Endoplasmic reticulum, rough lipoprotein

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.

Very low density lipoproteins (VLDL) are synthesized in the liver cell at the contact area of the smooth and rough endoplasmic reticulum and, to a very minor degree, in the mucosa of the small intestine. They have a particle size of 30-80 nm and consist of 90% lipids and 8 — 13% proteins. Their density is <1.006 g/ml. The predominant apohpoproteins are B, C III, and E. They are designated as pre-beta lipoproteins on the basis of their electrophoretic migration. The main function of VLDL is the transport of triglycerides of endogenous origin, (s. fig. 3.8)... 

A. Cotranslational Lipoprotein Formation in Rough Endoplasmic Reticulum... 

ApoB is synthesized in the rough endoplasmic reticulum (RER), where it was first detected by immunoelectron microscopy (Alexander et al., 1976). In vitro translation experiments utilizing rabbit reticulocytes or wheat germ extracts and dog pancreatic microsomes have shown that the apoB is inserted into the lumen of the ER (Chuck and Lingappa, 1992), and that once the insertion is completed, the apoB appears to be associated with the inner leaflet of the bilayer (Pease et al., 1991). In the in vitro translation systems employed in these experiments, the dog pancreatic microsomes were probably not synthesizing appreciable quantities of phospholipid or triglycerides, and therefore did not incorporate apoB into lipoproteins. 

After partial hydrolysis in the gut, dietary fatty acids, monoacylglycerols, phospholipids, and cholesterol are absorbed into the mucosal enterocytes lining the small intestine (Chapter 12). Once within the cell, the lipids are reesterified and form a lipid droplet within the lumen of the smooth endoplasmic reticulum. These droplets consists of triacylglycerol and small amounts of cholesteryl esters and are stabilized by a surface film of phospholipid. At the junction of the smooth and the rough endoplasmic reticulum, the droplet acquires apoproteins B-48, A-I, A-II, and A-IV, which are produced in the lumen of the rough endoplasmic reticulum in the same way as other proteins bound for export. The lipoprotein particle is then transported to the Golgi stacks where further processing yields chylomicrons, which are secreted into the lymph and then enter the blood circulation at the thoracic duct. 

In most eukaryotic cells two major classes of ribosomes exist attached ribosomes and free ribosomes. The attached ribosomes are bound to an extensive cytoplasmic network of lipoprotein membranes called the endoplasmic reticulum. The rough endoplasmic reticulum consists of bound ribosomes the smooth endoplasmic reticulum is devoid of ribosomes. There is no structural difference between a... 

Fig. 32.10. Formation and secretion of chylomicrons. The triacylglycerol is produced in the smooth endoplasmic reticulum (SER) of intestinal epithelial cells from the digestive products, fatty acids, and 2-monoacylglycerols. The protein is synthesized in the rough endoplasmic reticulum (RER). The major apoprotein in chylomicrons is B-48. Assembly of the lipoproteins occurs in both the ER and the Golgi complex.

The protein component of the lipoproteins is synthesized on the rough endoplasmic reticulum. Lipids, which are synthesized in the smooth endoplasmic reticulum, are complexed with the proteins to form the chylomicrons (see Fig. 32.10). 

Dixoa J.L., Chattapadhyay, R., Huima, T., Redmaa C.M. Baneijee, D. (1992). Biosynthesis of lipoprotein location of nascent ApoAI and ApoB in the rough endoplasmic reticulum of chicken hepatocytes.j. CellBiol, 117,1161-9. 

Swift, L.L. (1995) J. Lipid Res., 26, 395-406. Assembly of very low density lipoproteins in rat liver a study of nascent particles recovered from the rough endoplasmic reticulum. 

Chylomicrons are assembled from TAG in the intestine. Their apoprotein components are synthesized and modified in the rough endoplasmic reticulum but the chylomicron itself is assembled in the Golgi. Chylomicrons are synthesized with a unique apoB48 on their surface, but also acquire apoE and apoCII once they are in the circulation. The apoCII allows the chylomicrons to interact with lipoprotein in the capillaries of the adipose tissue to release most of the triglyceride. Lipoprotein lipase hydrolyses chylomicron TAG to monoacylglycerol, FA and glycerol so that they can enter the adipocyte where TAG is re-synthesized and stored. Chylomicron remnants containing cholesterol and fat soluble vitamins are removed from the circulation by the liver. 

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