Lipoproteins triacylglycerol

High density lipoprotein (HDL) (a-lipoprotein) Triacylglycerols, phospholipids, cholesterol 75... 

HDL TAKES PART IN BOTH LIPOPROTEIN TRIACYLGLYCEROL CHOLESTEROL METABOLISM... 

Adipose tissue Storage and breakdown of triacylglyc-erol Esterification of fatty acids and lipolysis lipogenesis Glucose, lipoprotein triacylglycerol Free fatty acids, glycerol Lipoprotein lipase, hormone-sensitive lipase... 

Figure 2.1. Model of linoleic acid transport from intestine to milk. Incorporation into intestinal lipoprotein triacylglycerols accounted for 51% of absorbed 14C linoleic acid of this 76% was incorporated directly into milk whereas 10% was incorporated into milk after cycling through other metabolic pool(s). Adapted from Palmquist and Mattos (1978).

N. Hilaire, A. Negre-Salvayre, and R. Salvayre, Cellular uptake and catabolism of high-density-lipoprotein triacylglycerols in human cultured fibroblasts degradation block in neutral lipid storage disease, Biochem. J., 1994, 297, 467-473. 

D. Wiggins and G.E. Gibbons, Origin of hepatic very-low-density lipoprotein triacylglycerol the contribution of cellular phospholipid, Biochem. J., 1996, 320, 673-679. 

Lipoprotein Triacylglycerol Phospholipid Free Cholesterol Cholesterol Ester Protein... 

Fatty acids are transported between organs either as unesterified fatty acids complexed to serum albumin or in the form of triacylglycerols associated with lipoproteins. Triacylglycerols are hydrolyzed outside cells by lipoprotein lipase to yield free fatty acids (Chapter 19). The mechanism by which fatty acids enter cells remains poorly understood despite a number of studies performed with isolated cells from various tissues [4]. Kinetic evidence has been obtained for both a saturable and a non-saturable uptake of fatty acids. The saturable uptake predominates at nanomolar concentrations of fatty acids and is thought to be mediated, or assisted, by proteins. In contrast, the non-saturable uptake that is effective at higher concentrations of fatty acids has been attributed to passive diffusion of fatty acids across the membrane. Several suspected fatty acid transport proteins have been identified [5]. Although their specific functions in fatty acid uptake remain to be elucidated, these proteins may assist in the desorption of fatty acids from albumin and/or function in uptake coupled to the esterification of fatty acids with CoA, in a process referred to as vectorial acylation. 

Trace amounts of many other proteins are recovered in purified fractions of plasma lipoproteins. Some, like albumin, have plausible functions both at the lipoprotein surface [binding unesterified fatty acids newly generated from lipoprotein triacylglycerol (TG)] and in free solution to ensure osmotic balance between cells and their surroundings. Blood-clotting proteins are present in low amounts in TG-rich lipoproteins, but it is not clear that they play a unique biological role in lipoproteins. Many lipoprotein-associated proteins have no known function in lipid transport. 

Abbreviations LPL, lipoprotein lipase LDL, low-density lipoprotein HDL, high-density lipoprotein triacylglycerols, triglyoerides PPAR, peroxisome proliferators-aoti-vated reoeptor (the Table is adapted from Ciroulation 2002 106 3145-3457). 

The lipoprotein triacylglycerols in chylomicrons and VLDL are hydrolyzed to fatty acids and glycerol by lipoprotein lipase (LPL), an enzyme attached to endothelial cells of capillaries in muscle and adipose tissue. The enzyme found in muscle, particularly heart muscle, has a low for these blood lipoproteins. Therefore, it acts even when these lipoproteins are present at very low concentrations in the blood. The fatty acids enter muscle cells and are oxidized for energy. The enzyme found in adipose tissue has a higher and is most active after a meal when blood lipoprotein levels are elevated. 

Owen, M.R., Corstorphine, C.C. Zammit, V.A. (1997) Biochem. J., 323, 17-21. Overt and latent activities of diacylglycerol acyltransferase in rat liver microsomes possible roles in very-low-density lipoprotein triacylglycerol secretion. 

Yang, L.-Y., Kuksis, A., Myher, J. J. and Steiner, G. (1996) Contribution of de novo fatty acid synthesis to very low density lipoprotein triacylglycerols evidence from mass isotopomer distribution analysis of fatty acids synthesised from pH6] ethanol. J. Lipid Res., 37, 262-74. 

Not only are 9c, t and 10t,12c-18 2 isomers metabolized differently, but they also have distinct effects on the metabolism of other fatty acids. Although both isomers resulted in a decrease in the level of arachidonic acid in liver phospholipids of rats, only the 10t,12c-18 2 induced an increase in the C22 polyunsaturated fatty acid in the hver hpids (2). Similarly, CLA supplementation (as a mixture or the 10f,12c isomer) decreased the 18 2n-6 content in hver phospholipids of hamsters (6). At the same time, docosahexaenoic acid was also decreased and a similar pattern was observed in low density lipoprotein-triacylglycerols. Feeding a mixture of CLA for 42 d induced an inaease in the long-chain n-3 fatty acids in rat liver, i.e., 22 5 and 22 6 (7). 

FIGURE 24.3 (a) A duct at the junction of the pancreas and duodenum secretes pancreatic juice into the duodenum, the first portion of the small intestine, (b) Hydrolysis of triacylglycerols by pancreatic and intestinal lipases. Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions. Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases. Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into lipoprotein aggregates termed chylomicrons (discussed in Chapter 25). 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

Increased lipid synthesis/inhibi-tion of lipolysis Activation of lipoprotein lipase (LPL)/induc-tion of fatty acid synthase (FAS)/inactivation of hormone sensitive lipase (HSL) Facilitated uptake of fatty acids by LPL-dependent hydrolysis of triacylglycerol from circulating lipoproteins. Increased lipid synthesis through Akt-mediated FAS-expression. Inhibition of lipolysis by preventing cAMP-dependent activation of HSL (insulin-dependent activation of phosphodiesterases )... 

Figure 15-6. Transport and fate of major lipid substrates and metabolites. (FFA, free fatty acids LPL, lipoprotein lipase MG, monoacylglycerol TG, triacylglycerol VLDL, very low density lipoprotein.)...

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure 25-1). These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane (Chapter 14). The protein moiety of a lipoprotein is known as an apo-lipoprotein or apoprotein, constituting nearly 70% of some HDL and as litde as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other hpoproteins. 

Figure 2S-1. Generalized structure of a plasma lipoprotein. The similarities with the structure of the plasma membrane are to be noted. Small amounts of cholesteryl ester and triacylglycerol are to be found in the surface layer and a little free cholesterol in the core.

TRIACYLGLYCEROL IS TRANSPORTED FROM THE INTESTINES IN CHYLOMICRONS FROM THE LIVER IN VERY LOW DENSITY LIPOPROTEINS... 

Triacylglycerols of Chylomicrons VLDL Are Hydrolyzed by Lipoprotein Lipase... 

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.

Reaction with lipoprotein lipase results in the loss of approximately 90% of the triacylglycerol of chylomicrons and in the loss of apo C (which remrns to HDL) but not apo E, which is retained. The resulting chy-lotnicron remnant is about half the diameter of the parent chylomicron and is relatively enriched in cholesterol and cholesteryl esters because of the loss of triacylglycerol (Figure 25-3). Similar changes occur to VLDL, with the formation of VLDL remnants or IDL (intermediate-density lipoprotein) (Figure 25-4). 

Figure 25-4. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL). (A, apolipoprotein A B-100, apolipoprotein B-100 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylglycerol IDL, intermediate-density lipoprotein C, cholesterol and cholesteryl ester P, phospholipid.) Only the predominant lipids are shown. It is possible that some IDL is also metabolized via the LRP.

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

The second type of fatty liver is usually due to a metabolic block in the production of plasma lipoproteins, thus allowing triacylglycerol to accumulate. Theoretically, the lesion may be due to (1) a block in apolipoprotein synthesis, (2) a block in the synthesis of the lipoprotein from lipid and apolipoprotein, (3) a failure in provision of phospholipids that are found in lipoproteins, or (4) a failure in the secretory mechanism itself. 

Figure 25-6. The synthesis of very low density lipoprotein (VLDL) in the liver and the possible loci of action of factors causing accumulation of triacylglycerol and a fatty liver. (EFA, essential fatty acids FFA, free fatty acids ...

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

Four major groups of lipoproteins are recognized Chylomicrons transport lipids resulting from digestion and absorption. Very low density lipoproteins (VLDL) transport triacylglycerol from the liver. Low-density lipoproteins (LDL) deliver cholesterol to the tissues, and high-density lipoproteins (HDL) remove cholesterol from the tissues in the process known as reverse cholesterol transport. 

Chylomicrons and VLDL are metabolized by hydrolysis of their triacylglycerol, and lipoprotein remnants are left in the circulation. These are taken up by liver, but some of the remnants (IDL) resulting from VLDL form LDL which is taken up by the liver and other tissues via the LDL receptor. 

---