Lipases Lipoprotein lipases

The best-known effect of APOE is the regulation of lipid metabolism (see Fig. 10.13). APOE is a constituent of TG-rich chylomicrons, VLDL particles and their remnants, and a subclass of HDL. In addition to its role in the transport of cholesterol and the metabolism of lipoprotein particles, APOE can be involved in many other physiological and pathological processes, including immunoregu-lation, nerve regeneration, activation of lipolytic enzymes (hepatic lipase, lipoprotein lipase, lecithin cholesterol acyltransferase), ligand for several cell receptors, neuronal homeostasis, and tissue repair (488,490). APOE is essential... 

Enzymes such as proteases, lipases, lipoprotein lipases and proteolytic enzyme derived from the bacterium Streptomyces fradie (known as SEP) is capable of attacking natural keratin hydrolysing some peptide linkages. However, proteases arc-most widely used. 

See also Bile Salts, Pancreatic Lipase, Lipoprotein Lipase, Lipoproteins... 

Plasma triacylglycerols are normally cleared by peripheral lipases (lipoprotein lipase or LPL and hepatic triglyceride lipase or HTGL). Because the activities of both LPL and HTGL are rednced in patients with hepatacellular disease, a relatively high level of plasma triacylglycerols may be found in both acute and chronic hepatitis, in patients with cirrhosis of the liver, and in patients with other diffuse hepatocellular disorders. 

HDL, high density lipoprotein LDL, low density lipoprotein VLDL, very low density lipoprotein TAG, triacylglycerol FA, fatty acid IDL, intermediate density lipoprotein TCA, tricarboxylic acid CM, chylomicron DFIAP, dihydroxyacetone phosphate TAG, triacylglycerol FA, fatty acid ApoB, apoprotein B ApoC, apoprotein C LP lipase, lipoprotein lipase ApoE, apoprotein E... 

Lipoprotein lipase (from bovine skimmed milk) [9004-02-8] [EC 3.1.1.34]. Purified by affinity chromatography on heparin-Sepharose [Shirai et al. Biochim Biophys Acta 665 504 1981]. 

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). 

Lipoproteins in Circulation Are Progressively Degraded by Lipoprotein Lipase... 

Gene activated Lipoprotein lipase fatty acid transporter protein adipocyte fatty acid binding protein acyl-CoA synthetase malic enzyme GLUT-4 glucose transporter phosphoenolpyruvate carboxykinase... 

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 Action of Lipoprotein Lipase Forms Remnant Lipoproteins... 

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). 

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... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Goldberg IJ, Merkel M Lipoprotein lipase physiology, biochemistry and molecular biology. Front Biosci 2001 6 D388. 

Figure 27-1. Metabolic interrelationships between adipose tissue, the liver, and extrahepatic tissues. In extrahepatic tissues such as heart, metabolic fuels are oxidized in the following order of preference (1) ketone bodies, (2) fatty acids, (3) glucose. (LPL, lipoprotein lipase FFA, free fatty acids VLDL, very low density lipoproteins.)...

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

Heart Pumping of blood Aerobic pathways, eg, P-oxidation and citric acid cycle Free fatty acids, lactate, ketone bodies, VLDL and chylomicron triacylglycerol, some glucose Lipoprotein lipase. Respiratory chain well developed. 

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... 

Heparin is an important anticoagulant. It binds with factors IX and XI, but its most important interaction is with plasma antithrombin III (discussed in Chapter 51). Heparin can also bind specifically to lipoprotein lipase present in capillary walls, causing a release of this enzyme into the circulation. 

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