Lipoprotein lipase, human

Clark AG, Weiss KM, Nickerson DA, Taylor SL, Buchanan A, Stengard J et al. Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase. Am J Hum Genet 1998 63 595— 612. 

Diagnosis of lipoprotein lipase deficiency is based on low or absent enzyme activity with normal human plasma or apolipoprotein C-II, a cofactor of the enzyme. 

Clark, A. G., Weiss, K. M., Nickerson, D. A., Taylor, S. L., Buchanan, A., Stengard, J., Salomaa, V., Virtianen, E., Perola, M., Boerwinkle, E., and Sing, C. F. (1998). Haplo-type structure and population genetic inferences from Nucleotide-sequence variation in human lipoprotein lipase. Am. J. Hum. Genet. 63, 595-612. 

Mitchell RJ, Earl L, Bray P, Fripp YJ, Williams J. DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides. Human Biology 1994 66 38397. 

It, thus, appears that the capacity to catalyze reactions of transesterification and esterification is a characteristic of various hydrolases (Chapt. 3). Apart from the carboxylesterases discussed here, lipoprotein lipase has the capacity to synthesize fatty acid ethyl esters from ethanol and triglycerides, or even fatty acids [127]. Ethanol, 2-chloroethanol, and other primary alcohols serve to esterify endogenous fatty acids and a number of xenobiotic acids [128-130]. In this context, it is interesting to note that the same human liver carboxylesterase was able to catalyze the hydrolysis of cocaine to benzoylecgonine, the transesterification of cocaine, and the ethyl esterification of fatty acids [131]. 

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. 

B7. Brown, W. V., and Baginsky, M. L., Inhibition of lipoprotein lipase by an apoprotein of human very low density lipoprotein. Biochem. Biophys. Res. Cotnmun. 46, 375-381 (1972). 

FI. Fielding, C. J., Human lipoprotein lipase. I. Purification and substrate specificity. Biochim. Biophys. Acta 206, 109-117 (1970). 

Gl. Ganesan, D., and Bradford, R. H., Isolation of apolipoprotein-free lipoprotein lipase from human post-heparin plasma. Biochem. Biophys. Res. Commun. 43, 544-549 (1971). 

H3. Havel, R. J., Shore, V. G., Shore, B., and Bier, D. M., Role of specific glyco-peptides of human serum lipoproteins in the activation of lipoprotein lipase. Circ. Res. 27, 595-600 (1970). 

Partial summary of lipoprotein metabolism in humans. I to VII are sites of action of hypolipidemic drugs. I, stimulation of bile acid and/or cholesterol fecal excretion II, stimulation of lipoprotein lipase activity III, inhibition of VLDL production and secretion IV, inhibition of cholesterol biosynthesis V, stimulation of cholesterol secretion into bile fluid VI, stimulation of cholesterol conversion to bile acids VII, increased plasma clearance of LDL due either to increased LDL receptor activity or altered lipoprotein composition. CHOL, cholesterol IDL, intermediate-density lipoprotein. 

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. 

Topiramate, felbamate, and zonisamide are associated with weight loss. In animals topiramate reduced food intake, but also reduced energy disposition in the absence of reduced intake. In addition, topiramate increased lipoprotein lipase activity in adipose tissue, possibly reflecting enhanced regulatory thermogenesis. In humans and animals topiramate reduces leptin concentrations. With felbamate weight loss is almost always associated with... 

CM and VLDL secreted by intestinal cells and VLDL synthesized and secreted in the liver have similar metabolic fates. After secretion into the blood, newly formed CM and VLDL take up apoprotein (apo-C) from HDL and are subsequently removed from the blood (plasma half-life of less than 1 h in humans [137]) primarily by the action of lipoprotein lipase (LPL). Lipoprotein lipase is situated mainly in the vascular bed of the heart, skeletal muscle, and adipose tissue and catalyzes the breakdown of core TG to monoglycerides and free fatty acids, which are taken up into adjacent cells or recirculated in blood bound to albumin. The activity of LPL in the heart and skeletal muscle is inversely correlated with its activity in adipose tissue and is regulated by various hormones. Thus, in the fasted state, TG in CM and VLDL is preferentially delivered to the heart and skeletal muscle under the influence of adrenaline and glucagon, whereas in the fed state, insulin enhances LPL activity in adipose tissue, resulting in preferential uptake of TG into adipose tissue for storage as fat. 

Nickerson DA, Taylor SL, Weiss KM, Clark AG, Hutchinson RG, Stengard J, Salomaa V, Vartiainen E, Boerwinkle E, Sing CF. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat Genet 1998 19 233-240. 

C6. Chait, A., Iverius, P.-H., and Brunzell, J. D., Lipoprotein lipase secretion by human monocyte-derived macrophages. J. Clin. Invest. 69, 490—493 (1982). 

H18. Havel, R. J., Kotite, L., and Kane, J. P., Isoelecric heterogeneity of the cofactor protein for lipoprotein lipase in human blood plasma. Biochem. Med. 21, 121—138 (1979). 

M7. Mahoney, E. M., Khoo, J. C., and Steinberg, D., Lipoprotein lipase secretion by human monocytes and rabbit alveolar macrophages in culture. Proc. Natl. Acad. Sci. U.S.A. 79, 1639-1642 (1982). 

Ostlund-Lindqvist, A.-M., Gustafson, S., Lindqvist, P., Witztum, J. L., and Little, J. A., Uptake and degradation of human chylomicrons by macrophages in culture. Role of lipoprotein lipase. Arteriosclerosis 3, 433-440 (1983). 

W3. Wang-Iverson, P., Ungar, A., Bliumis, J., Bukberg, P. R., Gibson, J. C., and Brown, W. V., Human monocytes in culture synthesize and secrete lipoprotein lipase. Biochem. Biophys. Res. Commun. 104, 923-928 (1982). 

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.)...

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. 

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. 

There were several new developments during the 1970s. Of particular importance was the purification and characterization of a lipoprotein lipase (LPL) and the acceptance of the postulate that this was the major, if not the only, lipase in cows milk (Olivecrona, 1980). Similarly, the elucidation of the lipase system in human milk as consisting of an LPL and a bile salt-stimulated lipase, and the possible role of the latter in infant nutrition, were noteworthy (Fredrikzon et al, 1978). Also, microbial lipolysis assumed substantial significance with the widespread use of low-temperature storage of raw milk and the recognition that heat-stable lipases produced by psychrotrophic bacteria were a major cause of flavor problems in stored dairy products (Law, 1979). 

Goldberg, I.J., Blaner, W.S., Goodman, D.S. 1986. Immunologic and enzymatic comparisons between human and bovine lipoprotein lipase. Arch. Biochem. Biophys. 244, 580-584. 

Neville, M.C., Waxman, L.J., Jensen, D., Eckel, R.H. 1991. Lipoprotein lipase in human milk compartmentalization and effect of fasting, insulin and glucose. J. Lipid Res. 32, 251-257. 

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