Lipoprotein lipase and

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. 

The answer is d, (Katzung, pp 589-590.) Only gemfibrozil acts to lower triglycerides, probably because of increased lipolysis by lipoprotein lipase and decreased lipolysis inside adipocytes, causing a net movement of triglycerides into the cell. 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

Selected entries from Methods in Enzymology [vol, page(s)] Detergent-resistant phospholipase Ai from Escherichia coll membranes, 197, 309 phospholipase Ai activity of guinea pig pancreatic lipase, 197, 316 purification of rat kidney lysosomal phospholipase Ai, 197, 325 purification and substrate specificity of rat hepatic lipase, 197, 331 human postheparin plasma lipoprotein lipase and hepatic triglyceride lipase, 197, 339 phospholipase activity of milk lipoprotein lipase, 197, 345. 

Relevant heparin-binding enzymes not involved in the coagulation cascade are, for example, elastase, cathepsin G, superoxide dismutase, lipoprotein lipase and other lipases. The plasma clearing properties of heparin are associated with its binding to lipoprotein lipase and hepatic lipase when the enzymes are released from the surface of endothelial cells [11] and have been studied in view of a potential impact on the regulation of atherosclerosis. 

Mechanism of Action An antihyperlipidemic that enhances synthesis of lipoprotein lipase and reduces triglyceride-rich lipoproteins and VLDLs. Therapeutic Effect Increases VLDL catabolism and reduces total plasma triglyceride levels. Pharmacokinetics Well absorbed from the GI tract. Absorption increased when given with food. Protein binding 99%. Rapidly metabolized in the liver to active metabolite. Excreted primarily in urine lesser amount in feces. Not removed by hemodialysis. Half-life 20 hr. 

Blache D, Bouthillier D, Davignon J (1983) Simple, reproducible procedure for selective measurement of lipoprotein lipase and hepatic lipase. Clin Chem 29 154-158 Bodamer OA, Bercovich D, Schlabach M, Ballantyne C, Zoch D, Beaudet AL (2002) Use of denaturing HPLC to provide efficient detection of mutations causing familial hypercholesterolemia. Clin Chem 48 1913-1918... 

Fojo SS, Brewer HB (1992) Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II. J Intern Med 231 669-677... 

Reina M, Brunzell JD, Deeb SS (1992) Molecular basis of familial chylomicronemia muta-tions in the lipoprotein lipase and apolipoprotein C-II genes. J Lipid Res 33 1823-1832... 

HDL is a reservoir of apolipoproteins HDL particles serve as a circulating reservoir of apo C-ll (the apolipoprotein that is transferred to VLDL and chylomicrons, and is an activator of lipoprotein lipase), and apo E (the apolipoprotein required for the receptor-mediated endocytosis of IDLs and chylomicron remnants). 

Castberg, H. B., Egelrud, T., Solberg, P. and Olivecrona, T. 1975A. Lipases in bovine milk and the relationship between the lipoprotein lipase and tributyrate hydrolysing activities in cream and skim-milk. J. Dairy Res. 42, 255-266. 

Milk is clarified by high-speed centrifugation to remove extraneous matter held in suspension. Clarification occurs prior to heat treatment of the milk to prevent dissolution of the extraneous matter. Although clarification removes somatic cells, the elevated levels of lipoprotein lipase activators and plasmin that may be associated with increased numbers of white blood cells in the milk are not eliminated. Therefore, increased lipolysis of milk fat by lipoprotein lipase and proteolysis of casein by plasmin may not be deterred. 

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... 

As the lipoproteins are depleted of triacylglycerol, the particles become smaller. Some of the surface molecules (apoproteins, phospholipids) are transferred to HDL. In the rat, remnants that result from chylomicron catabolism are removed by the liver. The uptake of remnant VLDL also occurs, but much of the triacylglycerol is further degraded by lipoprotein lipase to give the intermediate-density lipoprotein (IDL). This particle is converted into LDL via the action of lipoprotein lipase and enriched in cholesteryl ester via transfer from HDL by the cholesteryl ester transfer protein. The half-life for clearance of chylomicrons from plasma of humans is 4-5 min. Patients with the inherited disease, lipoprotein lipase deficiency, clear chylomicrons from the plasma very slowly. When on a normal diet, the blood from these patients looks like tomato soup. A very-low-fat diet greatly relieves this problem. 

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,... 

Paradis E., Clavel S., Julien P., Murthy M. R. V., de Bilbao F., Arsenijevic D., Giannakopoulos P., Vallet P., and Richard D. (2004). Lipoprotein lipase and endothelial lipase expression in mouse brain regional distribution and selective induction following kainic acid-induced lesion and focal cerebral ischemia. Neurobiol. Dis. 15 312-325. 

I.J. Goldberg, Lipoprotein lipase and lipolysis central roles in lipoprotein metabolism and atherogenesis, J. Lipid Res. 37 (1996) 693-707. 

Figure 3 Function of CETP, LPL (lipoprotein lipase) and HTGL (hepatic triglyceride...

To 2.0 ml of Amberlite XAD 7 was added 2.0 ml of a 0.05 M phosphoric acid buffer (pH 7.0) having dissolved therein 20 mg of lipoprotein lipase, and the system was allowed to stand at room temperature for 18 hours to thereby adsorb the enzyme onto the resin. The resin was filtered. A solution of 250 mg of 3,5-dinitrobenzoyl derivative of ()-3-acetoxymethyl-7,8-difluoro-2,3-dihydro-4H-[l,4]benzoxazine as a substrate in 25 ml of a mixed solvent of benzene and n-hexane (4 1 by volume) was added to the resin, followed by... 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

N7. Nicoll, A., and Lewis, B., Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism In vivo and in vitro studies in man. Eur. J. Clin. Invest. 10, 487-495 (1980). 

R6. Reardon, M. F.,. Sakai, H., and Steiner, G., Roles of lipoprotein lipase and hepatic triglyceride lipase in the catabolism in vivo of triglyceride-rich lipoproteins. Arteriosclerosis 2, 396-402 (1982). 

In human adipose tissue, palmitoyl-CoA is usually used in the first glycerol-3-phosphate acylation reaction. The next two acyl residues are normally unsaturated fatty acids oleic acid and, less commonly, linoleic acid. Triglyceride biosynthesis is stimulated by insulin, most likely via its activation of lipoprotein lipase and its activity in moving glucose into the cells. 

Zinder, O., Mendelson, C.R., Blanchette-Mackie, E.J., Scow, R.O. 1976. Lipoprotein lipase and uptake of chylomicron triacylglycerol and cholesterol by perfused rat mammary tissue. Biochim. Biophys. Acta 431, 526-537. 

Human milk differs from cows milk in that it contains two lipases, a lipoprotein lipase and a bile salt-stimulated lipase. The ability of the latter to cause considerable hydrolysis of ingested milk lipids has important nutritional implications. 

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