Very-low-density lipoproteins synthesis

In the liver, cholesterol has three major fates conversion to bile acids, secretion into the blocKlstream (packaged in lipoproteins), and insertion into the plasma membrane. Conversion of cholesterol to cholic acid, one of the bile acids, requires about 10 enzymes. The rate of bile synthesis is regulated by the first enzyme of the pathway, cholesterol la-hydioxylase, one of the cytochrome P450 enzymes (see the section on Iron in Chapter 10), Cholesterol, mainly in the form of cholesteryl esters, is exported to other organs, after packaging in particles called very-low-density lipoproteins. Synthesis of cholesteryl esters is catalyzed by acyl CoA cho-Jesteroi acy(transferase, a membranc bound enzyme of the ER, Free cholesterol is used in membrane synthesis, where it appears as part of the walls of vesicles in the cytoplasm. These vesicles travel to the plasma membrane, where subsequent fusion results in incorporation of their cholesterol and phospholipids into the plasma membrane. 

Fibric acid derivatives, the third group of antihyperlipi-demic drugs, work in a variety of ways. Clofibrate (Atromid-S), acts to stimulate the liver to increase breakdown of very-low-density lipoproteins (VLDL) to low-density lipoproteins (LDL), decreasing liver synthesis of... 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Figure 25-6. The synthesis of very low density lipoprotein (VLDL) in the liver and the possible loci of action of factors causing accumulation of triacylglycerol and a fatty liver. (EFA, essential fatty acids FFA, free fatty acids ...

Increases triglyceride synthesis and very-low-density lipoprotein formation... 

Synthesis of lipids from carbohydrates is an efficient process, which occurs largely in the liver and also in intestinal epithelial cells.6 The newly synthesized triacylglycerols, together with smaller amounts of phospholipids and cholesterol, combine with specific apolipoproteins, which are also synthesized in the liver, to form very low density lipoprotein (VLDL) particles which are secreted into the blood stream. 

Fatty liver refers to the abnormal accumulation of fat in hepatocytes. At the same time there is a decrease in plasma lipids and lipoproteins. Although many toxicants may cause lipid accumulation in the liver (Table 14.1), the mechanisms may be different. Basically lipid accumulation is related to disturbances in either the synthesis or the secretion of lipoproteins. Excess lipid can result from an oversupply of free fatty acids from adipose tissues or, more commonly, from impaired release of triglycerides from the liver into the plasma. Triglycerides are secreted from the liver as lipoproteins (very low density lipoprotein, VLDL). As might be expected, there are a number of points at which this process can be disrupted. Some of the more important ones are as follows (Figure 14.1) ... 

Very-Low-Density Lipoproteins (VLDL) are less dense than chylomicrons. They contain more protein, although lipids (fatty acids, cholesterol and phospholipid, in that order) still make up 90 to 95 percent of their weight. Low-density lipoproteins (LDLs) are about 85 percent lipid by weight and contain more cholesterol than any other kind of lipid. VLDL and LDL contain large amounts of Apolipoprotein B. The VLDL and LDL are sometimes referred to as bad cholesterol because elevated serum concentrations of these lipoproteins correspond with a high incidence of artery disease (stroke and heart disease). The LDLs carry cholesterol and fatty acids to sites of cellular membrane synthesis. 

Synthesis of very low density lipoprotein Increase Liver... 

Figure 26.15. Site of Cholesterol Synthesis. Electron micrograph of a part of a liver cell actively engaged in the synthesis and secretion of very low density lipoprotein (VLDL). The arrow points to a vesicle that is releasing its content of VLDL particles. [Courtesy of Dr. George Palade.]...

Figure 30.13. Synthesis and Degradation of Triacylglycerols by Adipose Tissue. Fatty acids are delivered to adipose cells in the form of triacylglycerols contained in very low density lipoproteins (VLDLs).

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