Lipoprotein lipases structure

ApoC-II is expressed in liver and intestine, and both the neural retina and RPE (Li et al., 2006). In contrast to ApoC-I, it can function as an activator of lipoprotein lipase. Similar to ApoA-I, ApoA-II, and ApoE, in the absence of lipid to stabilize its structure, ApoC-II forms amyloid assemblies. 

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. 

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. 

Wang C.S., Hartsuck, J., McConathy, W.J. (1992) Structure and functional properties of lipoprotein lipase. Biochim. Biophys. Acta 1123, 1-17. 

Twelve reviews cover the structure, synthesis, and metabolism of lipoproteins, regulation of cholesterol synthesis, and the enzymes LCAT and lipoprotein lipase. 

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... 

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

Bengtsson-Olivecrona, G., Olivecrona, T., Jornvall, H. 1986. Lipoprotein lipases from cow, guinea-pig and man. Structural characterization and identification of protease-sensitive internal regions. Eur. J. Biochem. 161, 281-288. 

ApolipoprcHein C ll serves as a ccifactor for lipoprotein lipase. This situation resernbSes that of colipase, which is required for the activity of pancieatic lipase. When chylomicrons or VLDLs pass through the capillaries of an organ, they encounter lipoprotein lipase. About half the fatty acids liberated by the action of this enzyme are taken up by the tissue, whereas the rest remain in the circulation and return bound to albumin) to the liver. Apo C-II is part of the structure of chylomicrons and VLDI,. ... 

Both PL and LPL require cofactors for full expression of activity (CLP and apoC-11, respectively) no such cofactor is necessary for HL. Derewenda and Cambillau (1991) postulated that, in the human lipase gene family of enzymes, the loops of the N-terminal domain, which exhibit the most pronounced variation in their amino acid sequences, may be responsible for conferring specificity with respect to cofactors. The structure of the lipase-procolipase complex (van Tilbeurgh et al., 1992 see above) does not support this hypothesis. However, in the case of LPL the structural basis of its interaction with apoC-11 may be quite different. Wong et al. (1991) and Davis et al. (1992) produced hybrid molecules by interchanging the C-terminal domains between the rat hepatic and lipoprotein lipases. Their HL chimera, made up of the HL N-terminal catalytic domain and the LPL C-terminal fragment, exhibited the salt-resistant catalydc properties characteristic of HL, but was... 

Chylomicrons are triglyceride-rich lipoproteins that are slowly modified during the circulation in blood. The core glyceride structure is hydrolyzed by the lipoprotein lipase. It is by the apolipoprotein-specific receptors that the hepatocytes in the lever consume these remnants (210,211). It had been shown that even... 

VAN Tilbeurgh, H., Roussel, A., La-LOUEL, J.M., and Cambiliau, C. lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray structure consequences for heparin binding and catalysis. J. Biol. Chem., 1994, 269, 4626-4633. 

Ma, K., Cilingiroglu, M., Otvos, J.D., Ballantyne, C.M., Marian, A. J., and Chan, L. Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. Proc. Natl. Acad. Sci. USA,... 

Persson, B., Bentsson-Olivecrona, G., Enerback, S., Olivecrona, T. and Jorn-vall, H. (1989) Structural features of lipoprotein lipase. Lipase family relationships, binding interactions, non-equivalence of lipase cofactors, vitellogenin similarities and functional subdivision of lipoprotein lipase. Eur. J. Biochem. 179,... 

It remains to be established whether manipulation of HDL levels will in itself alter the development of CHD. The components of HDL are derived from different sources. " " HDL (or its precursors) is produced by both the liver and intestine. The structural composition of HDL is regulated by LCAT and lipoprotein lipase. There is also non-enzymatic transfer of apolipoprotein (apo) C between HDL and VLDL, exchange of free... 

This reaction is responsible for formation of most of the cholesteryl ester in plasma. The preferred substrate is phosphatidylcholine, which contains an unsaturated fatty acid residue on the 2-carbon of the glycerol moiety. HDL and LDL are the major sources of the phosphatidylcholine and cholesterol. Apo A-I, which is a part of HDL, is a powerful activator of LCAT. Apo C-I has also been implicated as an activator of this enzyme however, activation may depend on the nature of the phospholipid substrate. LCAT is synthesized in the liver. The plasma level of LCAT is higher in males than in females. The enzyme converts excess free cholesterol to cholesteryl ester with the simultaneous conversion of lecithin to lysolecithin. The products are subsequently removed from circulation. Thus, LCAT plays a significant role in the removal of cholesterol and lecithin from the circulation, similar to the role of lipoprotein lipase in the removal of triacylglycerol contained in chylomicrons and VLDL. Since LCAT regulates the levels of free cholesterol, cholesteryl esters, and phosphatidylcholine in plasma, it may play an important role in maintaining normal membrane structure and fluidity in peripheral tissue cells. 

Templeton, A. R., et al., Cladistic structure within the human lipoprotein lipase gene and its implications for phenotypic association studies [In Process Citation]. Genetics, 2000. 

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