TRIGLYCERIDES, CHOLESTEROL, AND OTHER LIPIDS

33 TRIGLYCERIDES, CHOLESTEROL, AND OTHER LIPIDS



1 Define the following terms: lipid, lipoprotein, apolipoprotein, triglyceride, cholesterol, fatty acid, hyperlipemia, hyperlipidemia, hyperlipoproteinemia, and lipemia.



a. Lipid: class of compounds that are insoluble in water and soluble in organic solvents.

b. Lipoprotein: complex that is composed of a core of hydrophobic lipids (triglycerides) covered by a layer of phospholipids, apolipoproteins, and cholesteryl esters; the form in which lipids are transported in the blood. Four main classes are (1) chylomicrons, (2) very-low-density lipoproteins (VLDLs), (3) low-density lipoproteins (LDLs), and (4) high-density lipoproteins (HDLs). Some classifications include intermediate-density lipoproteins (IDLs) between VLDL and LDL molecules.

c. Apolipoprotein: protein component (apoprotein) of a lipoprotein. Five major families are designated apolipoprotein A, B, C, D, and E.

d. Triglyceride: storage form of lipids composed of three molecules of fatty acids bound with one molecule of glycerol. The molecule is more appropriately called triacylglycerol but is referred to as “triglyceride” in most medical literature.

e. Cholesterol: steroid alcohol synthesized in hepatocytes that is used to make steroidal molecules and is degraded to bile acids in hepatocytes.

f. Fatty acid: chain of carbon atoms with a carboxylic acid group at one end. Fatty acids combine with glycerol to form fat (e.g., mono-, di-, and triacylglycerol).

g. Hyperlipemia and hyperlipidemia: general terms that indicate increased concentration of lipids in the blood due to increased concentrations of free fatty acids, hypertriglyceridemia, hypercholesterolemia, or hyperlipoproteinemia.

h. Hyperlipoproteinemia: increased concentration of lipoproteins in the blood.

i. Lipemia: can be used as a synonym for hyperlipidemia and hyperlipoproteinemia; more often defined as the lactescent (milky) appearance of serum or plasma due to increased concentrations of large lipoprotein molecules.


2 Which two lipid compounds in the plasma of domestic mammals are most commonly measured by clinical laboratory assays?


The two major analytes are cholesterol and triglyceride (triacylglycerol). The triglyceride molecules and almost all the cholesterol molecules circulate in plasma lipoproteins.


Serum cholesterol concentration is the total cholesterol concentration. The reacting cholesterol molecules (cholesterol and cholesterol esters) were within lipoproteins, typically in cholesterol-rich LDL and HDL molecules. Likewise, serum triglyceride concentration is the total triglyceride concentration. The reacting triglyceride molecules were mostly within triglyceride-rich lipoproteins (chylomicrons, VLDLs, IDLs).



3 How are lipoproteins classified?


Lipoproteins are classified by either their electrophoretic mobility or by their density relative to water. Their electrophoretic migrations and their densities depend on their compositions. In the electrophoretic classification the large and poorly charged chylomicrons do not migrate from the application point (end of gamma region). However, the smaller lipoproteins with their external coating of charged protein and lipid molecules migrate into the alpha (α) and beta (β) regions, as designated by routine protein electrophoresis in which molecules are stained with a protein stain instead of a lipid stain. In the density classification, which uses the common lipoprotein names (e.g., VLDL, IDL), the lipoproteins are grouped by their relative density compared with water (Table 33-1).



Table 33-1 Classification, Content, and Properties of Human Lipoproteins

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4 How do the lipoproteins of human serum differ from the serum lipoproteins of domestic mammals?


The composition of the lipoproteins in human and domestic mammalian sera is similar; however, the relative amounts of the lipoproteins differ between species. For example, human sera typically have more VLDL and LDL molecules than HDL. However, dog sera typically have more HDL molecules than VLDL or LDL molecules.



5 Lactescence in lipemic blood samples is primarily caused by high concentrations of which lipoproteins?


The largest lipoproteins, chylomicrons and VLDLs, cause the lactescence (milky appearance) or turbidity seen in lipemic blood samples. These lipoproteins are large enough to interfere with light transmission through the serum or plasma and thus create lactescence.



6 How do clinical laboratory assays measure serum or plasma cholesterol and triglyceride concentrations?


Cholesterol assays typically are enzymatic assays that hydrolyze cholesterol esters and use cholesterol oxidase to oxidize cholesterol and generate hydrogen peroxide (H2O2), which reacts with an indicator dye. Other methods use oxygen-sensing electrodes to measure oxygen consumption. High serum concentrations of bilirubin and ascorbic acid may interfere with some assays.


Triglyceride assays involve reactions that generate products that are detectable by spectrophotometry. The glycerin that coats some red-top collection tubes interferes with some triglyceride assays.



7 What three major changes or alterations in physiologic processes produce hyperlipidemia?


Hyperlipidemia occurs when one or more of the following processes occur:


a. Increased production of lipoproteins by hepatocytes

b. Defective intravascular processing of lipoproteins, including defective lipolysis that is catalyzed by lipoprotein lipase

c. Defective cellular uptake of lipoproteins or lipoprotein remnants


8 What are the different lipases and what are their actions?


The breakdown of lipids in the body involves the following lipases:


a. Gastric lipase is produced by gastric mucosal cells and degrades ingested triglyceride.

b. Pancreatic lipase (triacylglycerol lipase) is produced by pancreatic acinar cells and catalyzes the hydrolysis of dietary triglyceride in the intestine. The action of pancreatic lipase requires the emulsification of dietary lipids by bile acids.

c. Lipoprotein lipase (LPL) is produced mainly by extrahepatic cells, including adipocytes and myocytes. Once produced, LPL migrates to the luminal surface of endothelial cells, where it catalyzes the hydrolysis of triglycerides in chylomicrons, VLDLs, and IDLs. The movement of LPL to the luminal surface is an insulin-dependent process.

d. Hepatic lipase is produced by hepatocytes, is present on endothelial cells of hepatic sinusoids, and hydrolyzes triglyceride in LDL molecules.

e. Hormone-sensitive lipase in adipocytes catalyzes the hydrolysis of stored triglyceride, which results in the liberation of fatty acids; it is stimulated by epinephrine and glucagon.

f. Lysosomal acid lipase is an intracellular lipase that catalyzes the hydrolysis of cholesterol esters.


9 What major physiologic processes result in the formation and degradation of lipoproteins?


Figure 33-1 illustrates and describes the major metabolic pathways for endogenous and exogenous lipids.


image

Figure 33-1 The three major processes that affect lipoprotein concentrations and thus triglyceride (TG) and cholesterol (Chol) concentrations are (1) synthesis of chylomicrons in enterocytes and very-low-density lipoprotein (VLDL) molecules in hepatocytes, (2) lipoprotein lipase (LPL)–catalyzed lipolysis on endothelial cell membranes, and (3) hepatocyte clearance of lipoprotein remnants. There are two major metabolic pathways for lipids, one for endogenous and one for exogenous lipids.


Exogenous or dietary lipids. Ingested TG in the presence of bile acids and pancreatic lipase undergoes lipolysis to form monoglyceride (MG) and fatty acid (FA). After absorption by enterocytes, MG and FA are reassembled into TG. Enterocytes also produce cholesterol ester (CE), phospholipids, and apolipoproteins A and B and then assemble the molecules into TG-rich lipoproteins called chylomicrons. The chylomicrons enter lymphatic vessels and then blood through the thoracic duct. In blood, chylomicrons obtain C and E apolipoproteins from circulating high-density lipoprotein (HDL). In the presence of insulin, apolipoprotein C-II activates LPL (on endothelial cell membranes), which catalyzes the lipolysis of TG to generate FA. The FA enters adipocytes to be stored in TG or enters muscle fibers (or other cells) to undergo oxidation to generate energy. After removal of most TG molecules, the chylomicron remnants are cleared from plasma by hepatocytes in a process involving B apolipoproteins.


Endogenous lipids produced by hepatocytes. Hepatocytes produce TG, phospholipids, apolipoproteins, and CE, which may form from dietary cholesterol or de novo synthesis.


TG-rich VLDL molecules are assembled in hepatocytes and secreted into sinusoidal blood. In the presence of insulin, apolipoprotein C-II on VLDLs activates LPL on endothelial cells to initiate lipolysis and liberation of FA from TG. As VLDL molecules lose TG, they become denser to form intermediate-density lipoprotein (IDL), which may also undergo additional lipolysis to form low-density lipoprotein (LDL). LDL molecules deliver cholesterol to many cells for maintenance of cell membranes or steroid hormone synthesis. Hepatocyte clearance of LDL involves the action of hepatic lipase and the binding of a cholesterol-rich remnant to a B apolipoprotein receptor on hepatocytes. LDLs are also removed by macrophages in either receptor-mediated or non–receptor-mediated processes.


Discoid HDL molecules are produced by hepatocytes and then acquire their complete spherical form in blood. HDLs have two major functions: (1) serve as a source of C and E apolipoproteins for other lipoproteins and (2) accept cholesterol from plasma membranes or lipoproteins and transport it to hepatocytes for reutilization or degradation.


Shaded letters A, B, C, and E, apolipoproteins A, B, C, and E, respectively; LPS, pancreatic lipase; PL, phospholipid; AcCoA, acetyl coenzyme A; ATP, adenosine triphosphate.


(Modified from Stockham SL, Scott MA. Fundamentals of veterinary clinical pathology, Ames, 2002, Iowa State Press.)

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Aug 26, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on TRIGLYCERIDES, CHOLESTEROL, AND OTHER LIPIDS

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