Chylomicrons synthesis

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 4.10 Monoacylglycerol pathway for synthesis of triacylglycerol and formation of chylomicrons within the enterocyte.

LDL is catabolized chiefly in hepatocytes and other cells by receptor-mediated endocytosis. Cholesteryl esters from LDL are hydrolyzed, yielding free cholesterol for the synthesis of cell membranes. Cells also obtain cholesterol by synthesis via a pathway involving the formation of mevalonic acid by HMG-CoA reductase. Production of this enzyme and of LDL receptors is transcriptionally regulated by the content of cholesterol in the cell. Normally, about 70% of LDL is removed from plasma by hepatocytes. Even more cholesterol is delivered to the liver via IDL and chylomicrons. Unlike other cells,... 

VLDLs to fat and muscle tissue. The NADPH necessary for lipid synthesis is obtained by oxidation of glucose in the pentose phosphate pathway. Excess amino acids are converted to pyruvate and acetyl-CoA, which are also used for lipid synthesis. Dietary fats move via the lymphatic system, as chylomicrons, from the intestine to muscle and fat tissues. 

E. Formation of chylomicrons does not require protein synthesis in the intestinal mucosa. 

Correct answer = A. Pancreatic lipase hydrolyzes dietary triacylglycerol primarily to 2-monoacylglycerol plus two fatty acids. These products of hydrolysis can be absorbed by the intestinal mucosal cells. Bile salts do not inhibit release of fatty acids from triacylglycerol, but rather are necessary for the proper solubilization and hydrolysis of dietary triacylglycerol in the small intestine. Short- and medium-chain length fatty acids enter the portal circulation after absorption from the small intestine. Synthesis of apolipoproteins, especially apo B-48, is essential for the assembly and secretion of chylomicrons. 

Assembly of chylomicrons The enzymes involved in triacylglycerol, cholesterol, and phospholipid synthesis are located in Ihe smooth ER. Assembly of the apolipoproteins and lipid into chylomicrons requires microsomal triacylglycerol transfer protein (see p. 229), which loads apo B-48 with lipid. This occurs during transition from the ER to the Golgi, where the particles are packaged in secretory vesicles. These fuse with the plasma membrane releasing the lipoproteins, which then enter the lymphatic system and, ultimately, the blood. 

VLDLs are produced in the liver (Figure 18.17). They are composed predominantly of triacylglycerol, and their function is to carry this lipid from the liver to the peripheral tissues. There, the triacylglycerol is degraded by lipoprotein lipase, as discussed for chylomicrons (see p. 226). [Note "Fatty liver" (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic triacylglycerol synthesis and the secretion of VLDL. Such conditions include obesity, uncontrolled diabetes mellitus, and chronic ethanol ingestion.]... 

Effect of endocytosed cholesterol on cellular cholesterol homeostasis The chylomicron remnant-, IDL-, and LDL-derived cholesterol affects cellular cholesterol content in several ways (see Figure 18.20). First, HMG CoA reductase is inhibited by ttfi cholesterol, as a result of which, de novo cholesterol synthesis decreases. Second, synthesis of new LDL receptor protein is reduced by decreasing the expression of the LDL receptor gene, thus limiting further entry of LDL cholestrol into cells. [Note ... 

Increased triacylglycerol synthesis Triacylglycerol synthesis is favored because fatty acyl CoA is available both from de rxxo synthesis from acetyl CoA and from hydrolysis of the triacylglycerol component of chylomicron remnants removed from Ihe blood by hepatocytes (see p. 176). Glycerol 3-phosphate, Ihe... 

Increased synthesis of fatty acids De novo synthesis of fatty acids from acetyl CoA in adipose tissue is nearly undetectable in humans, except when refeeding a previously fasted individual. At other times, fatty acid synthesis in adipose tissue is not a major pathway (see Figure 24.5, G). Instead, most of the fatty acids added to the lipid stores of adipocytes are provided by dietary fat (in the form of chylomicrons), with a lesser amount is supplied by VLDL from the liver (see p. 229). 

After the synthesis and release of chylomicrons into the lymphatic circulation, various exchange processes occur by which apolipoproteins, as well as enzymes and other proteins, may be added or removed. These very complex and incompletely under-... 

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. 

LCAT), which catalyzes the synthesis of cholesterol esters (F14, S46, S59) apoA-II, which activates hepatic triglyceride lipase (J2) and apoC-II, which activates lipoprotein lipase, responsible for the hydrolysis of triglycerides in chylomicrons and VLDL (H20, L5). Their mode of action is considered in Section 4 when the individual apolipoproteins are discussed. 

---