Apolipoprotein B Apo

A variety of clinical studies have demonstrated that elevated levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo B) are associated with... 

Hypercholesterolemia Adjunctive therapy to diet for the reduction of LDL-C, total-C, triglycerides, and apolipoprotein B (apo B) and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types lla and Mb). 

Apolipoprotein B. Apo B is a structural apolipoprotein for chylomicrons, VLDL, and LDL particles. It is synthesized in enteric and hepatic cells. It is important for cholesterol transport to cells via interaction with LDL receptors. Nowadays, it seems its clinical relevance in CSF investigation is near Apo A-I and Apo A-II, but in current studies some varieties can be found (A23, T3). 

Atorvastatin calcium is used as an adjunct to diet to reduce the elevated total-cholesterol, LDL, apolipoprotein B (apo B), and triglyceride (TG) levels, and to increase the HDL-C level in patients with primary hypercholesterolemia and mixed dyslipidemia. The drug is also used for the treatment of patients with an elevated serum TG levels, and for the patients with primary dysbetaliproteinemia, which do not respond adequately to diet. Atorvastatin calcium is also indicated to reduce the total-cholesterol and LDL-C in patients with homozygous familial hypercholesterolemia (e.g., LDL apheresis) [6]. 

Special proteins, called apolipoproteins, are required for handling and transport of lipid droplets. These proteins are synthesized on the ER and enter the lumen of the ER, where they are assembled into large macromolecular structures. The relevant proteins include apolipoprotein A (apo A) and apolipoprotein B (apo B). Apo A and apo B combine with lipid droplets to form structures called chylomicrons, microscopic particles with large cores of lipid coated with a thin shell of protein. The chylomicrons are transferred to secretory vesicles, which migrate through the cytoplasm to the basal membrane of the cell. Here the vesicles fuse with the membrane, resulting in the expulsion of chylomicrons from the cell. (If the vesicles fused with the apical membrane of the enterocyte, the effect would be a futile transfer of the dietary lipids back to the lumen of the small intestine.)... 

Which of the following statements about apolipoprotein B (apo B) are correct ... 

Apochromatic objectives, 16 471 Apocynaceae, alkaloids in, 2 75 Apodization process, 14 227 apo E gene, and LDL level, 5 136 Apoglucose oxidase (apo-GOD), 14 148 Apolipoprotein B deficiencies, 17 652 Apparel, nylon, 19 766 Apparent bypass... 

Tl. Taddei-Peters, W. C., Butman, B. T., Jones, G. R., Venetta, T. M., Macomber, P. F., and Ransom, J. H., Quantification of lipoprotein(a) particles containing various apolipoprotein(a) isoforms by a monoclonal anti apo(a) capture antibody and a polyclonal anti-apolipoprotein B detection antibody sandwich enzyme immunoassay. Clin. Chem. (Winston-Salem, NC) 39, 1382-1389 (1993). 

VLDL) comprising apolipoproteins B and E, combined mainly with triglycerides are secreted from the liver. Apo A is an a globulin and apo B is found in the (3 fraction, thus HDL and LDL are sometimes referred to as a and (3 lipoprotein respectively and VLDL because in separation by electrophoresis at pH 8.6, it runs ahead of LDL is called pre- 3 lipoprotein. 

The liver synthesizes VLDL to transport triglycerides, vitamin E and, to a lesser extent, cholesterol from the hepatocytes to various tissues of the body. Initially, VLDL contain apolipoprotein B-100 (apoB-100), apoE, and the C-apolipoproteins, but receive additional apolipoproteins and cholesterol esters from HDL in the circulation. Following triglyceride hydrolysis by LPL, VLDL remnants, termed IDL, are formed... 

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. 

Release of VLDLs VLDLs are secreted directly into the blood by the liver as nascent VLDL particles containing apolipoprotein B-100. They must obtain apo C-ll and apo E from circulating HDL (see Figure 18.17). As with chylomicrons, apo C-ll is required for activation of lipoprotein lipase. [Note Abetalipoproteinemia is a rare hypolipoproteinemia caused by a defect in triacylglycerol transfer protein, leading to an inability to load apo B with lipid. As a consequence, no chylomicrons or VLDLs are formed, and tria-cylglycerols accumulate in the liver and intestine.]... 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily triacylglycerol), plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs. This makes the chylomicrons functional. 

Chylomicrons are triglyceride rich and contain apolipoprotein B-48 and the A types. The latter are synthesized in the intestinal tract cells. Additional apoproteins are transferred to the chylomicrons from HDL in circulation the apoE and apoC types. Their site of synthesis is the liver. The chylomicrons are subject to degradation by lipoprotein lipase in the peripheral tissue, especially adipose tissue. Lipoprotein lipase activity is increased by increased blood insulin levels. This enzyme is extracellular, attached to the capillary endothelial cells, and activated by ApoC-II, which is present in the chylomicrons. Lipoprotein lipase causes the hydrolysis of triglycerides, thus decreasing chylomicron size... 

Triacylglycerols and cholesterol are exported from the liver as nascent VLDL complexes, destined primarily to muscle and adipose tissues. The VLDL complex contains apolipoprotein B-lOO and acquires C-I, C-II, C-III and E from circulating HDL complexes. Fatty acids are released from VLDLs in the same way as chylomicrons, through the action of LPL. This action, coupled to a loss of certain apoproteins (the apo-Cs), converts VLDLs to intermediate-density lipoproteins (IDLs), also termed VLDL remnants. The apo-Cs are transferred to HDLs. The predominant remaining proteins are apo-B-100 and apo-E. Further loss of triacylglycerols converts IDLs to LDLs. 

Figure 5.6 General scheme of lipoprotein metabolism. Triacylglycerols and cholesterol are exported from the liver in VLDLs, containing apolipoprotein B-lOO they further acquire apo-C-I, II, III and apo-E from circulating HDL. Apo-C-II activates lipoprotein lipase to remove fatty acids from VLDLs. As triacylglycerols are removed, VLDLs transform to IDEs and finally LDLs. LDLs are the main vehicle for transfer of cholesterol to the tissues uptake of LDL occurs primarily in the liver through LDL-receptor-mediated endocytosis, which requires the presence of apo-B-100. HDLs are synthesised essentially devoid of cholesterol or triacylglycerol and provide a circulating source of apo-C-I, II and apo-E. HDLs gradually accumulate cholesteryl esters, eventually returning these to the liver, mediated by an apo-A-I receptor this is referred to as reverse cholesterol transport. ...

Aldehyde-protein adducts and hydroxyl radicals also stimulate immunological responses directed against the specific modifications of proteins. High antibody titres have been observed from patients with severe alcoholic liver disease, particularly IgA and IgG autoantibodies. Such antibodies have considerable specificity towards aldehyde-lysine residues. Alcohol consumption markedly increases the hepatic output of very low-density lipoprotein (VLDL), but decreases the low-density lipoprotein (LDL) levels and apolipoprotein B. Ethylation of apo-B-lysine renders LDL immunogenic and accelerates its clearance. Alcoholics have been shown to develop acetaldehyde adducts in apo-B-containing lipoproteins, particularly VLDL. 

RNA editing. A shortened version (apo B-48) of apolipoprotein B is formed by the intestine, whereas the full-length protein (apo B-lOO) is synthesized by the liver. A glutamine codon (CAA) is changed into a stop codon. Propose a simple mechanism for this change. 

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