Lipoprotein esterase

Serum cholesterol. Most cholesterol is carried in the blood by low density lipoprotein (LDL, Tables 21-1,21-2), which delivers the cholesteryl esters directly to cells that need cholesterol. Both a 74-kDa cholesteryl ester transfer protein193-1953 and a phospholipid transfer protein196 1963 are also involved in this process. Cholesterol esterases, which release free cholesterol, may act both on lipoproteins and on pancreatic secretions.197-199... 

Fig. 3. Steroidogenic pathway in granulosa cells. A. Lipoprotein in receptors. B. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase). C. Acyl-coenzyme A (cholesterol acyl transferase). D. Cholesterol esterase. E. Cholesterol transport to the mitochondria. F. Cholesterol side-chain cleavage enzymes (phospholipid membrane environment and enzyme levels). G. 3/3-Hydroxysteroid dehydrogenase (3/3-HSD). H. 20a-Hydroxysteroid dehydrogenase (20a-HSD). I. Aromatases.

E. Neither hormone sensitive lipase nor lipoprotein lipase is a digestive enzyme. The patient s symptoms are consistent with an inability to absorb triglycerides, which wonld eliminate cholesteryl esterase from consideration. Since the patient did not have any problems while being breast-fed, then the most likely enzyme to be deficient is pancreatic lipase, since gastric lipase is most active on short chain triglycerides, such as those that are found in breast milk. 

A series of cyanohydrin acetates with an e.e. up to 98% has been prepared by enzymatic hydrolysis of their racemic acetates in the presence of an esterase from Pseudomonas spJ137]. Lipoprotein lipase from Pseudomonas sp. catalysed irreversible transesterification using enol esters was applied to the resolution of different aromatic cyanohydrins[138> 139). 

Figure 18-16 depicts a model for the selective uptake of cholesteryl esters by a cell-surface receptor called SR-BI (scavenger receptor, class B, type I). SR-BI binds HDL, LDL, and VLDL and can mediate selective uptake from all of these lipoproteins. The detailed mechanism of selective llpid uptake has not yet been elucidated, but It may entail hemifuslon of the outer phospholipid monolayer of the lipoprotein and the exoplasmic leaflet of the plasma membrane. The cholesteryl esters Initially enter the hydrophobic center of the plasma membrane, are subsequently transferred across the Inner leaflet, and are eventually hydrolyzed by cytosolic, not lysosomal, cholesteryl esterases. The llpid-depleted particles remaining after llpid transfer dissociate from SR-BI and return to the circulation they can then extract more phospholipid and cholesterol from other cells by means of the ABCAl protein or other cell-surface transport proteins (see Figure 18-13c). Eventually, small llpid-depleted HDL particles circulating In the bloodstream are filtered out by the kidney and bind to a different receptor on renal epithelial cells. After these particles have been Internalized by receptor-mediated endocytosis, they are degraded by lysosomes.

Zschornig, O., Pietsch, M., Slip. R., Schiller, J. and Gtitschow, M., Cholesterol esterase action on human high density lipoproteins and inhibition studies detection by MALDI-TOF MS, J Lipid Res, 46 (2005) 803-811. 

Several sources of cellular cholesterol contribute to RCT. Part of the process of RCT reflects peripheral (extra-hepatic) cholesterol synthesis. Despite the down-regulation of cholesterol synthesis mediated by the LDL receptor via the delivery of LDL, a considerable amount of sterol is made in peripheral tissues. The importance of this source of cholesterol to homeostasis may be as great as that of dietary cholesterol in many individuals. After hydrolysis of LDL-CE by cellular cholesterol esterases, this cholesterol is made available for recycling to the cell surface and can be recovered there by apo A1 for incorporation into HDLs. Cholesterol is also available from VLDLs, LDLs, and chylomicrons directly internalized by peripheral cells. Cholesterol from HDLs bypasses the lysosomal pathway and becomes part of recycling endosomes that return to the cell surface. Some of the cholesterol recovered on HDLs originates from blood cells. Finally, some cholesterol is transferred directly to other lipoproteins from chylomicrons, VLDLs, and LDLs, without entering the cell. 

The major bioactive products of fatty acid metabolism relevant to atherosclerosis are those that result from enzymatic or non-enzymatic oxidation of polyunsaturated long-chain fatty acids. In most cases, these fatty acids are derived from phospholipase A2-mediated hydrolysis of phospholipids (Chapter 11) in cellular membranes or lipoproteins, or from lysosomal hydrolysis of lipoproteins after internalization by lesional cells. In particular, arachidonic acid is released from cellular membrane phospholipids by arachidonic acid-selective cytosolic phospholipase Aj. In addition, there is evidence that group II secretory phospholipase Aj (Chapter 11) hydrolyzes extracellular lesional lipoproteins, and lysosomal phospholipases and cholesterol esterase release fatty acids from the phospholipids and CE of internalized lipoproteins. Indeed, Goldstein and Brown surmised that at least one aspect of the atherogenicity of LDL may lie in its ability to deliver unsaturated fatty acids, in the form of phospholipids and CE, to lesions (J.L. Goldstein and M.S. Brown, 2001). 

Enzymatic methods are commonly used for this measurement, and many of the current methods use a cholesterol esterase to hydrolyze lipoprotein-cholesteryl esters, followed by further reactions where cholesterol oxidase is linked to a peroxidase-chromogen system (Richmond 1992). Eree cholesterol can be measured by omitting cholesterol esterase of the first reaction step, although many reagent formulations prevent this elimination of the esterase. 

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