Apoprotein chylomicron metabolism

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

The metabolism of cholesterol in mammals is extremely complex. A summary sketch (fig. 20.24) helps to draw the major metabolic interrelationships together. Cholesterol is biosynthesized from acetate largely in the liver (fig. 20.24a) or taken in through the diet (fig. 20.24b). From the intestine, dietary cholesterol is secreted into the plasma mainly as a component of chylomicrons. The triacylglycerol components of chylomicrons are quickly degraded by lipoprotein lipase, and the remnant particles are removed by the liver. Apoproteins and lipid components of the chylomicrons and remnants appear to exchange with HDL. Cholesterol made in the liver (fig. 20.24a) has several alternative fates. It can be (1) secreted into plasma as a component of VLDL,... 

Figure 19.3 Lipoprotein metabolism in the human being. Details of HDL metabolism have been omitted. LPL, lipoprotein lipase FFA, free fatty acids CM, chylomicrons A-E, apoproteins A-E HDL, LDL, IDL, and VLDL are high-density, low-density, intermediate-density, and very low density lipoproteins. (Reproduced by permission from Staff writers. Heart-liver transplantation in a child with homozygous familial hypercholesterolemia. Nutr Rev 43 274-278, 1985.)...

After its absorption into the intestinal mucosal cell, cholesterol, together with triglycerides, phospholipids, and a number of specific apoproteins, is assembled into a large lipoprotein called the chylomicron (see later section on lipoprotein metabolism, exogenous pathway). One apoprotein component known as apolipoprotein (apo) B-48 is vital to the formation of chylomicrons, and in people with a rare deficiency of apo B-48 synthesis, chylomicron formation, and consequently cholesterol and fat absorption, is severely impaired. Chylomicrons enter the lymphatics, which empty into the thoracic duct and eventually enter the systemic venous circulation at the junction of the left subclavian vein and left internal jugular vein. 

The laws of mass action govern the interactions of lipids and most apoproteins in lipoproteins, so that as the affinities between surface components change dining lipoprotein metabolism, apoproteins may dissociate from one particle and bind to another. In fact, all of the apoproteins, with the possible exception of apoprotein B (apo B), can change their lipoprotein associations. The reason for the unique behavior of apo B remains a mystery. On the basis of their principal transport function, lipoproteins may be divided into two classes according to the composition of their major core lipids. The principal triacylglycerol carriers are chylomicrons and very-low-density lipoproteins (VLDLs), whereas most cholesterol transport occurs via LDLs and HDLs. 

Apart from their operational distinction on the basis of density and lipid composition the plasma lipoprotein classes are also distinguished by the nature of the polypeptides present. The apoprotein species have been characterized and designated family names from A to H. The human plasma lipoprotein apoprotein distribution is shown in Table 12.3. Although the distribution, interchange and metabolism of lipoprotein apoproteins is extremely complicated some overall aspects of the dynamic situation can be discerned (see Schaefer etal, 1978). For example, the apoprotein content of newly synthesized VLDL and chylomicrons changes drastically as these lipoproteins enter the circulation and interact with the other lipoproteins present. Both... 

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