Lysosomal acid lipase

Ikeda, S., Nikaido, K., Araki, F K. et al. (2004) Production of recombinant human lysosomal acid lipase in Schizosaccharomyces pombe. development of a fed-batch fermentation and purification process. Journal of... 

Du, H., Heur, M., Witte, D. P., Ameis, D. and Grabowski, G. A. (2002). Lysosomal acid lipase deficiency Correction of lipid storage by adenovirus-mediated gene transfer in mice. Hum. Gene Ther. 13, 1361-1372. 

These vesicles, containing LDL, subsequently fuse with lysosomes, acidic vesicles that carry a wide array of degradative enzymes. The protein component of the LDL is hydrolyzed to free amino acids. The cholesteryl esters in the LDL are hydrolyzed by a lysosomal acid lipase. The LDL receptor itself usually returns unscathed to the plasma membrane. The round-trip time for a receptor is about 10 minutes in its lifetime of about a day, it may bring many LDL particles into the cell. 

Abbreviations GcL, Geotrichum candidum lipase hPL, human pancreatic lipase RmL, Rhizomucor miehei lipase hHL, human hepatic lipase hLPL, human lipoprotein lipase hLAL, human lysosomal acid lipase hGL, human gastric lipase BAL, bile salt-activated lipase HSL, hormone-sensitive lipase CLP, colipase AChE, Torpedo cal omica acetylcholinesterase cDNA, complementary deoxyribonucleic acid VLDL, very low-density lipoprotein IDL, intermediate-density lipoprotein HDL, high-density lipoprotein apoC-II, apolipoprotein C-II. 

Once lipoprotein cholesterol enters the cell, the cholesteryl esters are hydrolyzed by lysosomal acid lipase. The lack or malfunction of this enzyme results in intracellular accumulation of cholesterol esters and produces a clinical disorder known as cholesteryl ester storage disease. 

Roussel, A., Canaan, S., Egloff, M. P., Riviere, M., Dupuis, L, Verger, R. and Cambillau, C. (1999) Crystal structure of human gastric lipase and model of lysosomal acid lipase, two lipolytic enzymes of medical interest. J. Biol. Chem. 274, 16995-17002... 

D. Ameis, M. Merkel, C. Eckerskorn, and H. Greten, Purification, characterization and molecular cloning ofhuman hepatic lysosomal acid lipase, Eur. J. Biochem., 1994, 219, 905-914. 

R.A. Anderson and G.N. Sando, Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl-ester hydrolase. Similarities to gastric and lingual lipases, J. Biol. Chem., 1991, 266, 22479-22484. 

H. Nakagawa, S. Matsubara, M. Kuri-YAMA, H. Yoshidome, J. Fujiyama, H. Yoshida, and M. Osame, Cloning of rat lysosomal acid lipase cDNA and identification of the mutation in the rat model ofWolmaris disease, J. Lipid Res., 1995, 36, 2212-2218. 

The source of these may be the neutral lipid bodies (NLBs) containing triacylglycerol (TAG) and DAG, which are associated with the FVs (Jack-son et al., 2004). The scenario proposed is the double-membrane vesicle produced during cytostomal feeding (see p. 171) has its outer membrane fused with the FV membrane while its inner membrane is degraded by phospholipase C and/or lysosomal acid lipase (and found in the falciparum genome) the breakdown products are assembled into TAG and its precursors serve as promoters of p-hematin formation. 

Large Scale Biology Antigen from cancer cells as personalized cancer vaccines, Aprotinin Alpha-galactosidase, Hematopoietic factors, lysosomal acid lipase 234-238, 239... 

Patients with this autosomal recessive mutation are deficient in the lysosomal acid lipase that hydrolyzes cholesteryl esters and triglycerides derived from plasma lipoproteins [106]. This deficiency results in the accumulation of cholesteryl esters in the lysosomes of all body tissues [16,107]. Wolman syndrome patients usually do not survive the first year of life. 

Cholesteryl ester storage disease is a less severe form of Wolman syndrome in which a residual amount (1-5%) of lysosomal acid lipase activity is expressed [108,109]. Patients with this disease may survive until young adulthood. 

The fate of lipoprotein cholesterol after internalization is a key issue in understanding the biology and pathology of lesional macrophages. After internalization by receptor-mediated endocytosis or phagocytosis, the lipoproteins are delivered to late endosomes or lysosomes, where hydrolysis of proteins and lipids occurs. Most importantly, the large lipoprotein-CE stores are hydrolyzed by a lysosomal enzyme called lysosomal acid lipase. The liberated FC then trafficks to the plasma membrane and other cellular sites [14]. 

Yanagita T, Enomoto N, Kuzuhara S. 1986. Effects of phthalate esters on liver lysosomal acid lipase and acid esterase in vitro. Agric Biol Chem 50 1653-1654. 

Human blood mononuclear leucocyte lysosomal acid lipase (triacylglycerol acylhydrolase, EC... 

Lysosomal acid lipase (EC 3.1.1.13) is a lipolytic enzyme involved in the intracellular metabolism of cholesteryl esters and triacylglycerols derived from plasma lipoproterins (Goldstein et al. 1975). The enzyme is synthesised in a variety of cells, including fibroblasts (Sando and Henke 1982, Sando and Rosenbaum 1985), mononuclear leucocytes... 

Lysosomal acid lipase (LAL) expression is suppressed in monocytes from patients with Lp(a) hyperlipidemia and by purified Lp(a). IL-6 secretion was also induced by purified Lp(a) (453). 

Buechler C, Ullrich H, Aslanidis C, et al. Lipoprotein (a) downregulates lysosomal acid lipase and induces interleukin-6 in human blood monocytes. Biochim Biophys Acta 2003 1642 25-31. 

More general information about the potential role of apoE in cellular lipoprotein uptake has come from studies with cultured cells (e.g., fibroblasts). Such cells manifest surface receptors for LDL that bind apoB, the protein component of LDL. This is followed by receptor-mediated endocytosis, fusion of the endo-cytic vesicles with lysosomes, and LDL degradation within the lysosomes (see Goldstein and Brown, 1979 Brown et al., 1981, for reviews and references). Cholesteryl esters taken into cells in this manner are hydrolyzed by a lysosomal acid lipase. The liberated cholesterol then leaves the lysosome and is used in the cell for membrane synthesis and as a regulator of intracellular cholesterol homeostasis. 

The anatomic sites (subcellularly) and the details of the enzymatic processes involved in the hydrolysis of chylomicron cholesteryl esters newly taken up by the liver have not been fully defined. It is clear that one of the major processes consists of receptor-mediated endocytosis of chylomicron remnants, followed by hydrolysis of cholesteryl esters and other remnant components within lysosomes. In rare genetic diseases characterized by lysosomal acid lipase deficiency (Wol-man s disease and cholesteryl ester storage disease), cholesteryl esters accumulate in liver cells and in other tissues as well [see Assmann and Frederickson (1983) for review and references]. An acid cholesteryl ester hydrolase from rat liver lysosomes has been partially purified and characterized (Brown and Sgoutas, 1980 Van Berkel etal., 1980). Enzymatic activity was found in preparations of both parenchymal and nonparenchymal liver cells (Van Berkel et al., 1980). Hydrolysis of chylomicron cholesteryl esters taken up by isolated rat hepatocytes was inhibited by chloroquine (Florin and Nilsson, 1977), an agent which inhibits the action of acid hydrolases in lysosomes. Finally, there is also evidence that the rate of cholesteryl ester hydrolysis may be limited by the rate at which internalized remnant particles are moved to the presumably lysosomal site of hydrolysis (Nilsson, 1977 Florin and Nilsson, 1977 Cooper and Yu, 1978). 

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