sites, and intervening in the exchange of lipid constituents between lipoprotein particles.
Lipoprotein - Wikipedia
The fact that all the cholesterol required by the body can be produced by biosynthesis points to the essential nature of this substance. As an estimated loss of 1. The role of lipoprotein particles is to transport all hydrophobic fat molecules, such as triacylglycerols a. The proteins which form these particles are synthesized and secreted into the extracellular water by both the small intestine and liver cells.
All cells use and rely on fats and cholesterol as building-blocks to create the multiple membranes that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems. The lipoprotein particles have hydrophilic groups of phospholipids, cholesterol, and apoproteins directed outward. Such characteristics make them soluble in the salt water-based blood pool. Triglyceride-fats and cholesteryl esters are carried internally, shielded from the water by the phospholipid monolayer and the apoproteins.
The interaction of the proteins forming the surface of the particles with enzymes in the blood; with each other; and with specific proteins on the surfaces of cells determines whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles. Regarding atheroma development and progression as opposed to regression, the key issue has always been cholesterol transport patterns, not cholesterol concentration itself.
It is divided into two pathways, exogenous and endogenousdepending in large part on whether the lipoprotein particles in question are composed chiefly of dietary exogenous lipids or whether they originated in the liver endogenousthrough de novo synthesis of triacylglycerols.
The hepatocytes are the main platform for the handling of triacylglycerols and cholesterol ; the liver can also store certain amounts of glycogen and triacylglycerols. While adipocytes are the main storage cells for triacylglycerols, they do not produce any lipoproteins. Exogenous pathway[ edit ] Simplified flowchart showing the essentials of lipoprotein metabolism. Bile emulsifies fats contained in the chymethen pancreatic lipase cleaves triacylglycerol molecules into two fatty acids and one 2-monoacylglycerol.
Lipoprotein(a). What is lipoprotein(a) and why is it important?
Enterocytes readily absorb these small molecules from the chymus. Inside of the enterocytes, fatty acids and monoacylglycerides are transformed again into triacylglycerides. Then these lipids i. These particles are then secreted into the lacteals in a process that depends heavily on apolipoprotein B