Apolipoprotein endoplasmic reticulum

Proteins embedded in the shell of lipoproteins. They serve as scaffold for assembly of the lipoprotein particle in the endoplasmic reticulum. In addition, they control metabolism of lipoproteins in the circulation by interaction with enzymes such as lipases. Finally, apolipoproteins determine cellular uptake of the particles by interaction with specific lipoprotein receptors expressed on the surface of target cells. 

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.

SADP or sulfo-SADP also have been used to study the phenylalanine-methionine-arginine-phenylalanine-amide-activated sodium channel (Coscoy et al., 1998), various apolipoprotein E isoforms (Mann et al., 1995), the high-affinity phenylalkylamine Ca2+ antagonist binding protein from guinea pig (Moebius et al., 1994), the interaction of non-histone proteins with nucleosome core particles (Reeves and Nissen, 1993), and the interactions among cytochromes P-450 in the endoplasmic reticulum (Alston et al., 1991). See Chapter 28 for methods of using photoreactive heterobifunctional crosslinkers to study protein interactions. 

The mixture of lipids moves to the endoplasmic reticulum, where fatty acyl CoA synthetase converts free fatty acids into their activated CoA derivatives. Fatty acyl CoAs are then used to produce triacylglycerols, cholesteryl esters, and phospholipids. These, together with the fat-soluble vitamins (A, D, E, and K) and a single protein (apolipoprotein B-48), form a chylomicron, which is secreted into the lymphatic system and carried to the blood. 

Phung.T. I.., Rod cone, A Jensen, K., Sparks, C, and Sparks,]. D. (1997). Phosphoinositldc 3-kinase activity Ls nsKCSSary for insulin-dependent inhibition of apolipoprOtein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum. /. Biof. Cheof, 271, 30693-3(17112. 

Sarah G., Guo, L., Fisher, E.A., and Brodsky, J.L. Protein disulfide isomerases contribute differentially to the endoplasmic reticulum-associated degradation of apolipoprotein B and other substrates Mol. Biol. Cell. 2012 23(4) 520-532. 

Fatty liver developed in rats fed a diet containing orotic acid is characterized by the deposition of droplets of triglycerides in the tubules of the endoplasmic reticulum [297,298]. The reticulum breaks down into individual vesicles which contain lipid droplets 0.2-0.S im in diameter which accumulate the apolipoproteins of low and very low density lipoproteins. The liver otherwise appears to be functionally normal, unlike that of animals receiving other lipotrophic agents. The administration of orotic acid has a specific effect on lipoprotein synthesis without overall inhibition of protein synthesis. The effect is selective for hepatic but not intestinal P-lipoprotein production and triglyceride transport [299]. 

The interaction of HDL with the lipid droplets has been further investigated by morphological methods (Fig. 3). Upon lipid accumulation in the macrophage, an intimate contact between the endoplasmic reticulum (ER) and the margin of the lipid droplet can be observed. At the site of contact, due to the induction of phospholipid and apolipoprotein synthesis, lamellar bodies are formed which are surrounded by a newly synthesized membrane. These lamellar bodies consist of free cholesterol, phospholipids, and apolipoproteins including Apo E. From these lamellar bodies, HDL take up cholesterol, Apo E, and phosphoUpids on their route through the cell (Fig. 3b). In the absence of HDL, the lamellar bodies which originate from cytoplasmic lipid droplets, cannot be secreted from the cell. 

Several apoproteins are present in the surface layer apoAi (15-35%) apoA4 (10%) apoB (10%) the apoC group (45-50%) and apoE (5%). The A group apolipoproteins are synthesized on the endoplasmic reticulum of the intestinal epithelial cells, whereas apoC and apoB are acquired from other lipoproteins once the chylomicrons have entered the blood. 

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