Lipoprotein triacylglycerol hydrolysis

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). 

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 )... 

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... 

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. 

Figure 7.3 The action of lipoprotein lipase in the hydrolysis of triacylglycerol in the blood and the fate of the fatty adds produced. Lipoprotein Lipase is attached to the luminal surface of the capillaries in the tissues that are responsible for removal of triacylglycerol from the bloodstream (e.g. adipose tissue, muscle, lactating mammary gland).

This enzyme [EC 3.1.1.34] (also called clearing factor lipase, diglyceride lipase, and diacylglycerol lipase) catalyzes the hydrolysis of a triacylglycerol to produce a diacylglycerol and a fatty acid anion. This enzyme hydrolyzes triacylglycerols in chylomicrons and in low-density lipoproteins and also acts on diacylglycerols. See also Lipases... 

Hydrolysis of triacylglycerols is catalyzed by lipoprotein lipase, a membrane-bound enzyme located on the endothelium lining the capillary beds of the muscle and adipose tissue. 

Both lipoprotein lipase and the less well understood hepatic lipase are related structurally to pancreatic lipase.42,4213 In addition to hydrolysis of the triacylglycerols, the uptake of materials from lipoproteins probably involves shedding of intact phospholipids, perhaps as liposome-like particles 40... 

Chylomicrons transport dietary triacylglycerol and cholesteryl ester from the intestine to other tissues in the body. Very-low-density lipoprotein functions in a manner similar to the transport of endogenously made lipid from the liver to other tissues. These two types of triacylglycerol-rich particles are initially degraded by the action of lipoprotein lipase, an extracellular enzyme that is most active within the capillaries of adipose tissue, cardiac and skeletal muscle, and the lactating mammary gland. Lipoprotein lipase catalyzes the hydrolysis of triacylglycerols (see fig. 18.3). The enzyme is specifically activated by apoprotein C-II, which... 

Lipoprotein lipase (EC 3.1.1.34) is an enzyme or group of enzymes which catalyze the hydrolysis of the 1(3) ester bond(s) of triacylglycerols and the 1 ester bond of phospholipids. The enzyme plays a central role in lipoprotein metabolism, being responsible in particular for the hydrolysis of chylomicron and VLDL triglycerides and the formation of remnant particles from these lipoproteins. There have been reviews of this enzyme [e.g., (N9, Ql)] and lipoprotein lipase will not be discussed in detail in this review. Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism have also been reviewed (B58, N8) and will not be discussed in detail. 

Deckelbaum, R. J., Hamilton, J. A., Moser, A., Bengtsson-Olivecrona, G., Butbul, E., Carpentier, Y. A., Gutman, A., and Olivecrona, T. (1990), Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein hpase and hepatic lipase Implications for the mechanisms of lipase action, Biochemistry, 29,1136-1142. 

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. 

Lipoprotein lipase is an enzyme found in the capillaries that catalyzes the hydrolysis of triacylglycerols in chylomicrons to glycerol and fatty acids (Figure 18.6, Figure 18.7). Lipoprotein lipase is activated by apoprotein C-II, which is found in all of the lipoprotein complexes except LDLs. Apoprotein C-1 may also be involved in activation of lipoprotein lipase. 

Fatty acids appear in the bloodstream in one of two forms as non-esterified fatty acids (NEFA) or in lipoproteins. NEFA have a very short half-life in the blood. The bulk of circulating NEFA arise from the hydrolysis of triacylglycerols stored within adipose tissue and are released into the bloodstream, where their transport is facilitated by albumin, which has multiple binding sites for fatty acids (Frayn, 2003). Plasma NEFA are destined to be used mainly as energy sources (see Section E.l on fatty acids as fuels). 

In the fed state, in response to the action of insulin (section 10.5) lipoprotein lipase is active at the surface of cells in adipose tissue. It catalyses the hydrolysis of triacylglycerols in chylomicrons, and most of the resultant free fatty acid is taken up by adipose tissue for re-esterification to triacylglycerol for storage. The chylomicron remnants are taken up by the liver, by a process of receptor-mediated endocytosis (section 5.6.2), and most of the residual lipid is secreted, together with triacylglycerol synthesised in the liver, in very low-density lipoproteins (section 5.6.2.2). 

In the fed state, chylomicrons assembled in the small intestine (section 4.3.3.2) and very low-density lipoproteins exported from the liver (section 5.6.2.2) bind to the cell surface, where lipoprotein lipase catalyses hydrolysis of triacylglycerols to glycerol and free fatty acids. 

Activation of lipoprotein lipase at the cell surface. As shown in Table 9.2, lipoprotein lipase has a very short half-life, of the order of 1 hour. In response to insulin acting on adipocytes there is induction of enzyme synthesis. The newly synthesized enzyme then migrates to the surface of the blood vessel endothelial walls, where it binds chylomicrons or VLDL (section 5.6.2) and catalyses the hydrolysis of triacylglycerol. The non-esterified fatty acids are mainly taken up by adipose tissue and used for synthesis of triacylglycerol. 

Lipoproteins can be analysed by their lipid content. For cholesterol, the classical Liebermann-Burchard colour reaction gives a reliable means of quantitation which is amenable to automated methods. Triacylglycerols can be quantitated by fluorescence, a method that depends on the presence of the glycerol moiety. Enzymic methods, however, are most often used in modern laboratories since they are usually more sensitive, have better specificity, need small volumes and mild conditions. They are also well suited to modern methods of automation, often without the need for extraction or hydrolysis. The 1980s have seen dramatic advances in lipid laboratory automation, spurred on by the needs of clinical screening, and... 

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